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Sample records for models bearing mutations

  1. A semi-analytical bearing model considering outer race flexibility for model based bearing load monitoring

    Science.gov (United States)

    Kerst, Stijn; Shyrokau, Barys; Holweg, Edward

    2018-05-01

    This paper proposes a novel semi-analytical bearing model addressing flexibility of the bearing outer race structure. It furthermore presents the application of this model in a bearing load condition monitoring approach. The bearing model is developed as current computational low cost bearing models fail to provide an accurate description of the more and more common flexible size and weight optimized bearing designs due to their assumptions of rigidity. In the proposed bearing model raceway flexibility is described by the use of static deformation shapes. The excitation of the deformation shapes is calculated based on the modelled rolling element loads and a Fourier series based compliance approximation. The resulting model is computational low cost and provides an accurate description of the rolling element loads for flexible outer raceway structures. The latter is validated by a simulation-based comparison study with a well-established bearing simulation software tool. An experimental study finally shows the potential of the proposed model in a bearing load monitoring approach.

  2. Modeling and simulation of porous journal bearings in multibody systems

    OpenAIRE

    Buuren, Sietze van

    2013-01-01

    A specific cost-efficient type of plain journal bearing is the porous journal bearing, which possesses a pervious bush that serves as a lubricant reservoir. The current work is concerned with modeling porous journal bearings in multibody systems, for which dynamical models are needed to investigate the bearing’s behavior. Such porous journal bearing models as well as models of elementary rotor-bearing systems including these, were developed and investigated during the course for this work.

  3. Generation of Human-Induced Pluripotent Stem Cells from Wolfram Syndrome Type 2 Patients Bearing the c.103 + 1G>A CISD2 Mutation for Disease Modeling.

    Science.gov (United States)

    La Spada, Alberto; Ntai, Aikaterini; Genovese, Stefano; Rondinelli, Maurizio; De Blasio, Pasquale; Biunno, Ida

    2018-02-15

    Wolfram syndrome (WFS) is a rare autosomal premature aging syndrome that shows signs of diabetes mellitus, optic atrophy, and deafness in addition to central nervous system and endocrine complications. The frequent form of WFS type 1 (WFS1) harbors causative mutations in the WFS1 gene, whereas the rare form or WFS type 2 (WFS2) involves CISD2. Mutations in these two genes are recognized by a subset of variable clinical symptoms and a set of overlapping features. In this study, we report on the generation of stable human-induced pluripotent stem cells (hiPSCs) derived from primary fibroblasts of a previously reported Italian family with CISD2 mutation (c.103 + 1G>A), occurring in the consensus intron 1 splicing site in two sisters, deleting the first exon of the transcript. The generated hiPSCs provide a cell model system to study the mutation's role in the multisystemic clinical disorders previously described and test eventual drug effects on the specific and associated clinical phenotype.

  4. Transient thermal modelling of ball bearing using finite element method

    OpenAIRE

    Sibilli, Thierry; Igie, Uyioghosa

    2017-01-01

    Gas turbines are fitted with rolling element bearings, which transfer loads and supports the shafts. The interaction between the rotating and stationary parts in the bearing causes a conversion of some of the power into heat, influencing the thermal behaviour of the entire bearing chamber. To improve thermal modelling of bearing chambers, this work focused on modelling of the heat generated and dissipated around the bearings, in terms of magnitude and location, and the interaction with the co...

  5. Vibration model of rolling element bearings in a rotor-bearing system for fault diagnosis

    Science.gov (United States)

    Cong, Feiyun; Chen, Jin; Dong, Guangming; Pecht, Michael

    2013-04-01

    Rolling element bearing faults are among the main causes of breakdown in rotating machines. In this paper, a rolling bearing fault model is proposed based on the dynamic load analysis of a rotor-bearing system. The rotor impact factor is taken into consideration in the rolling bearing fault signal model. The defect load on the surface of the bearing is divided into two parts, the alternate load and the determinate load. The vibration response of the proposed fault signal model is investigated and the fault signal calculating equation is derived through dynamic and kinematic analysis. Outer race and inner race fault simulations are realized in the paper. The simulation process includes consideration of several parameters, such as the gravity of the rotor-bearing system, the imbalance of the rotor, and the location of the defect on the surface. The simulation results show that different amplitude contributions of the alternate load and determinate load will cause different envelope spectrum expressions. The rotating frequency sidebands will occur in the envelope spectrum in addition to the fault characteristic frequency. This appearance of sidebands will increase the difficulty of fault recognition in intelligent fault diagnosis. The experiments given in the paper have successfully verified the proposed signal model simulation results. The test rig design of the rotor bearing system simulated several operating conditions: (1) rotor bearing only; (2) rotor bearing with loader added; (3) rotor bearing with loader and rotor disk; and (4) bearing fault simulation without rotor influence. The results of the experiments have verified that the proposed rolling bearing signal model is important to the rolling bearing fault diagnosis of rotor-bearing systems.

  6. Experimental Study and Dynamic Modeling of Metal Rubber Isolating Bearing

    International Nuclear Information System (INIS)

    Zhang, Ke; Zhou, Yanguo; Jiang, Jian

    2015-01-01

    In this paper, dynamic shear mechanical properties of a new metal rubber isolating bearing is tested and studied. The mixed damping model is provided for theoretical modeling of MR isolating bearing, the shear stiffness and damping characteristics of the MR bearing can be analyzed separately and easily discussed, and the mixed damping model is proved to be an rather effective approach. The test results indicate that loading frequency bears little impact over shear property of metal rubber isolating bearing, the total energy consumption of metal rubber isolating bearing increases with the increase in loading amplitude. With the increase in loading amplitude, the stiffness of the isolating bearing will reduce showing its “soft property”; and the type of damping force gradually changes to be close to dry friction. The features of “soft property” and dry friction energy consumption of metal rubber isolating bearing are very useful in practical engineering application. (paper)

  7. Modeling of dynamically loaded hydrodynamic bearings at low Sommerfeld numbers

    DEFF Research Database (Denmark)

    Thomsen, Kim

    and failure risk of rolling element bearings do, however, grow exponentially with the size. Therefore hydrodynamic bearings can prove to be a competitive alternative to the current practice of rolling element bearings and ultimately help reducing the cost and carbon footprint of renewable energy generation....... The challenging main bearing operation conditions in a wind turbine pose a demanding development task for the design of a hydrodynamic bearing. In general these conditions include operation at low Reynolds numbers with frequent start and stop at high loads as well as difficult operating conditions dictated...... by environment and other wind turbine components. In this work a numerical multiphysics bearing model is developed in order to allow for accurate performance prediction of hydrodynamic bearings subjected to the challenging conditions that exist in modern wind turbines. This requires the coupling of several...

  8. Modeling of Tilting-Pad Journal Bearings with Transfer Functions

    Directory of Open Access Journals (Sweden)

    J. A. Vázquez

    2001-01-01

    Full Text Available Tilting-pad journal bearings are widely used to promote stability in modern rotating machinery. However, the dynamics associated with pad motion alters this stabilizing capacity depending on the operating speed of the machine and the bearing geometric parameters, particularly the bearing preload. In modeling the dynamics of the entire rotor-bearing system, the rotor is augmented with a model of the bearings. This model may explicitly include the pad degrees of freedom or may implicitly include them by using dynamic matrix reduction methods. The dynamic reduction models may be represented as a set of polynomials in the eigenvalues of the system used to determine stability. All tilting-pad bearings can then be represented by a fixed size matrix with polynomial elements interacting with the rotor. This paper presents a procedure to calculate the coefficients of polynomials for implicit bearing models. The order of the polynomials changes to reflect the number of pads in the bearings. This results in a very compact and computationally efficient method for fully including the dynamics of tilting-pad bearings or other multiple degrees of freedom components that interact with rotors. The fixed size of the dynamic reduction matrices permits the method to be easily incorporated into rotor dynamic stability codes. A recursive algorithm is developed and presented for calculating the coefficients of the polynomials. The method is applied to stability calculations for a model of a typical industrial compressor.

  9. Experimental Grey Box Model Identification of an Active Gas Bearing

    DEFF Research Database (Denmark)

    Theisen, Lukas Roy Svane; Pierart Vásquez, Fabián Gonzalo; Niemann, Hans Henrik

    2014-01-01

    Gas bearings have inherent dynamics that gives rise to low damping and potential instability at certain rotational speeds. Required damping and stabilization properties can be achieved by active ow control if bearing parameters are known. This paper deals with identifacation of parameters...... in a dynamic model of an active gas bearing and subsequent control loop design. A grey box model is determined based on experiments where piezo actuated valves are used to perturb the journal and hence excite the rotor-bearing system. Such modelling from actuator to output is shown to effciently support...... controller design, in contrast to impact models that focus on resonance dynamics. The identified model is able to accurately reproduce the lateral dynamics of the rotor-bearing system in a desired operating range, in this case around the first two natural frequencies. The identified models are validated...

  10. Hibernating bears as a model for preventing disuse osteoporosis.

    Science.gov (United States)

    Donahue, Seth W; McGee, Meghan E; Harvey, Kristin B; Vaughan, Michael R; Robbins, Charles T

    2006-01-01

    The hibernating bear is an excellent model for disuse osteoporosis in humans because it is a naturally occurring large animal model. Furthermore, bears and humans have similar lower limb skeletal morphology, and bears walk plantigrade like humans. Black bears (Ursus americanus) may not develop disuse osteoporosis during long periods of disuse (i.e. hibernation) because they maintain osteoblastic bone formation during hibernation. As a consequence, bone volume, mineral content, porosity, and strength are not adversely affected by annual periods of disuse. In fact, cortical bone bending strength has been shown to increase with age in hibernating black bears without a significant change in porosity. Other animals require remobilization periods 2-3 times longer than the immobilization period to recover the bone lost during disuse. Our findings support the hypothesis that black bears, which hibernate for as long as 5-7 months annually, have evolved biological mechanisms to mitigate the adverse effects of disuse on bone porosity and strength.

  11. On The Modelling Of Hybrid Aerostatic - Gas Journal Bearings

    DEFF Research Database (Denmark)

    Morosi, Stefano; Santos, Ilmar

    2011-01-01

    modeling for hybrid lubrication of a compressible fluid film journal bearing. Additional forces are generated by injecting pressurized air into the bearing gap through orifices located on the bearing walls. A modified form of the compressible Reynolds equation for active lubrication is derived. By solving......Gas journal bearing have been increasingly adopted in modern turbo-machinery applications, as they meet the demands of operation at higher rotational speeds, in clean environment and great efficiency. Due to the fact that gaseous lubricants, typically air, have much lower viscosity than more...

  12. Modelling of Rotor-gas bearings for Feedback Controller Design

    DEFF Research Database (Denmark)

    Theisen, Lukas Roy Svane; Niemann, Hans Henrik

    2014-01-01

    Controllable rotor-gas bearings are popular oering adaptability, high speed operation, low friction and clean operation. Rotor-gas bearings are however highly sensitive to disturbances due to the low friction of the injected gas. These undesirable damping properties call for controllers, which ca...... and are shown to accurately describe the dynamical behaviour of the rotor-gas bearing. Design of a controller using the identied models is treated and experiments verify the improvement of the damping properties of the rotor-gas bearing.......Controllable rotor-gas bearings are popular oering adaptability, high speed operation, low friction and clean operation. Rotor-gas bearings are however highly sensitive to disturbances due to the low friction of the injected gas. These undesirable damping properties call for controllers, which can...... be designed from suitable models describing the relation from actuator input to measured shaft position. Current state of the art models of controllable gas bearings however do not provide such relation, which calls for alternative strategies. The present contribution discusses the challenges for feedback...

  13. On spatial mutation-selection models

    Energy Technology Data Exchange (ETDEWEB)

    Kondratiev, Yuri, E-mail: kondrat@math.uni-bielefeld.de [Fakultät für Mathematik, Universität Bielefeld, Postfach 100131, 33501 Bielefeld (Germany); Kutoviy, Oleksandr, E-mail: kutoviy@math.uni-bielefeld.de, E-mail: kutovyi@mit.edu [Fakultät für Mathematik, Universität Bielefeld, Postfach 100131, 33501 Bielefeld (Germany); Department of Mathematics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139 (United States); Minlos, Robert, E-mail: minl@iitp.ru; Pirogov, Sergey, E-mail: pirogov@proc.ru [IITP, RAS, Bolshoi Karetnyi 19, Moscow (Russian Federation)

    2013-11-15

    We discuss the selection procedure in the framework of mutation models. We study the regulation for stochastically developing systems based on a transformation of the initial Markov process which includes a cost functional. The transformation of initial Markov process by cost functional has an analytic realization in terms of a Kimura-Maruyama type equation for the time evolution of states or in terms of the corresponding Feynman-Kac formula on the path space. The state evolution of the system including the limiting behavior is studied for two types of mutation-selection models.

  14. Comparison of Models for Ball Bearing Dynamic Capacity and Life

    Science.gov (United States)

    Gupta, Pradeep K.; Oswald, Fred B.; Zaretsky, Erwin V.

    2015-01-01

    Generalized formulations for dynamic capacity and life of ball bearings, based on the models introduced by Lundberg and Palmgren and Zaretsky, have been developed and implemented in the bearing dynamics computer code, ADORE. Unlike the original Lundberg-Palmgren dynamic capacity equation, where the elastic properties are part of the life constant, the generalized formulations permit variation of elastic properties of the interacting materials. The newly updated Lundberg-Palmgren model allows prediction of life as a function of elastic properties. For elastic properties similar to those of AISI 52100 bearing steel, both the original and updated Lundberg-Palmgren models provide identical results. A comparison between the Lundberg-Palmgren and the Zaretsky models shows that at relatively light loads the Zaretsky model predicts a much higher life than the Lundberg-Palmgren model. As the load increases, the Zaretsky model provides a much faster drop off in life. This is because the Zaretsky model is much more sensitive to load than the Lundberg-Palmgren model. The generalized implementation where all model parameters can be varied provides an effective tool for future model validation and enhancement in bearing life prediction capabilities.

  15. Advanced Control of Active Bearings - Modelling, Design and Experiments

    DEFF Research Database (Denmark)

    Theisen, Lukas Roy Svane

    , the enhancement of damping, the extension of operating range and the minimisation of critical vibrations in machine elements are of fundamental importance. The main component to tackle the energy-loss-related problems is the bearing. The area of design of active bearings, while very promising, is still in its...... control design. One example is the controllable radial gas bearing, where the lubricant air is injected through controllable injectors to levitate the rotor on an air film. Feedback control of the injection can improve upon the poor damping to reduce the disturbance sensitivity and vibrations near...... the critical speeds. The feedback control law is preferably designed from a simple model, which captures the dominant dynamics of the machine in the frequency range of interest. This thesis offers two main original contributions in the field of active bearings. First, an experimental technique is proposed...

  16. Hibernating bears as a model for preventing disuse osteoporosis

    Science.gov (United States)

    Donahue, S.W.; McGee, M.E.; Harvey, K.B.; Vaughan, M.R.; Robbins, C.T.

    2006-01-01

    The hibernating bear is an excellent model for disuse osteoporosis in humans because it is a naturally occurring large animal model. Furthermore, bears and humans have similar lower limb skeletal morphology, and bears walk plantigrade like humans. Black bears (Ursus americanus) may not develop disuse osteoporosis during long periods of disuse (i.e. hibernation) because they maintain osteoblastic bone formation during hibernation. As a consequence, bone volume, mineral content, porosity, and strength are not adversely affected by annual periods of disuse. In fact, cortical bone bending strength has been shown to increase with age in hibernating black bears without a significant change in porosity. Other animals require remobilization periods 2-3 times longer than the immobilization period to recover the bone lost during disuse. Our findings support the hypothesis that black bears, which hibernate for as long as 5-7 months annually, have evolved biological mechanisms to mitigate the adverse effects of disuse on bone porosity and strength. ?? 2005 Elsevier Ltd. All rights reserved.

  17. Numerical Investigation of Turbulence Models for a Superlaminar Journal Bearing

    Directory of Open Access Journals (Sweden)

    Aoshuang Ding

    2018-01-01

    Full Text Available With rotating machineries working at high speeds, oil flow in bearings becomes superlaminar. Under superlaminar conditions, flow exhibits between laminar and fully developed turbulence. In this study, superlaminar oil flow in an oil-lubricated tilting-pad journal bearing is analyzed through computational fluid dynamics (CFD. A three-dimensional bearing model is established. CFD results from the laminar model and 14 turbulence models are compared with experimental findings. The laminar simulation results of pad-side pressure are inconsistent with the experimental data. Thus, the turbulence effects on superlaminar flow should be considered. The simulated temperature and pressure distributions from the classical fully developed turbulence models cannot correctly fit the experimental data. As such, turbulence models should be corrected for superlaminar flow. However, several corrections, such as transition correction, are unsuitable. Among all the flow models, the SST model with low-Re correction exhibits the best pressure distribution and turbulence viscosity ratio. Velocity profile analysis confirms that a buffer layer plays an important role in the superlaminar boundary layer. Classical fully developed turbulence models cannot accurately predict the buffer layer, but this problem can be resolved by initiating an appropriate low-Re correction. Therefore, the SST model with low-Re correction yields suitable results for superlaminar flows in bearings.

  18. Finite element modelling of the dynamics of groovy ball bearings

    Directory of Open Access Journals (Sweden)

    Ajala Olamide

    2018-01-01

    Full Text Available Geometry modified thrust bearings exposed to rolling and sliding contact are subjected to wear and localized frictional heating caused by relative slip between the two sliding surfaces. This leads to a rise in temperature, thermal stresses and changes in the elastic and plastic strength and physical properties of the material. The changes in the properties in turn alter the stress state, the displacement field, life and reliability of the bearing. Hence, a finite-element model is created to study the dynamics of groovy thrust bearing. In this paper, Hertz contact theory and numerical method are used to simulate the dynamics and kinematics of groovy ball bearings. The optimal loading parameters are identified in this study based on the analysis of the system responses and properties. The results of the numerical analysis and validation are presented. The numerical analysis proves the concept of transforming rotational motion into axial oscillation and demonstrates the capabilities of the numerical simulation to accurately model the dynamics of the groovy ball bearing.

  19. Seismic base isolation: Elastomer characterization, bearing modeling and system response

    International Nuclear Information System (INIS)

    Kulak, R.F.; Wang, C.Y.; Hughes, T.H.

    1991-01-01

    This paper discusses several major aspects of seismic base isolation systems that employ laminated elastomer bearings. Elastomer constitutive models currently being used to represent the nonlinear elastic and hysteretic behavior are discussed. Some aspects of mechanical characterization testing of elastomers is presented along with representative tests results. The development of a finite element based mesh generator for laminated elastomer bearings is presented. Recent advances in the simulation of base isolated structures to earthquake motions are presented along with a sample problem. 13 refs., 19 figs., 1 tab

  20. Seismic base isolation: Elastomer characterization, bearing modeling and system response

    Energy Technology Data Exchange (ETDEWEB)

    Kulak, R.F.; Wang, C.Y.; Hughes, T.H.

    1991-01-01

    This paper discusses several major aspects of seismic base isolation systems that employ laminated elastomer bearings. Elastomer constitutive models currently being used to represent the nonlinear elastic and hysteretic behavior are discussed. Some aspects of mechanical characterization testing of elastomers is presented along with representative tests results. The development of a finite element based mesh generator for laminated elastomer bearings is presented. Recent advances in the simulation of base isolated structures to earthquake motions are presented along with a sample problem. 13 refs., 19 figs., 1 tab.

  1. Exploring the common molecular basis for the universal DNA mutation bias: Revival of Loewdin mutation model

    International Nuclear Information System (INIS)

    Fu, Liang-Yu; Wang, Guang-Zhong; Ma, Bin-Guang; Zhang, Hong-Yu

    2011-01-01

    Highlights: → There exists a universal G:C → A:T mutation bias in three domains of life. → This universal mutation bias has not been sufficiently explained. → A DNA mutation model proposed by Loewdin 40 years ago offers a common explanation. -- Abstract: Recently, numerous genome analyses revealed the existence of a universal G:C → A:T mutation bias in bacteria, fungi, plants and animals. To explore the molecular basis for this mutation bias, we examined the three well-known DNA mutation models, i.e., oxidative damage model, UV-radiation damage model and CpG hypermutation model. It was revealed that these models cannot provide a sufficient explanation to the universal mutation bias. Therefore, we resorted to a DNA mutation model proposed by Loewdin 40 years ago, which was based on inter-base double proton transfers (DPT). Since DPT is a fundamental and spontaneous chemical process and occurs much more frequently within GC pairs than AT pairs, Loewdin model offers a common explanation for the observed universal mutation bias and thus has broad biological implications.

  2. Multicomponent gas mixture air bearing modeling via lattice Boltzmann method

    Science.gov (United States)

    Tae Kim, Woo; Kim, Dehee; Hari Vemuri, Sesha; Kang, Soo-Choon; Seung Chung, Pil; Jhon, Myung S.

    2011-04-01

    As the demand for ultrahigh recording density increases, development of an integrated head disk interface (HDI) modeling tool, which considers the air bearing and lubricant film morphology simultaneously is of paramount importance. To overcome the shortcomings of the existing models based on the modified Reynolds equation (MRE), the lattice Boltzmann method (LBM) is a natural choice in modeling high Knudsen number (Kn) flows owing to its advantages over conventional methods. The transient and parallel nature makes this LBM an attractive tool for the next generation air bearing design. Although LBM has been successfully applied to single component systems, a multicomponent system analysis has been thwarted because of the complexity in coupling the terms for each component. Previous studies have shown good results in modeling immiscible component mixtures by use of an interparticle potential. In this paper, we extend our LBM model to predict the flow rate of high Kn pressure-driven flows in multicomponent gas mixture air bearings, such as the air-helium system. For accurate modeling of slip conditions near the wall, we adopt our LBM scheme with spatially dependent relaxation times for air bearings in HDIs. To verify the accuracy of our code, we tested our scheme via simple two-dimensional benchmark flows. In the pressure-driven flow of an air-helium mixture, we found that the simple linear combination of pure helium and pure air flow rates, based on helium and air mole fraction, gives considerable error when compared to our LBM calculation. Hybridization with the existing MRE database can be adopted with the procedure reported here to develop the state-of-the-art slider design software.

  3. Experimental Investigation of Friction Effect on Liner Model Rolling Bearings for Large Diameter Thrust Bearing Design

    Directory of Open Access Journals (Sweden)

    S. Babu

    2012-12-01

    Full Text Available Studying friction coefficient has significant importance, especially when dealing with high load and temperature applications that have frequent starting and stopping points. Towards that, two sets of angular contact Linear Model Mockup Bearings (LMMB were designed and fabricated. This linear model assembly was made up of high precision, grounded raceways (AISI 4140 and commercially purchased balls (AISI 52100. The experimental studies were carried out by placing different number of balls between the raceways under different loads at dry lubricating condition. The static friction coefficients were measured using two different experiments: viz gravitation-based experiment and direct linear force measurement experiment. And Digital Image Correlation (DIC technique was used to find the stiffness of LMMB set.

  4. Experimental validation of a bearing wear model using the directional response of the rotor-bearing system

    Directory of Open Access Journals (Sweden)

    Tiago Henrique Machado

    Full Text Available ABSTRACT The present work gives continuity in the analysis of the wear influence on cylindrical hydrodynamic bearings by presenting an experimental validation of the wear model previously proposed by the authors. This validation is carried on using the frequency response of the rotor-bearings system in directional coordinates. For this purpose, a test rig was assembled in order to evaluate the behavior of the rotating system when supported by hydrodynamic bearings with different wear patterns. The experimental measurements are used to validate the wear model, comparing the anisotropy influence on the experimental and numerical responses. The simulated directional frequency responses showed a good agreement with the experimental ones, demonstrating the potential of the proposed wear model in satisfactorily represent its influence on the rotor-bearings system response in the frequency range where the numerical model was validated.

  5. Experimental validation of a bearing wear model using the directional response of the rotor-bearing system.

    Science.gov (United States)

    Machado, Tiago Henrique; Cavalca, Katia L

    2016-01-01

    The present work gives continuity in the analysis of the wear influence on cylindrical hydrodynamic bearings by presenting an experimental validation of the wear model previously proposed by the authors. This validation is carried on using the frequency response of the rotor-bearings system in directional coordinates. For this purpose, a test rig was assembled in order to evaluate the behavior of the rotating system when supported by hydrodynamic bearings with different wear patterns. The experimental measurements are used to validate the wear model, comparing the anisotropy influence on the experimental and numerical responses. The simulated directional frequency responses showed a good agreement with the experimental ones, demonstrating the potential of the proposed wear model in satisfactorily represent its influence on the rotor-bearings system response in the frequency range where the numerical model was validated.

  6. Symmetry breaking in a bull and bear financial market model

    International Nuclear Information System (INIS)

    Sushko, Iryna; Tramontana, Fabio; Westerhoff, Frank; Avrutin, Viktor

    2015-01-01

    We investigate bifurcation structures in the parameter space of a one-dimensional piecewise linear map with two discontinuity points. This map describes endogenous bull and bear market dynamics arising from a simple asset-pricing model. An important feature of our model is that some speculators only enter the market if the price is sufficiently distant to its fundamental value. Our analysis starts with the investigation of a particular case in which the map is symmetric with respect to the origin, associated with equal market entry thresholds in the bull and bear market. We then generalize our analysis by exploring how novel bifurcation structures may emerge when the map’s symmetry is broken.

  7. Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations.

    Science.gov (United States)

    Hofer, D; Paul, K; Fantur, K; Beck, M; Roubergue, A; Vellodi, A; Poorthuis, B J; Michelakakis, H; Plecko, B; Paschke, E

    2010-09-01

    GM1 gangliosidosis manifests with progressive psychomotor deterioration and dysostosis of infantile, juvenile, or adult onset, caused by alterations in the structural gene coding for lysosomal acid beta-galactosidase (GLB1). In addition, allelic variants of this gene can result in Morquio B disease (MBD), a phenotype with dysostosis multiplex and entire lack of neurologic involvement. More than 100 sequence alterations in the GLB1 gene have been identified so far, but only few could be proven to be predictive for one of the GM1 gangliosidosis subtypes or MBD. We performed genotype analyses in 16 GM1 gangliosidosis patients of all phenotypes and detected 28 different genetic lesions. Among these, p.I55FfsX16, p.W65X, p.F107L, p.H112P, p.C127Y, p.W161X, p.I181K, p.C230R, p.W273X, p.R299VfsX5, p.A301V, p.F357L, p.K359KfsX23, p.L389P, p.D448V, p.D448GfsX8, and the intronic mutation IVS6-8A>G have not been published so far. Due to their occurrence in homozygous patients, four mutations could be correlated to a distinct GM1 gangliosidosis phenotype. Furthermore, the missense mutations from heteroallelic patients and three artificial nonsense mutations were characterized by overexpression in COS-1 cells, and the subcellular localization of the mutant proteins in fibroblasts was assessed. The phenotype specificity of 10 alleles can be proposed on the basis of our results and previous data.

  8. KINEMATICS AND DYNAMICS MODELS OF CYLINDRICAL ROLLER BEARING OF RAILWAY TRANSPORT

    Directory of Open Access Journals (Sweden)

    A. V. Gaydamaka

    2014-05-01

    Full Text Available Purpose. Lack of kinematics models and imperfection of the known dynamics models of the roller bearings of railway rolling stock axle-boxes do not allow designing the optimal structure of bearing cages, providing the required service life and reliability of bearing units of wheel sets for cars and locomotives. The studies of kinematics and dynamics of roller bearings of axle boxes for cars and locomotives and modeling of their parts interaction to create the analytical method of bearing cages calculation are necessary. Methodology. This purpose has been achieved due to the modeling of kinematics of the ideal (without gaps and real (taking account the gaps, manufacturing and installation errors bearings, substantiation of the transfer mechanism of motion from the rollers to bearing cage, modeling the dynamics of rolling, research of interaction forces of the rollers with bearing cage. Findings. It is established that the kinematics of ideal bearing is determined by the contact deformations of the rollers and rings, when the kinematics of real bearing depends mainly on the side gaps in the windows of the bearing cage. On the basis of studies of the real bearing kinematics the dynamics models of the rollers and bearing cage interaction were constructed. The conducted studies of kinematics and dynamics of rolling bearings have changed our view of them as of the planetary mechanism, explained the reason of bearing cage loading, and confirmed the possibility of destruction during operation. Originality. It was first proposed a mechanism for motion transfer from the rollers to the bearing cage of roller bearings, consisting in that the side gap in the bearing cage window is reduced gradually multiple of the number of rollers of radial loading area according to the bearing cage motion. The models of roller bearing dynamics, which allow calculating the interaction forces of parts for all modes of operation, were improved. Practical value. Use of the

  9. A general model for preload calculation and stiffness analysis for combined angular contact ball bearings

    Science.gov (United States)

    Zhang, Jinhua; Fang, Bin; Hong, Jun; Wan, Shaoke; Zhu, Yongsheng

    2017-12-01

    The combined angular contact ball bearings are widely used in automatic, aerospace and machine tools, but few researches on the combined angular contact ball bearings have been reported. It is shown that the preload and stiffness of combined bearings are mutual influenced rather than simply the superposition of multiple single bearing, therefore the characteristic calculation of combined bearings achieved by coupling the load and deformation analysis of a single bearing. In this paper, based on the Jones quasi-static model and stiffness analytical model, a new iterative algorithm and model are proposed for the calculation of combined bearings preload and stiffness, and the dynamic effects include centrifugal force and gyroscopic moment have to be considered. It is demonstrated that the new method has general applicability, the preload factors of combined bearings are calculated according to the different design preloads, and the static and dynamic stiffness for various arrangements of combined bearings are comparatively studied and analyzed, and the influences of the design preload magnitude, axial load and rotating speed are discussed in detail. Besides, the change rule of dynamic contact angles of combined bearings with respect to the rotating speed is also discussed. The results show that bearing arrangement modes, rotating speed and design preload magnitude have a significant influence on the preload and stiffness of combined bearings. The proposed formulation provides a useful tool in dynamic analysis of the complex bearing-rotor system.

  10. High-Speed Shaft Bearing Loads Testing and Modeling in the NREL Gearbox Reliability Collaborative: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    McNiff, B.; Guo, Y.; Keller, J.; Sethuraman, L.

    2014-12-01

    Bearing failures in the high speed output stage of the gearbox are plaguing the wind turbine industry. Accordingly, the National Renewable Energy Laboratory (NREL) Gearbox Reliability Collaborative (GRC) has performed an experimental and theoretical investigation of loads within these bearings. The purpose of this paper is to describe the instrumentation, calibrations, data post-processing and initial results from this testing and modeling effort. Measured HSS torque, bending, and bearing loads are related to model predictions. Of additional interest is examining if the shaft measurements can be simply related to bearing load measurements, eliminating the need for invasive modifications of the bearing races for such instrumentation.

  11. On The Modeling Of Hybrid Aerostatic - Gas Journal Bearings

    DEFF Research Database (Denmark)

    Morosi, Stefano; Santos, Ilmar

    2010-01-01

    of a compressible fluid film journal bearing. Control forces are generated by injecting pressurized air into the bearing gap through orifices located on the bearing walls. A modified form of the compressible Reynolds equation for active lubrication is derived. By solving this equation, stiffness and damping......Gas journal bearing have been increasingly adopted in modern turbo-machinery applications, as they meet the demands of operation at higher rotational speeds, in clean environment and great efficiency. Due to the fact that gaseous lubricants, typically air, have much lower viscosity than more...

  12. Fitness effects of beneficial mutations: the mutational landscape model in experimental evolution

    DEFF Research Database (Denmark)

    Betancourt, Andrea J.; Bollback, Jonathan Paul

    2006-01-01

    of beneficial mutations should be roughly exponentially distributed. The prediction appears to be borne out by most of these studies, at least qualitatively. Another study showed that a modified version of the model was able to predict, with reasonable accuracy, which of a ranked set of beneficial alleles...... will be fixed next. Although it remains to be seen whether the mutational landscape model adequately describes adaptation in organisms other than microbes, together these studies suggest that adaptive evolution has surprisingly general properties that can be successfully captured by theoretical models....

  13. MODELLING OF THERMOELASTIC TRANSIENT CONTACT INTERACTION FOR BINARY BEARING TAKING INTO ACCOUNT CONVECTION

    Directory of Open Access Journals (Sweden)

    Igor KOLESNIKOV

    2016-12-01

    Full Text Available Serviceability of metal-polymeric "dry-friction" sliding bearings depends on many parameters, including the rotational speed, friction coefficient, thermal and mechanical properties of the bearing system and, as a result, the value of contact temperature. The objective of this study is to develop a computational model for the metallic-polymer bearing, determination on the basis of this model temperature distribution, equivalent and contact stresses for elements of the bearing arrangement and selection of the optimal parameters for the bearing system to achieve thermal balance. Static problem for the combined sliding bearing with the account of heat generation due to friction has been studied in [1]; the dynamic thermoelastic problem of the shaft rotation in a single and double layer bronze bearings were investigated in [2, 3].

  14. Hydrate-CASM for modeling Methane Hydrate-Bearing Sediments

    Science.gov (United States)

    De La Fuente Ruiz, M.; Vaunat, J.; Marin Moreno, H.

    2017-12-01

    A clear understanding of the geomechanical behavior of methane hydrate-bearing sediments (MHBS) is crucial to assess the stability of the seafloor and submarine infrastructures to human and natural loading changes. Here we present the Hydrate-CASM, a new elastoplastic constitutive model to predict the geomechanical behavior of MHBS. Our model employs the critical state model CASM (Clay and Sand Model) because of its flexibility in describing the shape of the yield surface and its proven ability to predict the mechanical behavior of sands, the most commercially viable hydrate reservoirs. The model considers MHBS as a deformable elastoplastic continuum, and hydrate-related changes in the stress-strain behavior are predicted by a densification mechanism. The densification attributes the mechanical contribution of hydrate to; a reduction of the available void ratio; a decrease of the swelling line slope; and an increase of the volumetric yield stress. It is described by experimentally derived physical parameters except from the swelling slope coefficient that requires empirical calibration. The Hydrate-CASM is validated against published triaxial laboratory tests performed at different confinement stresses, hydrate saturations, and hydrate morphologies. During the validation, we focused on capturing the mechanical behavior of the host sediment and consider perturbations of the sediment's mechanical properties that could result from the sample preparation. Our model successfully captures the experimentally observed influence of hydrate saturation in the magnitude and trend of the stiffness, shear strength, and dilatancy of MHBS. Hence, we propose that hydrate-related densification changes might be a major factor controlling the geomechanical response of MHBS.

  15. Modeling and Analysis of the Static Characteristics and Dynamic Responses of Herringbone-grooved Thrust Bearings

    Science.gov (United States)

    Yu, Yunluo; Pu, Guang; Jiang, Kyle

    2017-12-01

    This paper describes a theoretical investigation of static and dynamic characteristics of herringbone-grooved air thrust bearings. Firstly, Finite Difference Method (FDM) and Finite Volume Method (FVM) are used in combination to solve the non-linear Reynolds equation and to find the pressure distribution of the film and the total loading capacity of the bearing. The influence of design parameters on air film gap characteristics, including the air film thickness, depth of the groove and rotating speed, are analyzed based on the FDM model. The simulation results show that hydrostatic thrust bearings can achieve a better load capacity with less air consumption than herringbone grooved thrust bearings at low compressibility number; herringbone grooved thrust bearings can achieve a higher load capacity but with more air consumption than hydrostatic thrust bearing at high compressibility number; herringbone grooved thrust bearings would lose stability at high rotating speeds, and the stability increases with the depth of the grooves.

  16. Modeling survival: application of the Andersen-Gill model to Yellowstone grizzly bears

    Science.gov (United States)

    Johnson, Christopher J.; Boyce, Mark S.; Schwartz, Charles C.; Haroldson, Mark A.

    2004-01-01

     Wildlife ecologists often use the Kaplan-Meier procedure or Cox proportional hazards model to estimate survival rates, distributions, and magnitude of risk factors. The Andersen-Gill formulation (A-G) of the Cox proportional hazards model has seen limited application to mark-resight data but has a number of advantages, including the ability to accommodate left-censored data, time-varying covariates, multiple events, and discontinuous intervals of risks. We introduce the A-G model including structure of data, interpretation of results, and assessment of assumptions. We then apply the model to 22 years of radiotelemetry data for grizzly bears (Ursus arctos) of the Greater Yellowstone Grizzly Bear Recovery Zone in Montana, Idaho, and Wyoming, USA. We used Akaike's Information Criterion (AICc) and multi-model inference to assess a number of potentially useful predictive models relative to explanatory covariates for demography, human disturbance, and habitat. Using the most parsimonious models, we generated risk ratios, hypothetical survival curves, and a map of the spatial distribution of high-risk areas across the recovery zone. Our results were in agreement with past studies of mortality factors for Yellowstone grizzly bears. Holding other covariates constant, mortality was highest for bears that were subjected to repeated management actions and inhabited areas with high road densities outside Yellowstone National Park. Hazard models developed with covariates descriptive of foraging habitats were not the most parsimonious, but they suggested that high-elevation areas offered lower risks of mortality when compared to agricultural areas.

  17. Modelling and Identification for Control of Gas Bearings

    DEFF Research Database (Denmark)

    Theisen, Lukas Roy Svane; Niemann, Hans Henrik; Santos, Ilmar

    2015-01-01

    Gas bearings are popular for their high speed capabilities, low friction and clean operation, but suffer from poor damping, which poses challenges for safe operation in presence of disturbances. Enhanced damping can be achieved through active lubrication techniques using feedback control laws...... to industrial rotating machinery with gas bearings and to allow for subsequent control design. The paper shows how piezoelectric actuators in a gas bearing are efficiently used to perturb the gas film for identification over relevant ranges of rotational speed and gas injection pressure. Parameter...

  18. Improving Rolling Bearing Fault Diagnosis by DS Evidence Theory Based Fusion Model

    Directory of Open Access Journals (Sweden)

    Xuemei Yao

    2017-01-01

    Full Text Available Rolling bearing plays an important role in rotating machinery and its working condition directly affects the equipment efficiency. While dozens of methods have been proposed for real-time bearing fault diagnosis and monitoring, the fault classification accuracy of existing algorithms is still not satisfactory. This work presents a novel algorithm fusion model based on principal component analysis and Dempster-Shafer evidence theory for rolling bearing fault diagnosis. It combines the advantages of the learning vector quantization (LVQ neural network model and the decision tree model. Experiments under three different spinning bearing speeds and two different crack sizes show that our fusion model has better performance and higher accuracy than either of the base classification models for rolling bearing fault diagnosis, which is achieved via synergic prediction from both types of models.

  19. On the simplifications for the thermal modeling of tilting-pad journal bearings under thermoelastohydrodynamic regime

    DEFF Research Database (Denmark)

    Cerda Varela, Alejandro Javier; Fillon, Michel; Santos, Ilmar

    2012-01-01

    The relevance of calculating accurately the oil film temperature build up when modeling tilting-pad journal bearings is well established within the literature on the subject. This work studies the feasibility of using a thermal model for the tilting-pad journal bearing which includes a simplified...

  20. The bear in Eurasian plant names: motivations and models.

    Science.gov (United States)

    Kolosova, Valeria; Svanberg, Ingvar; Kalle, Raivo; Strecker, Lisa; Özkan, Ayşe Mine Gençler; Pieroni, Andrea; Cianfaglione, Kevin; Molnár, Zsolt; Papp, Nora; Łuczaj, Łukasz; Dimitrova, Dessislava; Šeškauskaitė, Daiva; Roper, Jonathan; Hajdari, Avni; Sõukand, Renata

    2017-02-21

    Ethnolinguistic studies are important for understanding an ethnic group's ideas on the world, expressed in its language. Comparing corresponding aspects of such knowledge might help clarify problems of origin for certain concepts and words, e.g. whether they form common heritage, have an independent origin, are borrowings, or calques. The current study was conducted on the material in Slavonic, Baltic, Germanic, Romance, Finno-Ugrian, Turkic and Albanian languages. The bear was chosen as being a large, dangerous animal, important in traditional culture, whose name is widely reflected in folk plant names. The phytonyms for comparison were mostly obtained from dictionaries and other publications, and supplemented with data from databases, the co-authors' field data, and archival sources (dialect and folklore materials). More than 1200 phytonym use records (combinations of a local name and a meaning) for 364 plant and fungal taxa were recorded to help find out the reasoning behind bear-nomination in various languages, as well as differences and similarities between the patterns among them. Among the most common taxa with bear-related phytonyms were Arctostaphylos uva-ursi (L.) Spreng., Heracleum sphondylium L., Acanthus mollis L., and Allium ursinum L., with Latin loan translation contributing a high proportion of the phytonyms. Some plants have many and various bear-related phytonyms, while others have only one or two bear names. Features like form and/or surface generated the richest pool of names, while such features as colour seemed to provoke rather few associations with bears. The unevenness of bear phytonyms in the chosen languages was not related to the size of the language nor the present occurence of the Brown Bear in the region. However, this may, at least to certain extent, be related to the amount of the historical ethnolinguistic research done on the selected languages.

  1. Exploring the common molecular basis for the universal DNA mutation bias: revival of Löwdin mutation model.

    Science.gov (United States)

    Fu, Liang-Yu; Wang, Guang-Zhong; Ma, Bin-Guang; Zhang, Hong-Yu

    2011-06-10

    Recently, numerous genome analyses revealed the existence of a universal G:C→A:T mutation bias in bacteria, fungi, plants and animals. To explore the molecular basis for this mutation bias, we examined the three well-known DNA mutation models, i.e., oxidative damage model, UV-radiation damage model and CpG hypermutation model. It was revealed that these models cannot provide a sufficient explanation to the universal mutation bias. Therefore, we resorted to a DNA mutation model proposed by Löwdin 40 years ago, which was based on inter-base double proton transfers (DPT). Since DPT is a fundamental and spontaneous chemical process and occurs much more frequently within GC pairs than AT pairs, Löwdin model offers a common explanation for the observed universal mutation bias and thus has broad biological implications. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Nonlinear Transient Modeling and Design of Turbocharger Rotor/Semi-Floating Bush Bearing System

    OpenAIRE

    Jianming Cao; Saeid Dousti; Paul Allaire; Tim Dimond

    2017-01-01

    This work presents the bearing design and analysis of radial semi-floating bush oil lubricated bearings for a typical industrial turbocharger configuration. Initially, the stability analysis for a linear rotor/bearing system is evaluated through eigenvalues and eigenvectors. The stiffness and damping coefficients of the inner oil film are obtained for the linear modeling process. The operating speed range of the turbocharger is high enough, at 21,000 to 24,000 rpm, to be unstable, indicating ...

  3. Myeloid malignancies: mutations, models and management

    International Nuclear Information System (INIS)

    Murati, Anne; Brecqueville, Mandy; Devillier, Raynier; Mozziconacci, Marie-Joelle; Gelsi-Boyer, Véronique; Birnbaum, Daniel

    2012-01-01

    Myeloid malignant diseases comprise chronic (including myelodysplastic syndromes, myeloproliferative neoplasms and chronic myelomonocytic leukemia) and acute (acute myeloid leukemia) stages. They are clonal diseases arising in hematopoietic stem or progenitor cells. Mutations responsible for these diseases occur in several genes whose encoded proteins belong principally to five classes: signaling pathways proteins (e.g. CBL, FLT3, JAK2, RAS), transcription factors (e.g. CEBPA, ETV6, RUNX1), epigenetic regulators (e.g. ASXL1, DNMT3A, EZH2, IDH1, IDH2, SUZ12, TET2, UTX), tumor suppressors (e.g. TP53), and components of the spliceosome (e.g. SF3B1, SRSF2). Large-scale sequencing efforts will soon lead to the establishment of a comprehensive repertoire of these mutations, allowing for a better definition and classification of myeloid malignancies, the identification of new prognostic markers and therapeutic targets, and the development of novel therapies. Given the importance of epigenetic deregulation in myeloid diseases, the use of drugs targeting epigenetic regulators appears as a most promising therapeutic approach

  4. Myeloid malignancies: mutations, models and management

    Directory of Open Access Journals (Sweden)

    Murati Anne

    2012-07-01

    Full Text Available Abstract Myeloid malignant diseases comprise chronic (including myelodysplastic syndromes, myeloproliferative neoplasms and chronic myelomonocytic leukemia and acute (acute myeloid leukemia stages. They are clonal diseases arising in hematopoietic stem or progenitor cells. Mutations responsible for these diseases occur in several genes whose encoded proteins belong principally to five classes: signaling pathways proteins (e.g. CBL, FLT3, JAK2, RAS, transcription factors (e.g. CEBPA, ETV6, RUNX1, epigenetic regulators (e.g. ASXL1, DNMT3A, EZH2, IDH1, IDH2, SUZ12, TET2, UTX, tumor suppressors (e.g. TP53, and components of the spliceosome (e.g. SF3B1, SRSF2. Large-scale sequencing efforts will soon lead to the establishment of a comprehensive repertoire of these mutations, allowing for a better definition and classification of myeloid malignancies, the identification of new prognostic markers and therapeutic targets, and the development of novel therapies. Given the importance of epigenetic deregulation in myeloid diseases, the use of drugs targeting epigenetic regulators appears as a most promising therapeutic approach.

  5. Spatial Fleming-Viot models with selection and mutation

    CERN Document Server

    Dawson, Donald A

    2014-01-01

    This book constructs a rigorous framework for analysing selected phenomena in evolutionary theory of populations arising due to the combined effects of migration, selection and mutation in a spatial stochastic population model, namely the evolution towards fitter and fitter types through punctuated equilibria. The discussion is based on a number of new methods, in particular multiple scale analysis, nonlinear Markov processes and their entrance laws, atomic measure-valued evolutions and new forms of duality (for state-dependent mutation and multitype selection) which are used to prove ergodic theorems in this context and are applicable for many other questions and renormalization analysis for a variety of phenomena (stasis, punctuated equilibrium, failure of naive branching approximations, biodiversity) which occur due to the combination of rare mutation, mutation, resampling, migration and selection and make it necessary to mathematically bridge the gap (in the limit) between time and space scales.

  6. Non-linear journal bearing model for analysis of superharmonic vibrations of rotor systems

    Energy Technology Data Exchange (ETDEWEB)

    Hannukainen, P.

    2008-07-01

    A rotating machine usually consists of a rotor and bearings that supports it. The nonidealities in these components may excite vibration of the rotating system. The uncontrolled vibrations may lead to excessive wearing of the components of the rotating machine or reduce the process quality. Vibrations may be harmful even when amplitudes are seemingly low, as is usually the case in superharmonic vibration that takes place below the first critical speed of the rotating machine. Superharmonic vibration is excited when the rotational velocity of the machine is a fraction of the natural frequency of the system. In such a situation, a part of the machineAEs rotational energy is transformed into vibration energy. The amount of vibration energy should be minimised in the design of rotating machines. The superharmonic vibration phenomena can be studied by analysing the coupled rotor-bearing system employing a multibody simulation approach. This research is focused on the modelling of hydrodynamic journal bearings and rotorbearing systems supported by journal bearings. In particular, the non-idealities affecting the rotor-bearing system and their effect on the superharmonic vibration of the rotating system are analysed. A comparison of computationally efficient journal bearing models is carried out in order to validate one model for further development. The selected bearing model is improved in order to take the waviness of the shaft journal into account. The improved model is implemented and analyzed in a multibody simulation code. A rotor-bearing system that consists of a flexible tube roll, two journal bearings and a supporting structure is analysed employing the multibody simulation technique. The modelled non-idealities are the shell thickness variation in the tube roll and the waviness of the shaft journal in the bearing assembly. Both modelled non-idealities may cause subharmonic resonance in the system. In multibody simulation, the coupled effect of the non

  7. Model-Based Control Design for Flexible Rotors Supported by Active Gas Bearings - Theory & Experiment

    DEFF Research Database (Denmark)

    Pierart Vásquez, Fabián Gonzalo

    work, the control signal design is based on a theoretical model. This approach enables easy modifications of any of the numerous physical parameters in the system if needed. The theoretical model used is based on a modifed version of Reynolds equation where an extra term is added in order to include...... the critical speeds. In order to overcome such limitations, a mechatronic device has been proposed as a possible solution. This device named "hybrid active radial gas bearing" or simply "active gas bearing", combines an aerodynamic gas journal bearing with piezoelectrically controlled injectors. In the present...... frequencies and damping ratios of the rotor-bearing system) is performed and finally to design controllers that allows improvement of the dynamic properties of the rotor-active gas bearings system and lets the systemto safely cross the critical speeds, using the theoretical model as a design tool. The results...

  8. Persistent Unresolved Inflammation in the Mecp2-308 Female Mutated Mouse Model of Rett Syndrome

    Directory of Open Access Journals (Sweden)

    Alessio Cortelazzo

    2017-01-01

    Full Text Available Rett syndrome (RTT is a rare neurodevelopmental disorder usually caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2. Several Mecp2 mutant mouse lines have been developed recapitulating part of the clinical features. In particular, Mecp2-308 female heterozygous mice, bearing a truncating mutation, are a validated model of the disease. While recent data suggest a role for inflammation in RTT, little information on the inflammatory status in murine models of the disease is available. Here, we investigated the inflammatory status by proteomic 2-DE/MALDI-ToF/ToF analyses in symptomatic Mecp2-308 female mice. Ten differentially expressed proteins were evidenced in the Mecp2-308 mutated plasma proteome. In particular, 5 positive acute-phase response (APR proteins increased (i.e., kininogen-1, alpha-fetoprotein, mannose-binding protein C, alpha-1-antitrypsin, and alpha-2-macroglobulin, and 3 negative APR reactants were decreased (i.e., serotransferrin, albumin, and apolipoprotein A1. CD5 antigen-like and vitamin D-binding protein, two proteins strictly related to inflammation, were also changed. These results indicate for the first time a persistent unresolved inflammation of unknown origin in the Mecp2-308 mouse model.

  9. Toward a 3D dynamic model of a faulty duplex ball bearing

    Science.gov (United States)

    Kogan, Gideon; Klein, Renata; Kushnirsky, Alex; Bortman, Jacob

    2015-03-01

    Bearings are vital components for safe and proper operation of machinery. Increasing efficiency of bearing diagnostics usually requires training of health and usage monitoring systems via expensive and time-consuming ground calibration tests. The main goal of this research, therefore, is to improve bearing dynamics modeling tools in order to reduce the time and budget needed to implement the health and usage monitoring approach. The proposed three-dimensional ball bearing dynamic model is based on the classic dynamic and kinematic equations. Interactions between the bodies are simulated using non-linear springs combined with dampers described by Hertz-type contact relation. The force friction is simulated using the hyperbolic-tangent function. The model allows simulation of a wide range of mechanical faults. It is validated by comparison to known bearing behavior and to experimental results. The model results are verified by demonstrating numerical convergence. The model results for the two cases of single and duplex angular ball bearings with axial deformation in the outer ring are presented. The qualitative investigation provides insight into bearing dynamics, the sensitivity study generalizes the qualitative findings for similar cases, and the comparison to the test results validates model reliability. The article demonstrates the variety of the cases that the 3D bearing model can simulate and the findings to which it may lead. The research allowed the identification of new patterns generated by single and duplex bearings with axially deformed outer race. It also enlightened the difference between single and duplex bearing manifestation. In the current research the dynamic model enabled better understanding of the physical behavior of the faulted bearings. Therefore, it is expected that the modeling approach has the potential to simplify and improve the development process of diagnostic algorithms. • A deformed outer race of a single axially loaded bearing is

  10. The first Korean case of Beare-Stevenson syndrome with a Tyr375Cys mutation in the fibroblast growth factor receptor 2 gene.

    Science.gov (United States)

    Eun, So-Hee; Ha, Ki Ssu; Je, Bo-Kyung; Lee, Eung Seok; Choi, Byung Min; Lee, Jung Hwa; Eun, Baik-Lin; Yoo, Kee Hwan

    2007-04-01

    Here we report the first case of a Korean infant with a cloverleaf-shaped craniosynostosis, in which the diagnosis of Beare-Stevenson syndrome was suspected upon observation of the typical morphological features. This infant exhibited craniofacial anomalies, ocular proptosis, cutis gyrata, acanthosis nigricans, prominent umbilical stump, furrowed palms and soles, hypospadia, and sacral skin tag coupled with dermal sinus tract. Brain magnetic resonance imaging revealed that the patient also had non-communicating hydrocephalus with Chiari malformation. This is the 8th report of Beare-Stevenson syndrome in the literature, which was confirmed by the detection of a Tyr375Cys mutation in the fibroblast growth factor receptor 2 (FGFR2) gene.

  11. Modelling of LEG tilting pad journal bearings with active lubrication

    DEFF Research Database (Denmark)

    Cerda Varela, Alejandro Javier; García, Asier Bengoechea; Santos, Ilmar

    2017-01-01

    This work constitutes the first step in a research effort aimed at studying the feasibility of introducing an active lubrication concept in tilting pad journal bearings (TPJBs) that feature the leading edge groove (LEG) lubrication system. The modification of the oil flow into each pad supply gro...

  12. Unified coordinate system model for performance calculation of fix-pad journal bearing with different pad preload

    Science.gov (United States)

    Zhu, Aibin; Yang, Yulei; Chen, Wei; Yuan, Xiaoyang

    2014-05-01

    Traditional model for calculating performance parameters of a fix-pad journal bearing leads to heavy workload, complicated and changeable formulae as it requires deriving various geometric formulae with different bearing types such as circular journal bearing, dislocated bearing and elliptic bearing. Considering different pad preload ratios for non-standard bearing, traditional model not only becomes more complicated but also reduces scalability and promotion of the calculation programs. For the complexly case of traditional model while dealing with various fix-pad journal bearings, unified coordinate system model for performance calculation of fix-pad journal bearing is presented in the paper. A unified coordinate system with the bearing center at the origin is established, and the eccentricity ratio and attitude angle of axis relative to each pad are calculated through the coordinates of journal center and each pad center. Geometric description of fix-pad journal bearing is unified in this model, which can be used for both various standard bearing and non-standard bearing with different pad preload ratios. Validity of this model is verified with an elliptical bearing. Performance of a non-standard four-leaf bearing with different pad preload ratios is calculated based on this model. The calculation result shows that increasing preload ratio of the pad 1 and keeping that of the left three pads constant improves bearing capacity, stiffness and damping coefficients. This research presents a unified coordinate system model unifies performance calculation of fix-pad journal bearings and studied a non-standard four-leaf bearing with different pad preload ratios, the research conclusions provides new methods for performance calculation of fix-pad journal bearings.

  13. Nonrandom duplication of the chromosome bearing a mutated Ha-ras-1 allele in mouse skin tumors

    International Nuclear Information System (INIS)

    Bianchi, A.B.; Aldaz, C.M.; Conti, C.J.

    1990-01-01

    The authors analyzed the normal/mutated allelic ratio of the Ha-ras-1 gene in mouse skin squamous cell carcinomas induced by initation with dimethylbenz[a]anthracene and promotion with phorbol 12-myristate 13-acetate. DNA for these studies was obtained from short-term tumor cultures (24-72 hr) to eliminate the contribution of stromal and inflammatory cells to the sample. The alelotypic analysis was performed in 25 squamous cell carcinomas by quantitative radio-analysis of the Xba I restriction fragment length polymorphism as detected by BS9, a v-Ha-ras probe, and rehybridization of the Southern blots with probes for chromosomes 7 and 9. Approximately 85% of the tumors presented overrepresentation of the mutated allele in the form of 1 normal/2 mutated (12 tumors), 0 normal/3 mutated (4 tumors), 0 normal/2 mutated (3 tumors), and gene amplification (3 tumors). No tumor was found with a 2 normal/1 mutated allelic ratio. These results support their previous cytogenetic studies, indicating that trisomy of chromosome 7 is present in themajority of these tumors show that nonrandom duplication of the chromosome carrying the mutated Ha-ras-1 allel appears to be a major mechanism by which the mutated gene is overrepresented

  14. Bearing Degradation Process Prediction Based on the Support Vector Machine and Markov Model

    Directory of Open Access Journals (Sweden)

    Shaojiang Dong

    2014-01-01

    Full Text Available Predicting the degradation process of bearings before they reach the failure threshold is extremely important in industry. This paper proposed a novel method based on the support vector machine (SVM and the Markov model to achieve this goal. Firstly, the features are extracted by time and time-frequency domain methods. However, the extracted original features are still with high dimensional and include superfluous information, and the nonlinear multifeatures fusion technique LTSA is used to merge the features and reduces the dimension. Then, based on the extracted features, the SVM model is used to predict the bearings degradation process, and the CAO method is used to determine the embedding dimension of the SVM model. After the bearing degradation process is predicted by SVM model, the Markov model is used to improve the prediction accuracy. The proposed method was validated by two bearing run-to-failure experiments, and the results proved the effectiveness of the methodology.

  15. Fractional model for heat conduction in polar bear hairs

    Directory of Open Access Journals (Sweden)

    Wang Qing-Li

    2012-01-01

    Full Text Available Time-fractional differential equations can accurately describe heat conduction in fractal media, such as wool fibers, goose down and polar bear hair. The fractional complex transform is used to convert time-fractional heat conduction equations with the modified Riemann-Liouville derivative into ordinary differential equations, and exact solutions can be easily obtained. The solution process is straightforward and concise.

  16. An Unsteady Long Bearing Squeeze Film Damper Model. Part 1; Circular Centered Orbits

    Science.gov (United States)

    Schallhorn, P. A.; Elrod, D. A.; Goggin, D. G.; Majumdar, A. K.

    2000-01-01

    This paper, the first of a two-part series, presents results of an unsteady rotordynamic analysis of a long-bearing squeeze film damper executing circular centered orbits using a fluid circuit approach. A series of nodes and branches represent the geometry of the flow circuit. The mass and momentum conservation equations are solved to predict the pressure distribution in the squeeze film. The motion of the bearing is simulated by the variation of geometry within the flow path. The modeling methodology is benchmarked against published experimental long-bearing squeeze film damper test results. The model provides good agreement with the experimental damping coefficient.

  17. Analysis of a Rough Elliptic Bore Journal Bearing using Expectancy Model of Roughness Characterization

    Directory of Open Access Journals (Sweden)

    P.C. Mishra

    2014-06-01

    Full Text Available Performance characteristics of a rough elliptic bore journal bearing are studied. The bearing bore of isotropic roughness orientation is characterized by stochastic function and the film geometry is quantified to elliptic shape. There after the Reynolds equation and energy equation are descretized for pressure and temperature respectively. A finite difference model is developed to evaluate hydrodynamic pressure and oil temperature. Solution to this model is done using effective influence Newton-Raphson method. Performance parameters such as load bearing ability, friction, flow-in and side leakages are computed and discussed.

  18. Rotor drop and following thermal growth simulations using detailed auxiliary bearing and damper models

    Science.gov (United States)

    Sun, Guangyoung

    2006-01-01

    Catcher bearings (CBs) or auxiliary bearings provide mechanical backup protection in the events of magnetic bearing failure. This paper presents numerical analysis for a rotor drop on CBs and following thermal growths due to their mechanical rub using detailed CB and damper models. The detailed CB model is determined based on its material, geometry, speed and preload using the nonlinear Hertzian load-deflection formula, and the thermal growths of bearing components during the rotor drop are estimated using a 1D thermal model. A finite-element squeeze film damper provides the pressure profile of an annular oil film and the resulting viscous damping force. Numerical simulations of an energy storage flywheel with magnetic suspensions failed reveal that an optimal CB design using the detailed simulation models stabilizes the rotor drop dynamics and lowers the thermal growths while preventing the high-speed backward whirl. Furthermore, CB design guides based on the simulation results are presented.

  19. Measurement of Pressure Fluctuations inside a Model Thrust Bearing Using PVDF Sensors.

    Science.gov (United States)

    Youssef, Andrew; Matthews, David; Guzzomi, Andrew; Pan, Jie

    2017-04-16

    Thrust bearings play a vital role in propulsion systems. They rely on a thin layer of oil being trapped between rotating surfaces to produce a low friction interface. The "quality" of this bearing affects many things from noise transmission to the ultimate catastrophic failure of the bearing itself. As a result, the direct measure of the forces and vibrations within the oil filled interface would be very desirable and would give an indication of the condition of the bearing in situ. The thickness of the oil film is, however, very small and conventional vibration sensors are too cumbersome to use in this confined space. This paper solves this problem by using a piezoelectric polymer film made from Polyvinylidine Fluoride (PVDF). These films are very thin (50 m) and flexible and easy to install in awkward spaces such as the inside of a thrust bearing. A model thrust bearing was constructed using a 3D printer and PVDF films inserted into the base of the bearing. In doing so, it was possible to directly measure the force fluctuations due to the rotating pads and investigate various properties of the thrust bearing itself.

  20. Finding all BRCA pathogenic mutation carriers: best practice models

    Science.gov (United States)

    Hoogerbrugge, Nicoline; Jongmans, Marjolijn CJ

    2016-01-01

    Identifying germline BRCA pathogenic mutations in patients with ovarian or breast cancer is a crucial component in the medical management of affected patients. Furthermore, the relatives of affected patients can be offered genetic testing. Relatives who test positive for a germline BRCA pathogenic mutation can take appropriate action to prevent cancer or have cancer diagnosed as early as possible for better treatment options. The recent discovery that BRCA pathogenic mutation status can inform treatment decisions in patients with ovarian cancer has led to an increased demand for BRCA testing, with testing taking place earlier in the patient care pathway. New approaches to genetic counselling may be required to meet this greater demand for BRCA testing. This review discusses the need for best practices for genetic counselling and BRCA testing; it examines the challenges facing current practice and looks at adapted models of genetic counselling. PMID:27514840

  1. Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations

    Science.gov (United States)

    Gammage, Payam A; Rorbach, Joanna; Vincent, Anna I; Rebar, Edward J; Minczuk, Michal

    2014-01-01

    We designed and engineered mitochondrially targeted obligate heterodimeric zinc finger nucleases (mtZFNs) for site-specific elimination of pathogenic human mitochondrial DNA (mtDNA). We used mtZFNs to target and cleave mtDNA harbouring the m.8993T>G point mutation associated with neuropathy, ataxia, retinitis pigmentosa (NARP) and the “common deletion” (CD), a 4977-bp repeat-flanked deletion associated with adult-onset chronic progressive external ophthalmoplegia and, less frequently, Kearns-Sayre and Pearson's marrow pancreas syndromes. Expression of mtZFNs led to a reduction in mutant mtDNA haplotype load, and subsequent repopulation of wild-type mtDNA restored mitochondrial respiratory function in a CD cybrid cell model. This study constitutes proof-of-principle that, through heteroplasmy manipulation, delivery of site-specific nuclease activity to mitochondria can alleviate a severe biochemical phenotype in primary mitochondrial disease arising from deleted mtDNA species. PMID:24567072

  2. Effect of misreported family history on Mendelian mutation prediction models.

    Science.gov (United States)

    Katki, Hormuzd A

    2006-06-01

    People with familial history of disease often consult with genetic counselors about their chance of carrying mutations that increase disease risk. To aid them, genetic counselors use Mendelian models that predict whether the person carries deleterious mutations based on their reported family history. Such models rely on accurate reporting of each member's diagnosis and age of diagnosis, but this information may be inaccurate. Commonly encountered errors in family history can significantly distort predictions, and thus can alter the clinical management of people undergoing counseling, screening, or genetic testing. We derive general results about the distortion in the carrier probability estimate caused by misreported diagnoses in relatives. We show that the Bayes factor that channels all family history information has a convenient and intuitive interpretation. We focus on the ratio of the carrier odds given correct diagnosis versus given misreported diagnosis to measure the impact of errors. We derive the general form of this ratio and approximate it in realistic cases. Misreported age of diagnosis usually causes less distortion than misreported diagnosis. This is the first systematic quantitative assessment of the effect of misreported family history on mutation prediction. We apply the results to the BRCAPRO model, which predicts the risk of carrying a mutation in the breast and ovarian cancer genes BRCA1 and BRCA2.

  3. An exactly solvable, spatial model of mutation accumulation in cancer

    Science.gov (United States)

    Paterson, Chay; Nowak, Martin A.; Waclaw, Bartlomiej

    2016-12-01

    One of the hallmarks of cancer is the accumulation of driver mutations which increase the net reproductive rate of cancer cells and allow them to spread. This process has been studied in mathematical models of well mixed populations, and in computer simulations of three-dimensional spatial models. But the computational complexity of these more realistic, spatial models makes it difficult to simulate realistically large and clinically detectable solid tumours. Here we describe an exactly solvable mathematical model of a tumour featuring replication, mutation and local migration of cancer cells. The model predicts a quasi-exponential growth of large tumours, even if different fragments of the tumour grow sub-exponentially due to nutrient and space limitations. The model reproduces clinically observed tumour growth times using biologically plausible rates for cell birth, death, and migration rates. We also show that the expected number of accumulated driver mutations increases exponentially in time if the average fitness gain per driver is constant, and that it reaches a plateau if the gains decrease over time. We discuss the realism of the underlying assumptions and possible extensions of the model.

  4. Ball bearing defect models: A study of simulated and experimental fault signatures

    Science.gov (United States)

    Mishra, C.; Samantaray, A. K.; Chakraborty, G.

    2017-07-01

    Numerical model based virtual prototype of a system can serve as a tool to generate huge amount of data which replace the dependence on expensive and often difficult to conduct experiments. However, the model must be accurate enough to substitute the experiments. The abstraction level and details considered during model development depend on the purpose for which simulated data should be generated. This article concerns development of simulation models for deep groove ball bearings which are used in a variety of rotating machinery. The purpose of the model is to generate vibration signatures which usually contain features of bearing defects. Three different models with increasing level-of-complexity are considered: a bearing kinematics based planar motion block diagram model developed in MATLAB Simulink which does not explicitly consider cage and traction dynamics, a planar motion model with cage, traction and contact dynamics developed using multi-energy domain bond graph formalism in SYMBOLS software, and a detailed spatial multi-body dynamics model with complex contact and traction mechanics developed using ADAMS software. Experiments are conducted using Spectra Quest machine fault simulator with different prefabricated faulted bearings. The frequency domain characteristics of simulated and experimental vibration signals for different bearing faults are compared and conclusions are drawn regarding usefulness of the developed models.

  5. Hydrodynamic and hydrostatic modelling of hydraulic journal bearings considering small displacement condition

    Science.gov (United States)

    Chen, Chi-Yin; Chuang, Jen-Chen; Tu, Jia-Ying

    2016-09-01

    This paper proposes modified coefficients for the dynamic model of hydraulic journal bearing system that integrates the hydrodynamic and hydrostatic properties. In recent years, design of hydraulic bearing for machine tool attracts worldwide attention, because hydraulic bearings are able to provide higher capacity and accuracy with lower friction, compared to conventional bearing systems. In order to achieve active control of the flow pressure and enhance the operation accuracy, the dynamic model of hydraulic bearings need to be developed. Modified coefficients of hydrostatic stiffness, hydrodynamic stiffness, and squeeze damping of the dynamic model are presented in this work, which are derived referring to small displacement analysis from literature. The proposed modified coefficients and model, which consider the pressure variations, relevant geometry size, and fluid properties of the journal bearings, are able to characterise the hydrodynamic and hydrostatic properties with better precision, thus offering the following pragmatic contribution: (1) on-line prediction of the eccentricity and the position of the shaft in the face of external force that results in vibration; (2) development of active control system to regulate the supply flow pressure and to minimize the eccentricity of the shaft. Theoretical derivation and simulation results with different vibration cases are discussed to verify the proposed techniques.

  6. Nonlinear Transient Modeling and Design of Turbocharger Rotor/Semi-Floating Bush Bearing System

    Directory of Open Access Journals (Sweden)

    Jianming Cao

    2017-06-01

    Full Text Available This work presents the bearing design and analysis of radial semi-floating bush oil lubricated bearings for a typical industrial turbocharger configuration. Initially, the stability analysis for a linear rotor/bearing system is evaluated through eigenvalues and eigenvectors. The stiffness and damping coefficients of the inner oil film are obtained for the linear modeling process. The operating speed range of the turbocharger is high enough, at 21,000 to 24,000 rpm, to be unstable, indicating that the analysis should be and is carried out with nonlinear transient modeling. The nonlinear transient analysis evaluates the rotor and bush limit cycle orbits, rotor dynamics, the forces acting on the rotor and semi-floating bush surfaces, the oil flow through the bearing, the oil temperatures, and the power loss of the two oil films. The optimum design of a set of semi-floating bush bearings for this application depends strongly upon the clearances of the bush and squeeze film damper, usually expressed as the non-dimensional clearance to radius ratio. A typical clearance is evaluated to determine the bearing performance in terms of orbit size, forces acting on the bush and squeeze damper surfaces, oil flow through the bearing, power loss, and thermal heating. The nonlinear transient orbit values are evaluated for frequency content using the FFT to determine which orbits show both the synchronous and sub-synchronous vibration components and the associated rotor modes excited. These results are compared to the linear analysis over the operating speed range. The oil flow through the bearing component is much larger than the squeeze film damper. The forces acting on the bush and squeeze damper surfaces are related to the fatigue life of the bearing.

  7. Establishment of Approximate Analytical Model of Oil Film Force for Finite Length Tilting Pad Journal Bearings

    Directory of Open Access Journals (Sweden)

    Yongliang Wang

    2015-01-01

    Full Text Available Tilting pad bearings offer unique dynamic stability enabling successful deployment of high-speed rotating machinery. The model of dynamic stiffness, damping, and added mass coefficients is often used for rotordynamic analyses, and this method does not suffice to describe the dynamic behaviour due to the nonlinear effects of oil film force under larger shaft vibration or vertical rotor conditions. The objective of this paper is to present a nonlinear oil force model for finite length tilting pad journal bearings. An approximate analytic oil film force model was established by analysing the dynamic characteristic of oil film of a single pad journal bearing using variable separation method under the dynamic π oil film boundary condition. And an oil film force model of a four-tilting-pad journal bearing was established by using the pad assembly technique and considering pad tilting angle. The validity of the model established was proved by analyzing the distribution of oil film pressure and the locus of journal centre for tilting pad journal bearings and by comparing the model established in this paper with the model established using finite difference method.

  8. Dynamic Model and Fault Feature Research of Dual-Rotor System with Bearing Pedestal Looseness

    Directory of Open Access Journals (Sweden)

    Nanfei Wang

    2016-01-01

    Full Text Available The paper presents a finite element model of dual-rotor system with pedestal looseness stemming from loosened bolts. Dynamic model including bearing pedestal looseness is established based on the dual-rotor test rig. Three-degree-of-freedom (DOF planar rigid motion of loose bearing pedestal is fully considered and collision recovery coefficient is also introduced in the model. Based on the Timoshenko beam elements, using the finite element method, rigid body kinematics, and the Newmark-β algorithm for numerical simulation, dynamic characteristics of the inner and outer rotors and the bearing pedestal plane rigid body motion under bearing pedestal looseness condition are studied. Meanwhile, the looseness experiments under two different speed combinations are carried out, and the experimental results are basically the same. The simulation results are compared with the experimental results, indicating that vibration displacement waveforms of loosened rotor have “clipping” phenomenon. When the bearing pedestal looseness fault occurs, the inner and outer rotors vibration spectrum not only contains the difference and sum frequency of the two rotors’ fundamental frequency but also contains 2X and 3X component of rotor with loosened support, and so forth; low frequency spectrum is more, containing dividing component, and so forth; the rotor displacement spectrums also contain fewer combination frequency components, and so forth; when one side of the inner rotor bearing pedestal is loosened, the inner rotor axis trajectory is drawn into similar-ellipse shape.

  9. Degradation Assessment and Fault Diagnosis for Roller Bearing Based on AR Model and Fuzzy Cluster Analysis

    Directory of Open Access Journals (Sweden)

    Lingli Jiang

    2011-01-01

    Full Text Available This paper proposes a new approach combining autoregressive (AR model and fuzzy cluster analysis for bearing fault diagnosis and degradation assessment. AR model is an effective approach to extract the fault feature, and is generally applied to stationary signals. However, the fault vibration signals of a roller bearing are non-stationary and non-Gaussian. Aiming at this problem, the set of parameters of the AR model is estimated based on higher-order cumulants. Consequently, the AR parameters are taken as the feature vectors, and fuzzy cluster analysis is applied to perform classification and pattern recognition. Experiments analysis results show that the proposed method can be used to identify various types and severities of fault bearings. This study is significant for non-stationary and non-Gaussian signal analysis, fault diagnosis and degradation assessment.

  10. A fully coupled air foil bearing model considering friction – Theory & experiment

    DEFF Research Database (Denmark)

    von Osmanski, Alexander Sebastian; Larsen, Jon Steffen; Santos, Ilmar

    2017-01-01

    The dynamics of air foil bearings (AFBs) are not yet fully captured by any model. The recent years have, however, seen promising results from nonlinear time domain models, and simultaneously coupled formulations are now available, avoiding the previous requirements for undesirably small time steps...

  11. Predicting 21st-century polar bear habitat distribution from global climate models

    Science.gov (United States)

    Durner, G.M.; Douglas, D.C.; Nielson, R.M.; Amstrup, Steven C.; McDonald, T.L.; Stirling, I.; Mauritzen, Mette; Born, E.W.; Wiig, O.; Deweaver, E.; Serreze, Mark C.; Belikov, Stanislav; Holland, M.M.; Maslanik, J.; Aars, Jon; Bailey, D.A.; Derocher, A.E.

    2009-01-01

    Projections of polar bear (Ursus maritimus) sea ice habitat distribution in the polar basin during the 21st century were developed to understand the consequences of anticipated sea ice reductions on polar bear populations. We used location data from satellitecollared polar bears and environmental data (e.g., bathymetry, distance to coastlines, and sea ice) collected from 1985 to 1995 to build resource selection functions (RSFs). RSFs described habitats that polar bears preferred in summer, autumn, winter, and spring. When applied to independent data from 1996 to 2006, the RSFs consistently identified habitats most frequently used by polar bears. We applied the RSFs to monthly maps of 21st-century sea ice concentration projected by 10 general circulation models (GCMs) used in the Intergovernmental Panel of Climate Change Fourth Assessment Report, under the A1B greenhouse gas forcing scenario. Despite variation in their projections, all GCMs indicated habitat losses in the polar basin during the 21st century. Losses in the highest-valued RSF habitat (optimal habitat) were greatest in the southern seas of the polar basin, especially the Chukchi and Barents seas, and least along the Arctic Ocean shores of Banks Island to northern Greenland. Mean loss of optimal polar bear habitat was greatest during summer; from an observed 1.0 million km2 in 1985-1995 (baseline) to a projected multi-model mean of 0.32 million km2 in 2090-2099 (-68% change). Projected winter losses of polar bear habitat were less: from 1.7 million km2 in 1985-1995 to 1.4 million km2 in 2090-2099 (-17% change). Habitat losses based on GCM multi-model means may be conservative; simulated rates of habitat loss during 1985-2006 from many GCMs were less than the actual observed rates of loss. Although a reduction in the total amount of optimal habitat will likely reduce polar bear populations, exact relationships between habitat losses and population demographics remain unknown. Density and energetic

  12. Predictive modeling and mapping of Malayan Sun Bear (Helarctos malayanus distribution using maximum entropy.

    Directory of Open Access Journals (Sweden)

    Mona Nazeri

    Full Text Available One of the available tools for mapping the geographical distribution and potential suitable habitats is species distribution models. These techniques are very helpful for finding poorly known distributions of species in poorly sampled areas, such as the tropics. Maximum Entropy (MaxEnt is a recently developed modeling method that can be successfully calibrated using a relatively small number of records. In this research, the MaxEnt model was applied to describe the distribution and identify the key factors shaping the potential distribution of the vulnerable Malayan Sun Bear (Helarctos malayanus in one of the main remaining habitats in Peninsular Malaysia. MaxEnt results showed that even though Malaysian sun bear habitat is tied with tropical evergreen forests, it lives in a marginal threshold of bio-climatic variables. On the other hand, current protected area networks within Peninsular Malaysia do not cover most of the sun bears potential suitable habitats. Assuming that the predicted suitability map covers sun bears actual distribution, future climate change, forest degradation and illegal hunting could potentially severely affect the sun bear's population.

  13. Predictive modeling and mapping of Malayan Sun Bear (Helarctos malayanus) distribution using maximum entropy.

    Science.gov (United States)

    Nazeri, Mona; Jusoff, Kamaruzaman; Madani, Nima; Mahmud, Ahmad Rodzi; Bahman, Abdul Rani; Kumar, Lalit

    2012-01-01

    One of the available tools for mapping the geographical distribution and potential suitable habitats is species distribution models. These techniques are very helpful for finding poorly known distributions of species in poorly sampled areas, such as the tropics. Maximum Entropy (MaxEnt) is a recently developed modeling method that can be successfully calibrated using a relatively small number of records. In this research, the MaxEnt model was applied to describe the distribution and identify the key factors shaping the potential distribution of the vulnerable Malayan Sun Bear (Helarctos malayanus) in one of the main remaining habitats in Peninsular Malaysia. MaxEnt results showed that even though Malaysian sun bear habitat is tied with tropical evergreen forests, it lives in a marginal threshold of bio-climatic variables. On the other hand, current protected area networks within Peninsular Malaysia do not cover most of the sun bears potential suitable habitats. Assuming that the predicted suitability map covers sun bears actual distribution, future climate change, forest degradation and illegal hunting could potentially severely affect the sun bear's population.

  14. Active lubrication applied to radial gas journal bearings. Part 2: Modelling improvement and experimental validation

    DEFF Research Database (Denmark)

    Pierart, Fabián G.; Santos, Ilmar F.

    2016-01-01

    Actively-controlled lubrication techniques are applied to radial gas bearings aiming at enhancing one of their most critical drawbacks, their lack of damping. A model-based control design approach is presented using simple feedback control laws, i.e. proportional controllers. The design approach...... by finite element method and the global model is used as control design tool. Active lubrication allows for significant increase in damping factor of the rotor-bearing system. Very good agreement between theory and experiment is obtained, supporting the multi-physic design tool developed....

  15. Mechanical model development of rolling bearing-rotor systems: A review

    Science.gov (United States)

    Cao, Hongrui; Niu, Linkai; Xi, Songtao; Chen, Xuefeng

    2018-03-01

    The rolling bearing rotor (RBR) system is the kernel of many rotating machines, which affects the performance of the whole machine. Over the past decades, extensive research work has been carried out to investigate the dynamic behavior of RBR systems. However, to the best of the authors' knowledge, no comprehensive review on RBR modelling has been reported yet. To address this gap in the literature, this paper reviews and critically discusses the current progress of mechanical model development of RBR systems, and identifies future trends for research. Firstly, five kinds of rolling bearing models, i.e., the lumped-parameter model, the quasi-static model, the quasi-dynamic model, the dynamic model, and the finite element (FE) model are summarized. Then, the coupled modelling between bearing models and various rotor models including De Laval/Jeffcott rotor, rigid rotor, transfer matrix method (TMM) models and FE models are presented. Finally, the paper discusses the key challenges of previous works and provides new insights into understanding of RBR systems for their advanced future engineering applications.

  16. Nondimensional characterization and asymptotic model development for multifunctional structures with application to load-bearing antennas

    International Nuclear Information System (INIS)

    Santapuri, Sushma; Bechtel, Stephen E

    2014-01-01

    This paper (i) presents a mathematical approach to formulate leading-order models for complex multifunctional systems with coupled thermomechanical and electromagnetic field interactions, and (ii) demonstrates its applicability to the modeling and analysis of a load-bearing antenna, a multifunctional sensing and transmitting device integrated with a load-bearing structure. Starting from first-principle equations, i.e. the thermomechanical balance laws coupled with Maxwell’s equations, nondimensionalization and perturbation techniques are employed to formulate a leading-order model for the coupled system. Depending on the design of the structure and nature of the excitation, the nondimensional numbers arising in the coupled multifunctional system are quantified, and through a relative ordering of these quantities, the dominant physical effects are extracted. The resulting dominant effects determine the regime of operation of the structure, and in turn dictate the appropriate computational model. This approach is demonstrated through an application to a load-bearing antenna for a prototypical design. The resulting leading-order model is subsequently solved, and the electrical and structural response of the load-bearing antenna is analyzed and compared for different combinations of material properties. The framework introduced in this paper is envisioned to have applications in developing leading-order models for a wide range of complex multifunctional systems and can be utilized for their efficient design. (paper)

  17. Study on p-Wave Attenuation in Hydrate-Bearing Sediments Based on BISQ Model

    Directory of Open Access Journals (Sweden)

    Chuanhui Li

    2013-01-01

    Full Text Available In hydrate-bearing sediments, the elastic wave attenuation characteristics depend on the elastic properties of the sediments themselves on the one hand, and on the other hand, they also depend on the hydrate occurrence state and hydrate saturation. Since the hydrate-bearing sediments always have high porosity, so they show significant porous medium characteristics. Based on the BISQ porous medium model which is the most widely used model to study the attenuation characteristics in the porous media, we focused on p-wave attenuation in hydrate-bearing sediments in Shenhu Area, South China Sea, especially in specific seismic frequency range, which lays a foundation for the identification of gas hydrates by using seismic wave attenuation in Shenhu Area, South China Sea. Our results depict that seismic wave attenuation is an effective attribute to identify gas hydrates.

  18. Fatigue behaviour FEM modeling of deep groove ball bearing mounted in automotive alternator submitted to variable loading

    Directory of Open Access Journals (Sweden)

    Azianou Ayao. E.

    2014-06-01

    Full Text Available Ball bearings subsurface materials are subjected to rolling contact fatigue with multiaxial stress state during loading cycle. The complex operating conditions of automotive bearings are different from classic operating conditions their fatigue crack initiation predicted by standards can be seen underestimated. This work presents a numerical approach of ball bearings to evaluate its fatigue behaviour in order to predict the life. A preliminary study has been done to evaluate the load distribution in the bearings. The results are integrated in a numerical dynamic model to study the bearing material rolling fatigue behaviour in constant and variable loading cases. By using fatigue criteria and damage laws, the analysis of stress state in bearing material leads to life prediction or the number of cycles before crack initiations. These results are compared to current standard methods used for ball bearing life prediction.

  19. Thin layer flow and film decay modeling for grease lubricated rolling bearings

    NARCIS (Netherlands)

    Venner, Cornelis H.; van Zoelen, M.T.; Lugt, Pieter Martin

    2012-01-01

    A model is presented to predict lubricant supply layer changes on tracks in rolling bearings due to centrifugal forces and elastohydrodynamic contact pressure. Experimental validation is shown for centrifugal force driven free surface flow, and layer thickness (film thickness) decay in single

  20. An Unsteady Long Bearing Squeeze Film Damper Model. Part 2; Statically Eccentric Operation

    Science.gov (United States)

    Schallhorn, P. A.; Elrod, D. A.; Goggin, D. G.; Majumdar, A. K.

    2000-01-01

    This paper, the second of a two-part series, presents results of an unsteady rotordynamic analysis of a long-bearing squeeze film damper executing orbits about an off center position using a fluid circuit approach. A series of nodes and branches represent the geometry of the flow circuit. The mass and momentum conservation equations are solved to predict the pressure distribution in the squeeze film. The motion of the bearing is simulated by the variation of geometry within the flow path. This effort represents the first modeling approach which allows for an arbitrary orbit size about an arbitrary position.

  1. A Hybrid Feature Model and Deep-Learning-Based Bearing Fault Diagnosis

    Directory of Open Access Journals (Sweden)

    Muhammad Sohaib

    2017-12-01

    Full Text Available Bearing fault diagnosis is imperative for the maintenance, reliability, and durability of rotary machines. It can reduce economical losses by eliminating unexpected downtime in industry due to failure of rotary machines. Though widely investigated in the past couple of decades, continued advancement is still desirable to improve upon existing fault diagnosis techniques. Vibration acceleration signals collected from machine bearings exhibit nonstationary behavior due to variable working conditions and multiple fault severities. In the current work, a two-layered bearing fault diagnosis scheme is proposed for the identification of fault pattern and crack size for a given fault type. A hybrid feature pool is used in combination with sparse stacked autoencoder (SAE-based deep neural networks (DNNs to perform effective diagnosis of bearing faults of multiple severities. The hybrid feature pool can extract more discriminating information from the raw vibration signals, to overcome the nonstationary behavior of the signals caused by multiple crack sizes. More discriminating information helps the subsequent classifier to effectively classify data into the respective classes. The results indicate that the proposed scheme provides satisfactory performance in diagnosing bearing defects of multiple severities. Moreover, the results also demonstrate that the proposed model outperforms other state-of-the-art algorithms, i.e., support vector machines (SVMs and backpropagation neural networks (BPNNs.

  2. A Hybrid Feature Model and Deep-Learning-Based Bearing Fault Diagnosis.

    Science.gov (United States)

    Sohaib, Muhammad; Kim, Cheol-Hong; Kim, Jong-Myon

    2017-12-11

    Bearing fault diagnosis is imperative for the maintenance, reliability, and durability of rotary machines. It can reduce economical losses by eliminating unexpected downtime in industry due to failure of rotary machines. Though widely investigated in the past couple of decades, continued advancement is still desirable to improve upon existing fault diagnosis techniques. Vibration acceleration signals collected from machine bearings exhibit nonstationary behavior due to variable working conditions and multiple fault severities. In the current work, a two-layered bearing fault diagnosis scheme is proposed for the identification of fault pattern and crack size for a given fault type. A hybrid feature pool is used in combination with sparse stacked autoencoder (SAE)-based deep neural networks (DNNs) to perform effective diagnosis of bearing faults of multiple severities. The hybrid feature pool can extract more discriminating information from the raw vibration signals, to overcome the nonstationary behavior of the signals caused by multiple crack sizes. More discriminating information helps the subsequent classifier to effectively classify data into the respective classes. The results indicate that the proposed scheme provides satisfactory performance in diagnosing bearing defects of multiple severities. Moreover, the results also demonstrate that the proposed model outperforms other state-of-the-art algorithms, i.e., support vector machines (SVMs) and backpropagation neural networks (BPNNs).

  3. Analytic Modeling of the Hydrodynamic, Thermal, and Structural Behavior of Foil Thrust Bearings

    Science.gov (United States)

    Bruckner, Robert J.; DellaCorte, Christopher; Prahl, Joseph M.

    2005-01-01

    A simulation and modeling effort is conducted on gas foil thrust bearings. A foil bearing is a self acting hydrodynamic device capable of separating stationary and rotating components of rotating machinery by a film of air or other gaseous lubricant. Although simple in appearance these bearings have proven to be complicated devices in analysis. They are sensitive to fluid structure interaction, use a compressible gas as a lubricant, may not be in the fully continuum range of fluid mechanics, and operate in the range where viscous heat generation is significant. These factors provide a challenge to the simulation and modeling task. The Reynolds equation with the addition of Knudsen number effects due to thin film thicknesses is used to simulate the hydrodynamics. The energy equation is manipulated to simulate the temperature field of the lubricant film and combined with the ideal gas relationship, provides density field input to the Reynolds equation. Heat transfer between the lubricant and the surroundings is also modeled. The structural deformations of the bearing are modeled with a single partial differential equation. The equation models the top foil as a thin, bending dominated membrane whose deflections are governed by the biharmonic equation. A linear superposition of hydrodynamic load and compliant foundation reaction is included. The stiffness of the compliant foundation is modeled as a distributed stiffness that supports the top foil. The system of governing equations is solved numerically by a computer program written in the Mathematica computing environment. Representative calculations and comparisons with experimental results are included for a generation I gas foil thrust bearing.

  4. On the Performance of Pivoted Curved Slider Bearings: Rabinowitsch Fluid Model

    Directory of Open Access Journals (Sweden)

    U.P. Singh

    2012-09-01

    Full Text Available The present theoretical analysis is to investigate the effect of nonNewtonian Pseudoplastic & Dilatant lubricants (lubricant blended with viscosity index improver–Rabinowitsch fluid model on the dynamic stiffness and damping characteristics of pivoted curved slider bearings. The modified Reynolds equation has been obtained for steady and damping states of the bearing. To analyze the steady state characteristics and dynamic characteristics, small perturbation theory has been adopted. The results for the steady state bearing performance characteristics (steady state film pressure, load carrying capacity and centre of pressure as well as dynamic stiffness and damping characteristics have been calculated numerically for various values of viscosity index improver using Mathematical 7.0 and it is concluded that these characteristics vary significantly with the non-Newtonian behavior of the fluid consistent with the real nature of the problem.

  5. An Investigation on the Dynamics of High-Speed Systems Using Nonlinear Analytical Floating Ring Bearing Models

    Directory of Open Access Journals (Sweden)

    Athanasios Chasalevris

    2016-01-01

    Full Text Available The scope of this paper is to investigate the dynamics of a rotor-bearing system of high-speed under recently developed analytical bearing models. The development of a theory that can yield the dynamic response of a high-speed system without short/long bearing approximation and without time-consuming numerical methods for the finite-length bearing model is the outcome of this work. The rotor system is introduced as a rigid body so that the dynamics of the system are influenced only from the nonlinear bearing forces which are introduced with closed form expressions. The outcome is a system of nonlinear equations and its solution produces the dynamic response of the high-speed system using exact analytical solution for the bearing forces. The transient dynamic response of the system is evaluated through the wide range of rotating speed and under different bearing solutions including short bearing approximation, presenting the subsynchronous components that are developed when instabilities occur. Time-frequency analysis of the resulting response time-series is presented and the outcome is compared with that obtained from numerical solution of the bearing lubrication and with the short bearing approximation model.

  6. Research on Degeneration Model of Neural Network for Deep Groove Ball Bearing Based on Feature Fusion

    Directory of Open Access Journals (Sweden)

    Lijun Zhang

    2018-02-01

    Full Text Available Aiming at the pitting fault of deep groove ball bearing during service, this paper uses the vibration signal of five different states of deep groove ball bearing and extracts the relevant features, then uses a neural network to model the degradation for identifying and classifying the fault type. By comparing the effects of training samples with different capacities through performance indexes such as the accuracy and convergence speed, it is proven that an increase in the sample size can improve the performance of the model. Based on the polynomial fitting principle and Pearson correlation coefficient, fusion features based on the skewness index are proposed, and the performance improvement of the model after incorporating the fusion features is also validated. A comparison of the performance of the support vector machine (SVM model and the neural network model on this dataset is given. The research shows that neural networks have more potential for complex and high-volume datasets.

  7. A hybrid feature selection and health indicator construction scheme for delay-time-based degradation modelling of rolling element bearings

    Science.gov (United States)

    Zhang, Bin; Deng, Congying; Zhang, Yi

    2018-03-01

    Rolling element bearings are mechanical components used frequently in most rotating machinery and they are also vulnerable links representing the main source of failures in such systems. Thus, health condition monitoring and fault diagnosis of rolling element bearings have long been studied to improve operational reliability and maintenance efficiency of rotatory machines. Over the past decade, prognosis that enables forewarning of failure and estimation of residual life attracted increasing attention. To accurately and efficiently predict failure of the rolling element bearing, the degradation requires to be well represented and modelled. For this purpose, degradation of the rolling element bearing is analysed with the delay-time-based model in this paper. Also, a hybrid feature selection and health indicator construction scheme is proposed for extraction of the bearing health relevant information from condition monitoring sensor data. Effectiveness of the presented approach is validated through case studies on rolling element bearing run-to-failure experiments.

  8. GNAR-GARCH model and its application in feature extraction for rolling bearing fault diagnosis

    Science.gov (United States)

    Ma, Jiaxin; Xu, Feiyun; Huang, Kai; Huang, Ren

    2017-09-01

    Given its simplicity of modeling and sensitivity to condition variations, time series model is widely used in feature extraction to realize fault classification and diagnosis. However, nonlinear and nonstationary characteristics common in fault signals of rolling bearing bring challenges to the diagnosis. In this paper, a hybrid model, the combination of a general expression for linear and nonlinear autoregressive (GNAR) model and a generalized autoregressive conditional heteroscedasticity (GARCH) model, (i.e., GNAR-GARCH), is proposed and applied to rolling bearing fault diagnosis. An exact expression of GNAR-GARCH model is given. Maximum likelihood method is used for parameter estimation and modified Akaike Information Criterion is adopted for structure identification of GNAR-GARCH model. The main advantage of this novel model over other models is that the combination makes the model suitable for nonlinear and nonstationary signals. It is verified with statistical tests that contain comparisons among the different time series models. Finally, GNAR-GARCH model is applied to fault diagnosis by modeling mechanical vibration signals including simulation and real data. With the parameters estimated and taken as feature vectors, k-nearest neighbor algorithm is utilized to realize the classification of fault status. The results show that GNAR-GARCH model exhibits higher accuracy and better performance than do other models.

  9. A Site Specific Model And Analysis Of The Neutral Somatic Mutation Rate In Whole-Genome Cancer Data

    DEFF Research Database (Denmark)

    Bertl, Johanna; Guo, Qianyun; Rasmussen, Malene Juul

    2017-01-01

    Detailed modelling of the neutral mutational process in cancer cells is crucial for identifying driver mutations and understanding the mutational mechanisms that act during cancer development. The neutral mutational process is very complex: whole-genome analyses have revealed that the mutation ra...

  10. A numerical test method of California bearing ratio on graded crushed rocks using particle flow modeling

    OpenAIRE

    Jiang, Yingjun; Wong, Louis Ngai Yuen; Ren, Jiaolong

    2015-01-01

    In order to better understand the mechanical properties of graded crushed rocks (GCRs) and to optimize the relevant design, a numerical test method based on the particle flow modeling technique PFC2D is developed for the California bearing ratio (CBR) test on GCRs. The effects of different testing conditions and micro-mechanical parameters used in the model on the CBR numerical results have been systematically studied. The reliability of the numerical technique is verified. The numerical resu...

  11. Modelling of Outer and Inner Film Oil Pressure for Floating Ring Bearing Clearance in Turbochargers

    International Nuclear Information System (INIS)

    Zhang Hao; Shi Zhanqun; Gu Fengshou; Ball, Andrew

    2011-01-01

    Floating ring bearing is widely used in turbochargers to undertake the extreme condition of high rotating speed and high operating temperature. It is also the most concerned by the designers and users alike due to its high failure rate and high maintenance cost. Any little clearance change may result in oil leakage, which in turn cause blue smoke or black smoke according to leakage types. However, there is no condition monitoring of this bearing because it is almost impossible to measure the clearance especially the inner clearance, in which the inner oil film directly bears the high speed rotation. In stead of measuring clearance directly, this paper has proposed a method that uses film pressure as a measure to monitor the bearing clearance and its variation. A non-linear mathematical model is developed by using Reynolds equations with non-linear oil film pressure. A full description of the outer and inner film is provided along both axial and radial directions. A numerical simulation is immediately carried out. Variable clearance changes are investigated using the mathematical model. Results show the relationship between clearance and film pressure.

  12. Assessment of Brown Bear\\'s (Ursus arctos syriacus Winter Habitat Using Geographically Weighted Regression and Generalized Linear Model in South of Iran

    Directory of Open Access Journals (Sweden)

    A. A. Zarei

    2016-03-01

    Full Text Available Winter dens are one of the important components of brown bear's (Ursus arctos syriacus habitat, affecting their reproduction and survival. Therefore identification of factors affecting the habitat selection and suitable denning areas in the conservation of our largest carnivore is necessary. We used Geographically Weighted Logistic Regression (GWLR and Generalized Linear Model (GLM for modeling suitability of denning habitat in Kouhkhom region in Fars province. In the present research, 20 dens (presence locations and 20 caves where signs of bear were not found (absence locations were used as dependent variables and six environmental factors were used for each location as independent variables. The results of GLM showed that variables of distance to settlements, altitude, and distance to water were the most important parameters affecting suitability of the brown bear's denning habitat. The results of GWLR showed the significant local variations in the relationship between occurrence of brown bear dens and the variable of distance to settlements. Based on the results of both models, suitable habitats for denning of the species are impassable areas in the mountains and inaccessible for humans.

  13. Simulating polar bear energetics during a seasonal fast using a mechanistic model.

    Directory of Open Access Journals (Sweden)

    Paul D Mathewson

    Full Text Available In this study we tested the ability of a mechanistic model (Niche Mapper™ to accurately model adult, non-denning polar bear (Ursus maritimus energetics while fasting during the ice-free season in the western Hudson Bay. The model uses a steady state heat balance approach, which calculates the metabolic rate that will allow an animal to maintain its core temperature in its particular microclimate conditions. Predicted weight loss for a 120 day fast typical of the 1990s was comparable to empirical studies of the population, and the model was able to reach a heat balance at the target metabolic rate for the entire fast, supporting use of the model to explore the impacts of climate change on polar bears. Niche Mapper predicted that all but the poorest condition bears would survive a 120 day fast under current climate conditions. When the fast extended to 180 days, Niche Mapper predicted mortality of up to 18% for males. Our results illustrate how environmental conditions, variation in animal properties, and thermoregulation processes may impact survival during extended fasts because polar bears were predicted to require additional energetic expenditure for thermoregulation during a 180 day fast. A uniform 3°C temperature increase reduced male mortality during a 180 day fast from 18% to 15%. Niche Mapper explicitly links an animal's energetics to environmental conditions and thus can be a valuable tool to help inform predictions of climate-related population changes. Since Niche Mapper is a generic model, it can make energetic predictions for other species threatened by climate change.

  14. Simulating polar bear energetics during a seasonal fast using a mechanistic model.

    Science.gov (United States)

    Mathewson, Paul D; Porter, Warren P

    2013-01-01

    In this study we tested the ability of a mechanistic model (Niche Mapper™) to accurately model adult, non-denning polar bear (Ursus maritimus) energetics while fasting during the ice-free season in the western Hudson Bay. The model uses a steady state heat balance approach, which calculates the metabolic rate that will allow an animal to maintain its core temperature in its particular microclimate conditions. Predicted weight loss for a 120 day fast typical of the 1990s was comparable to empirical studies of the population, and the model was able to reach a heat balance at the target metabolic rate for the entire fast, supporting use of the model to explore the impacts of climate change on polar bears. Niche Mapper predicted that all but the poorest condition bears would survive a 120 day fast under current climate conditions. When the fast extended to 180 days, Niche Mapper predicted mortality of up to 18% for males. Our results illustrate how environmental conditions, variation in animal properties, and thermoregulation processes may impact survival during extended fasts because polar bears were predicted to require additional energetic expenditure for thermoregulation during a 180 day fast. A uniform 3°C temperature increase reduced male mortality during a 180 day fast from 18% to 15%. Niche Mapper explicitly links an animal's energetics to environmental conditions and thus can be a valuable tool to help inform predictions of climate-related population changes. Since Niche Mapper is a generic model, it can make energetic predictions for other species threatened by climate change.

  15. Vibration Propagation of Gear Dynamics in a Gear-Bearing-Housing System Using Mathematical Modeling and Finite Element Analysis

    Science.gov (United States)

    Parker, Robert G.; Guo, Yi; Eritenel, Tugan; Ericson, Tristan M.

    2012-01-01

    Vibration and noise caused by gear dynamics at the meshing teeth propagate through power transmission components to the surrounding environment. This study is devoted to developing computational tools to investigate the vibro-acoustic propagation of gear dynamics through a gearbox using different bearings. Detailed finite element/contact mechanics and boundary element models of the gear/bearing/housing system are established to compute the system vibration and noise propagation. Both vibration and acoustic models are validated by experiments including the vibration modal testing and sound field measurements. The effectiveness of each bearing type to disrupt vibration propagation is speed-dependent. Housing plays an important role in noise radiation .It, however, has limited effects on gear dynamics. Bearings are critical components in drivetrains. Accurate modeling of rolling element bearings is essential to assess vibration and noise of drivetrain systems. This study also seeks to fully describe the vibro-acoustic propagation of gear dynamics through a power-transmission system using rolling element and fluid film wave bearings. Fluid film wave bearings, which have higher damping than rolling element bearings, could offer an energy dissipation mechanism that reduces the gearbox noise. The effectiveness of each bearing type to disrupt vibration propagation in explored using multi-body computational models. These models include gears, shafts, rolling element and fluid film wave bearings, and the housing. Radiated noise is mapped from the gearbox surface to surrounding environment. The effectiveness of rolling element and fluid film wave bearings in breaking the vibro-acoustic propagation path from the gear to the housing is investigated.

  16. Hydrodynamic bearings

    CERN Document Server

    Bonneau, Dominique; Souchet, Dominique

    2014-01-01

    This Series provides the necessary elements to the development and validation of numerical prediction models for hydrodynamic bearings. This book describes the rheological models and the equations of lubrication. It also presents the numerical approaches used to solve the above equations by finite differences, finite volumes and finite elements methods.

  17. A fully coupled variable properties thermohydraulic model for a cryogenic hydrostatic journal bearing

    Science.gov (United States)

    Braun, M. J.; Wheeler, R. L., III; Hendricks, R. C.

    1986-01-01

    The goal set forth here is to continue the work started by Braun et al. (1984-1985) and present an integrated analysis of the behavior of the two row, 20 staggered pockets, hydrostatic cryogenic bearing used by the turbopumps of the Space Shuttle main engine. The variable properties Reynolds equation is fully coupled with the two-dimensional fluid film energy equation. The three-dimensional equations of the shaft and bushing model the boundary conditions of the fluid film energy equation. The effects of shaft eccentricity, angular velocity, and inertia pressure drops at pocket edge are incorporated in the model. Their effects on the bearing fluid properties, load carrying capacity, mass flow, pressure, velocity, and temperature form the ultimate object of this paper.

  18. Integrated population modeling of black bears in Minnesota: implications for monitoring and management.

    Directory of Open Access Journals (Sweden)

    John R Fieberg

    Full Text Available BACKGROUND: Wildlife populations are difficult to monitor directly because of costs and logistical challenges associated with collecting informative abundance data from live animals. By contrast, data on harvested individuals (e.g., age and sex are often readily available. Increasingly, integrated population models are used for natural resource management because they synthesize various relevant data into a single analysis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the performance of integrated population models applied to black bears (Ursus americanus in Minnesota, USA. Models were constructed using sex-specific age-at-harvest matrices (1980-2008, data on hunting effort and natural food supplies (which affects hunting success, and statewide mark-recapture estimates of abundance (1991, 1997, 2002. We compared this approach to Downing reconstruction, a commonly used population monitoring method that utilizes only age-at-harvest data. We first conducted a large-scale simulation study, in which our integrated models provided more accurate estimates of population trends than did Downing reconstruction. Estimates of trends were robust to various forms of model misspecification, including incorrectly specified cub and yearling survival parameters, age-related reporting biases in harvest data, and unmodeled temporal variability in survival and harvest rates. When applied to actual data on Minnesota black bears, the model predicted that harvest rates were negatively correlated with food availability and positively correlated with hunting effort, consistent with independent telemetry data. With no direct data on fertility, the model also correctly predicted 2-point cycles in cub production. Model-derived estimates of abundance for the most recent years provided a reasonable match to an empirical population estimate obtained after modeling efforts were completed. CONCLUSIONS/SIGNIFICANCE: Integrated population modeling provided a reasonable

  19. Integrated population modeling of black bears in Minnesota: implications for monitoring and management.

    Science.gov (United States)

    Fieberg, John R; Shertzer, Kyle W; Conn, Paul B; Noyce, Karen V; Garshelis, David L

    2010-08-12

    Wildlife populations are difficult to monitor directly because of costs and logistical challenges associated with collecting informative abundance data from live animals. By contrast, data on harvested individuals (e.g., age and sex) are often readily available. Increasingly, integrated population models are used for natural resource management because they synthesize various relevant data into a single analysis. We investigated the performance of integrated population models applied to black bears (Ursus americanus) in Minnesota, USA. Models were constructed using sex-specific age-at-harvest matrices (1980-2008), data on hunting effort and natural food supplies (which affects hunting success), and statewide mark-recapture estimates of abundance (1991, 1997, 2002). We compared this approach to Downing reconstruction, a commonly used population monitoring method that utilizes only age-at-harvest data. We first conducted a large-scale simulation study, in which our integrated models provided more accurate estimates of population trends than did Downing reconstruction. Estimates of trends were robust to various forms of model misspecification, including incorrectly specified cub and yearling survival parameters, age-related reporting biases in harvest data, and unmodeled temporal variability in survival and harvest rates. When applied to actual data on Minnesota black bears, the model predicted that harvest rates were negatively correlated with food availability and positively correlated with hunting effort, consistent with independent telemetry data. With no direct data on fertility, the model also correctly predicted 2-point cycles in cub production. Model-derived estimates of abundance for the most recent years provided a reasonable match to an empirical population estimate obtained after modeling efforts were completed. Integrated population modeling provided a reasonable framework for synthesizing age-at-harvest data, periodic large-scale abundance estimates, and

  20. A Generic Friction Model for Radial Slider Bearing Simulation Considering Elastic and Plastic Deformation

    Directory of Open Access Journals (Sweden)

    Günter Offner

    2015-06-01

    Full Text Available The investigation of component dynamics is one of the main tasks of internal combustion engine (ICE simulation. This prediction is important in order to understand complex loading conditions, which happen in a running ICE. Due to the need for fuel saving, mechanical friction, in particular in radial slider bearings, is one important investigation target. A generic friction modeling approach for radial slider bearings, which can be applied to lubricated contact regimes, will be presented in this paper. Besides viscous friction, the approach considers in particular boundary friction. The parameterization of the friction model is done using surface material and surface roughness measurement data. Furthermore, fluid properties depending on the applied oil additives are being considered. The application of the model will be demonstrated for a typical engineering task of a connecting rod big end study to outline the effects of contact surface texture. AlSn-based and polymer coated bearing shells will be analyzed and compared with respect to friction reduction effects, running-in behavior and thermal load capabilities.

  1. Protein model discrimination using mutational sensitivity derived from deep sequencing.

    Science.gov (United States)

    Adkar, Bharat V; Tripathi, Arti; Sahoo, Anusmita; Bajaj, Kanika; Goswami, Devrishi; Chakrabarti, Purbani; Swarnkar, Mohit K; Gokhale, Rajesh S; Varadarajan, Raghavan

    2012-02-08

    A major bottleneck in protein structure prediction is the selection of correct models from a pool of decoys. Relative activities of ∼1,200 individual single-site mutants in a saturation library of the bacterial toxin CcdB were estimated by determining their relative populations using deep sequencing. This phenotypic information was used to define an empirical score for each residue (RankScore), which correlated with the residue depth, and identify active-site residues. Using these correlations, ∼98% of correct models of CcdB (RMSD ≤ 4Å) were identified from a large set of decoys. The model-discrimination methodology was further validated on eleven different monomeric proteins using simulated RankScore values. The methodology is also a rapid, accurate way to obtain relative activities of each mutant in a large pool and derive sequence-structure-function relationships without protein isolation or characterization. It can be applied to any system in which mutational effects can be monitored by a phenotypic readout. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Dynamic Model for Hydro-Turbine Generator Units Based on a Database Method for Guide Bearings

    Directory of Open Access Journals (Sweden)

    Yong Xu

    2013-01-01

    Full Text Available A suitable dynamic model of rotor system is of great significance not only for supplying knowledge of the fault mechanism, but also for assisting in machine health monitoring research. Many techniques have been developed for properly modeling the radial vibration of large hydro-turbine generator units. However, an applicable dynamic model has not yet been reported in literature due to the complexity of the boundary conditions and exciting forces. In this paper, a finite element (FE rotor dynamic model of radial vibration taking account of operating conditions is proposed. A brief and practical database method is employed to model the guide bearing. Taking advantage of the method, rotating speed and bearing clearance can be considered in the model. A novel algorithm, which can take account of both transient and steady-state analysis, is proposed to solve the model. Dynamic response for rotor model of 125 MW hydro-turbine generator units in Gezhouba Power Station is simulated. Field data from Optimal Maintenance Information System for Hydro power plants (HOMIS are analyzed compared with the simulation. Results illustrate the application value of the model in providing knowledge of the fault mechanism and in failure diagnosis.

  3. Witches' brooms in Siberian stone pine as somatic mutations and initial genetic material for breeding of nut-bearing and ornamental cultivars

    Directory of Open Access Journals (Sweden)

    M. S. Yamburov

    2013-12-01

    Full Text Available For the raising of the Siberian stone pine (Pinus sibirica Du Tour nut-bearing and ornamental cultivars, the most important traits are adense crown, slow growth and precocity. Generative mutations of this kind are eliminated by natural selection, therefore, somatic mutationrsearch is important. Among somatic mutations, the most promising one is the so-called 'witches' brooms' (WB where crown fragments demonstrate slowed growth and intensive branching. WB occasionally occurs in native populations. According to phytopathology textbooks, WB are caused by various pathogen species (viruses, mycoplasmas, fungi. The WB of this kind are characterized by a sickly look, full suppression of reproductive functions, a short life and a nidus patternof distribution. There are also WB of different types: with a high vitality and fertility, a long life and sporadic distribution. They occur very rarely(about 1 per 10 000 trees across the species' range. We investigated 18 trees with WB of this type. The size of WB ranged from 0.3 to 30 m, age varied from 30 to 300 years. Male cones were absent inall WB. Female cone initiation was normal if the WB was located in the top part of a crown. Scions from WB and a normal crown (NC of the same tree were grafted on identical rootstocks. On average,the height of 7-year-old WB grafts (WBG was 2 times lower, and the stem diameter was 2 times higher than in the NC grafts (NCG. It wasachieved due to the fundamental differences in the shoot system morphogenesis. Here are three principal differences in decreasing order of importance: (i WBGs were characterized by the absence or near absence of apical dominance. The NCG had no more than 3 orders of branching, and the length of the 1st order axis was on average 5times larger than the axis of the 3rd order. The WBG had 6-7 orders of branching, and the length of shoots of 5-6th orders averaged 80-90% of the length of the first orders. (ii At an

  4. Modeling evolutionary dynamics of epigenetic mutations in hierarchically organized tumors.

    Directory of Open Access Journals (Sweden)

    Andrea Sottoriva

    2011-05-01

    Full Text Available The cancer stem cell (CSC concept is a highly debated topic in cancer research. While experimental evidence in favor of the cancer stem cell theory is apparently abundant, the results are often criticized as being difficult to interpret. An important reason for this is that most experimental data that support this model rely on transplantation studies. In this study we use a novel cellular Potts model to elucidate the dynamics of established malignancies that are driven by a small subset of CSCs. Our results demonstrate that epigenetic mutations that occur during mitosis display highly altered dynamics in CSC-driven malignancies compared to a classical, non-hierarchical model of growth. In particular, the heterogeneity observed in CSC-driven tumors is considerably higher. We speculate that this feature could be used in combination with epigenetic (methylation sequencing studies of human malignancies to prove or refute the CSC hypothesis in established tumors without the need for transplantation. Moreover our tumor growth simulations indicate that CSC-driven tumors display evolutionary features that can be considered beneficial during tumor progression. Besides an increased heterogeneity they also exhibit properties that allow the escape of clones from local fitness peaks. This leads to more aggressive phenotypes in the long run and makes the neoplasm more adaptable to stringent selective forces such as cancer treatment. Indeed when therapy is applied the clone landscape of the regrown tumor is more aggressive with respect to the primary tumor, whereas the classical model demonstrated similar patterns before and after therapy. Understanding these often counter-intuitive fundamental properties of (non-hierarchically organized malignancies is a crucial step in validating the CSC concept as well as providing insight into the therapeutical consequences of this model.

  5. Analysis of HD Journal Bearings Considering Elastic Deformation and Non-Newtonian Rabinowitsch Fluid Model

    Directory of Open Access Journals (Sweden)

    J. Javorova

    2016-06-01

    Full Text Available The purpose of this paper is to study the performance of a finite length journal bearing, taking into account effects of non-Newtonian Rabinowitsch flow rheology and elastic deformations of the bearing liner. According to the Rabinowitsch fluid model, the cubic-stress constitutive equation is used to account for the non-Newtonian effects of pseudoplastic and dilatant lubricants. Integrating the continuity equation across the film, the nonlinear non-Newtonian Reynolds-type equation is derived. The elasticity part of the problem is solved on the base of Vlassov model of an elastic foundation. The numerical solution of the modified Reynolds equation is carried out by using FDM with over-relaxation technique. The results for steady state bearing performance characteristics have been calculated for various values of nonlinear factor and elasticity parameters. It was concluded that in comparison with the Newtonian lubricants, higher values of film pressure and load carrying capacity have been obtained for dilatant lubricants, while the case was reversed for pseudoplastic lubricants.

  6. Depression of p53-independent Akt survival signals in human oral cancer cells bearing mutated p53 gene after exposure to high-LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Yosuke [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Takahashi, Akihisa [Advanced Scientific Research Leader Development Unit, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Kajihara, Atsuhisa; Yamakawa, Nobuhiro; Imai, Yuichiro [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ota, Ichiro; Okamoto, Noritomo [Department of Otorhinolaryngology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Mori, Eiichiro [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Noda, Taichi [Department of Dermatology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Furusawa, Yoshiya [Heavy-ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kirita, Tadaaki [Department of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ohnishi, Takeo, E-mail: tohnishi@naramed-u.ac.jp [Department of Radiation Oncology, School of Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer High-LET radiation induces efficiently apoptosis regardless of p53 gene status. Black-Right-Pointing-Pointer We examined whether high-LET radiation depresses the Akt-survival signals. Black-Right-Pointing-Pointer High-LET radiation depresses of survival signals even in the mp53 cancer cells. Black-Right-Pointing-Pointer High-LET radiation activates Caspase-9 through depression of survival signals. Black-Right-Pointing-Pointer High-LET radiation suppresses cell growth through depression of survival signals. -- Abstract: Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independent apoptosis takes place through the activation of Caspase-9 which results in the cleavage of Caspase-3 and poly (ADP-ribose) polymerase (PARP). This study was designed to examine if high-LET radiation depresses serine/threonine protein kinase B (PKB, also known as Akt) and Akt-related proteins. Human gingival cancer cells (Ca9-22 cells) harboring a mutated p53 (mp53) gene were irradiated with 2 Gy of X-rays or Fe-ion beams. The cellular contents of Akt-related proteins participating in cell survival signaling were analyzed with Western Blotting 1, 2, 3 and 6 h after irradiation. Cell cycle distributions after irradiation were assayed with flow cytometric analysis. Akt-related protein levels decreased when cells were irradiated with high-LET radiation. High-LET radiation increased G{sub 2}/M phase arrests and suppressed the progression of the cell cycle much more efficiently when compared to low-LET radiation. These results suggest that high-LET radiation enhances apoptosis through the activation of Caspase-3 and Caspase-9, and suppresses cell growth by suppressing Akt-related signaling, even in mp

  7. A constitutive mechanical model for gas hydrate bearing sediments incorporating inelastic mechanisms

    KAUST Repository

    Sánchez, Marcelo

    2016-11-30

    Gas hydrate bearing sediments (HBS) are natural soils formed in permafrost and sub-marine settings where the temperature and pressure conditions are such that gas hydrates are stable. If these conditions shift from the hydrate stability zone, hydrates dissociate and move from the solid to the gas phase. Hydrate dissociation is accompanied by significant changes in sediment structure and strongly affects its mechanical behavior (e.g., sediment stiffenss, strength and dilatancy). The mechanical behavior of HBS is very complex and its modeling poses great challenges. This paper presents a new geomechanical model for hydrate bearing sediments. The model incorporates the concept of partition stress, plus a number of inelastic mechanisms proposed to capture the complex behavior of this type of soil. This constitutive model is especially well suited to simulate the behavior of HBS upon dissociation. The model was applied and validated against experimental data from triaxial and oedometric tests conducted on manufactured and natural specimens involving different hydrate saturation, hydrate morphology, and confinement conditions. Particular attention was paid to model the HBS behavior during hydrate dissociation under loading. The model performance was highly satisfactory in all the cases studied. It managed to properly capture the main features of HBS mechanical behavior and it also assisted to interpret the behavior of this type of sediment under different loading and hydrate conditions.

  8. Textile solar light collectors based on models for polar bear hair

    Energy Technology Data Exchange (ETDEWEB)

    Bahners, Thomas; Schlosser, Uwe; Schollmeyer, Eckhard [Deutsches Textilforschungszentrum Nord-West e.V., Adlerstr. 1, D-47798 Krefeld (Germany); Gutmann, Rainer [Institut fuer Textilchemie und Chemiefasern, Koerschtalstr. 26, D-73770 Denkendorf (Germany)

    2008-12-15

    Concepts of technical fibers following models for the polar bear hair to be used for textile solar collectors are discussed. The approach to coat fibers with a thin layer into which fluorescent dyestuff was dispersed was studied experimentally. Modified fibers made of different polymers were characterized with respect to optical properties relevant for the bionic model. In the case of poly(methylmethacrylate) fibers, the envisaged effect could be achieved to high efficiency. The optical performance could be enhanced by ultrasonic dispersion of the dyestuff in the coating matrix. The effect is less significant in semi-crystalline fibers such as poly(ethylene terephthalate), which is attributed to diffuse scattering. (author)

  9. Comparison of Models for the Steady-State Analysis of Tilting-Pad Thrust Bearings

    DEFF Research Database (Denmark)

    Heinrichson, Niels; Santos, Ilmar

    2005-01-01

    distribution the deflection of the pad due to pressure and thermal bending can be calculated using a flat plate approximation. At the five free sides of the pad heat transfer can be modelled. The temperature distribution at the inlet to the pad can be calculated through equilibrium of thermal energy...... for the groove between pads and the oil bath temperature from energy equilibrium for the entire bearing. The main theoretical contribution of this paper is the elaboration and comparison of 7 different mathematical models of increasing complexity. The results are compared to experimental data for steady...

  10. Research on analytical model and design formulas of permanent magnetic bearings based on Halbach array with arbitrary segmented magnetized angle

    International Nuclear Information System (INIS)

    Wang, Nianxian; Wang, Dongxiong; Chen, Kuisheng; Wu, Huachun

    2016-01-01

    The bearing capacity of permanent magnetic bearings can be improved efficiently by using the Halbach array magnetization. However, the research on analytical model of Halbach array PMBs with arbitrary segmented magnetized angle has not been developed. The application of Halbach array PMBs has been limited by the absence of the analytical model and design formulas. In this research, the Halbach array PMBs with arbitrary segmented magnetized angle has been studied. The magnetization model of bearings is established. The magnetic field distribution model of the permanent magnet array is established by using the scalar magnetic potential model. On the basis of this, the bearing force model and the bearing stiffness model of the PMBs are established based on the virtual displacement method. The influence of the pair of magnetic rings in one cycle and the structure parameters of PMBs on the maximal bearing capacity and support stiffness characteristics are studied. The reference factors for the design process of PMBs have been given. Finally, the theoretical model and the conclusions are verified by the finite element analysis.

  11. Identification of High-Impact cis-Regulatory Mutations Using Transcription Factor Specific Random Forest Models.

    Directory of Open Access Journals (Sweden)

    Dmitry Svetlichnyy

    2015-11-01

    Full Text Available Cancer genomes contain vast amounts of somatic mutations, many of which are passenger mutations not involved in oncogenesis. Whereas driver mutations in protein-coding genes can be distinguished from passenger mutations based on their recurrence, non-coding mutations are usually not recurrent at the same position. Therefore, it is still unclear how to identify cis-regulatory driver mutations, particularly when chromatin data from the same patient is not available, thus relying only on sequence and expression information. Here we use machine-learning methods to predict functional regulatory regions using sequence information alone, and compare the predicted activity of the mutated region with the reference sequence. This way we define the Predicted Regulatory Impact of a Mutation in an Enhancer (PRIME. We find that the recently identified driver mutation in the TAL1 enhancer has a high PRIME score, representing a "gain-of-target" for MYB, whereas the highly recurrent TERT promoter mutation has a surprisingly low PRIME score. We trained Random Forest models for 45 cancer-related transcription factors, and used these to score variations in the HeLa genome and somatic mutations across more than five hundred cancer genomes. Each model predicts only a small fraction of non-coding mutations with a potential impact on the function of the encompassing regulatory region. Nevertheless, as these few candidate driver mutations are often linked to gains in chromatin activity and gene expression, they may contribute to the oncogenic program by altering the expression levels of specific oncogenes and tumor suppressor genes.

  12. Investigation of the velocity distribution in the flow of a journal bearing model

    Science.gov (United States)

    Nobis, Matthias; Reinke, Peter; Schmidt, Marcus; Riedel, Marco; Redlich, Marcel

    2014-03-01

    In many previous studies the main focus was put on the pressure distribution in the lubricating gap. Due to the limited space in the gap an investigation of the velocity distribution is very difficult or rather impossible. Based on the geometrical shapes of a real journal bearing, a bearing model test rig with an increased relative gap width has been developed. Thus, it is possible to detect the distribution of the flow speed within the gap by using a Laser Doppler Velocimeter (LDV). The comparability of the flow to the flow in a real journal bearing is ensured by observing the Reynolds similarity. Due to a targeted eccentricity in the system and the circumferential groove over 180°, there is in connection with the outlet hole in the rotating shaft a permanent change in the outflow conditions. The consequence is a periodically varying system pressure with effects to the pressure and volumetric flow rate at the inlet and outlet. The velocity measurements with a triggered LDV are done by considering these transient boundary conditions at the system boundaries. In this paper the experimental setup, the expiration of the investigations and some exemplary results are presented. Attendant to the experiment, numerical simulations are carried out and the results are compared with the experimental data.

  13. Investigation of the velocity distribution in the flow of a journal bearing model

    Directory of Open Access Journals (Sweden)

    Nobis Matthias

    2014-03-01

    Full Text Available In many previous studies the main focus was put on the pressure distribution in the lubricating gap. Due to the limited space in the gap an investigation of the velocity distribution is very difficult or rather impossible. Based on the geometrical shapes of a real journal bearing, a bearing model test rig with an increased relative gap width has been developed. Thus, it is possible to detect the distribution of the flow speed within the gap by using a Laser Doppler Velocimeter (LDV. The comparability of the flow to the flow in a real journal bearing is ensured by observing the Reynolds similarity. Due to a targeted eccentricity in the system and the circumferential groove over 180°, there is in connection with the outlet hole in the rotating shaft a permanent change in the outflow conditions. The consequence is a periodically varying system pressure with effects to the pressure and volumetric flow rate at the inlet and outlet. The velocity measurements with a triggered LDV are done by considering these transient boundary conditions at the system boundaries. In this paper the experimental setup, the expiration of the investigations and some exemplary results are presented. Attendant to the experiment, numerical simulations are carried out and the results are compared with the experimental data.

  14. Numerical modelling of the flow in the annular multi-recess hydrostatic thrust bearing using CFD methods

    Directory of Open Access Journals (Sweden)

    Drbáková S.

    2013-04-01

    Full Text Available The current research of hydrostatic bearings and hydrostatic slide-ways is far from being over. The topic is constantly evolving, creating new geometries of the sliding bearings, developing new types of friction materials and lubricants. The control elements of hydraulic mechanisms that serve to regulation of the hydrostatic bearings tipping are still in progress. Almost every application has different requirements for the bearings, whether in terms of loading capacity, speed rotation, and also the price. All these aspects should be included in the design of hydrostatic thrust bearings. Thanks to great advances in the development of computer technology and software for numerical modelling, we can simulate real movement of viscous fluids. To create a numerical model of hydrostatic thrust bearing, Ansys Fluent 14.0 software package has been applied. The article describes the basic methods of numerical modelling of the given problem and evaluates the pressure field and the loading capacity of annular multi-recess hydrostatic thrust bearing and its dependence on the change in static pressure.

  15. A Canine Non-Weight-Bearing Model with Radial Neurectomy for Rotator Cuff Repair.

    Directory of Open Access Journals (Sweden)

    Xiaoxi Ji

    Full Text Available The major concern of using a large animal model to study rotator cuff repair is the high rate of repair retears. The purpose of this study was to test a non-weight-bearing (NWB canine model for rotator cuff repair research.First, in the in vitro study, 18 shoulders were randomized to 3 groups. 1 Full-width transections repaired with modified Mason-Allen sutures using 3-0 polyglactin suture, 2 Group 1 repaired using number 2 (#2 polyester braid and long-chain polyethylene suture, and 3 Partial-width transections leaving the superior 2 mm infraspinatus tendon intact without repair. In the in vivo study of 6 dogs, the infraspinatus tendon was partially transected as the same as the in vitro group 3. A radial neurectomy was performed to prevent weight bearing. The operated limb was slung in a custom-made jacket for 6 weeks.In the in vitro study, mean ultimate tensile load and stiffness in Group 2 were significantly higher than Group 1 and 3 (p<0.05. In the in vivo study, gross inspection and histology showed that the preserved superior 2-mm portion of the infraspinatus tendon remained intact with normal structure.Based on the biomechanical and histological findings, this canine NWB model may be an appropriate and useful model for studies of rotator cuff repair.

  16. Verification and improvement of analytical modeling of seismic isolation bearings and isolated structures

    International Nuclear Information System (INIS)

    Forni, M.; La Grotteria, M.; Martelli, A.; Bertola, S.; Bettinali, F.; Dusi, A.; Bergamo, G.; Bonacina, G.

    2002-01-01

    Due to the complexity of dynamic behaviour of seismic isolation (SI) devices, high cost of their tests and non-negligible number of devices having excellent potential for nuclear applications, several countries judged of great interest to extend validation of their numerical models of such devices to the analysis of experimental data obtained by others. Thus, a four-years Coordinated Research Program (CRP) on Intercomparison of Analysis Methods for Isolated Nuclear Structures, proposed by ENEA (1995), was endorsed by the IAEA in 1995. There, Italy was jointly represented by ENEA, ENEL and ISMES, and supplied test results concerning both High Damping Rubber Bearings (HDRBs) and the MISS (Model of Isolated Steel Structure) mock-up, which had been isolated using such bearings. Test data provided by Italy to the other countries were also re-analysed to improve mathematical models. Aim of this final report is to summarise, after a brief description of the devices and structures considered, the most important results and conclusions of the numerical analyses carried out by Italy. For more detailed information, especially as far as the execution of the tests and the implementation of the numerical models are concerned, please refer to the technical reports presented by Italy to the Research Coordination Meetings (RCMs). (author)

  17. Modeling Population-Level Consequences of Polychlorinated Biphenyl Exposure in East Greenland Polar Bears.

    Science.gov (United States)

    Pavlova, Viola; Grimm, Volker; Dietz, Rune; Sonne, Christian; Vorkamp, Katrin; Rigét, Frank F; Letcher, Robert J; Gustavson, Kim; Desforges, Jean-Pierre; Nabe-Nielsen, Jacob

    2016-01-01

    Polychlorinated biphenyls (PCBs) can cause endocrine disruption, cancer, immunosuppression, or reproductive failure in animals. We used an individual-based model to explore whether and how PCB-associated reproductive failure could affect the dynamics of a hypothetical polar bear (Ursus maritimus) population exposed to PCBs to the same degree as the East Greenland subpopulation. Dose-response data from experimental studies on a surrogate species, the mink (Mustela vision), were used in the absence of similar data for polar bears. Two alternative types of reproductive failure in relation to maternal sum-PCB concentrations were considered: increased abortion rate and increased cub mortality. We found that the quantitative impact of PCB-induced reproductive failure on population growth rate depended largely on the actual type of reproductive failure involved. Critical potencies of the dose-response relationship for decreasing the population growth rate were established for both modeled types of reproductive failure. Comparing the model predictions of the age-dependent trend of sum-PCBs concentrations in females with actual field measurements from East Greenland indicated that it was unlikely that PCB exposure caused a high incidence of abortions in the subpopulation. However, on the basis of this analysis, it could not be excluded that PCB exposure contributes to higher cub mortality. Our results highlight the necessity for further research on the possible influence of PCBs on polar bear reproduction regarding their physiological pathway. This includes determining the exact cause of reproductive failure, i.e., in utero exposure versus lactational exposure of offspring; the timing of offspring death; and establishing the most relevant reference metrics for the dose-response relationship.

  18. A Model-level Mutation Tool to Support the Assessment of the Test Case Quality

    NARCIS (Netherlands)

    Condori Fernandez, Nelly; Granda, Maria Fernanda; Vos, Tanja E.J.; Pastor, Oscar; Gołuchowski, M.; Pańkowska, C.; Linger, H.; Schneider, C.

    2016-01-01

    Although mutation testing is a well-known technique for assessing the quality of tests, there is not a lot of support available for model-level mutation analysis. It is also considered to be expensive due to: (i) the large number of mutants generated; ii) the time-consuming activity of determining

  19. Mouse models of NPM1-mutated acute myeloid leukemia: biological and clinical implications.

    Science.gov (United States)

    Sportoletti, P; Varasano, E; Rossi, R; Mupo, A; Tiacci, E; Vassiliou, G; Martelli, M P; Falini, B

    2015-02-01

    Acute myeloid leukemia (AML) carrying nucleophosmin (NPM1) mutations displays distinct biological and clinical features that led to its inclusion as a provisional disease entity in the 2008 World Health Organization (WHO) classification of myeloid neoplasms. Studies of the molecular mechanisms underlying the pathogenesis of NPM1-mutated AML have benefited greatly from several mouse models of this leukemia developed over the past few years. Immunocompromised mice xenografted with NPM1-mutated AML served as the first valuable tool for defining the biology of the disease in vivo. Subsequently, genetically engineered mouse models of the NPM1 mutation, including transgenic and knock-in alleles, allowed the generation of mice with a constant genotype and a reproducible phenotype. These models have been critical for investigating the nature of the molecular effects of these mutations, defining the function of leukemic stem cells in NPM1-mutated AML, identifying chemoresistant preleukemic hemopoietic stem cells and unraveling the key molecular events that cooperate with NPM1 mutations to induce AML in vivo. Moreover, they can serve as a platform for the discovery and validation of new antileukemic drugs in vivo. Advances derived from the analysis of these mouse models promise to greatly accelerate the development of new molecularly targeted therapies for patients with NPM1-mutated AML.

  20. Comparison of Perturbed Reynolds Equation and CFD Models for the Prediction of Dynamic Coefficients of Sliding Bearings

    Directory of Open Access Journals (Sweden)

    Troy Snyder

    2018-01-01

    Full Text Available The accuracy and utility of rotordynamic models for machinery systems are greatly affected by the accuracy of the constituent dynamic bearing models. Primarily, the dynamic behavior of bearings is modeled as linear combination of mass, damping, and stiffness coefficients that are predicted from a perturbed Reynolds equation. In the present paper, an alternative method using Computational Fluid Dynamics (CFD with a moving boundary is used to predict the dynamic coefficients of slider bearings and the results are compared with the more commonly employed perturbed Reynolds equation model. A linear slider bearing geometry is investigated and the results serve as precursors to similar investigations involving the more complex journal bearing geometries. Time and frequency domain methods for the estimation of dynamic coefficients are shown to give comparable results. For CFD with a moving boundary, temporal inertia is found to have a significant effect for a reduced, squeeze Reynolds number less than one. The temporal inertia effect is captured through an added mass coefficient within the dynamic model of the bearing.

  1. MODELING OF SOIL LOAD-BEARING CAPACITY AS A FUNCTION OF SOIL MECHANICAL RESISTANCE TO PENETRATION

    Directory of Open Access Journals (Sweden)

    Cícero Ortigara

    2015-08-01

    Full Text Available Estimation of soil load-bearing capacity from mathematical models that relate preconsolidation pressure (σp to mechanical resistance to penetration (PR and gravimetric soil water content (U is important for defining strategies to prevent compaction of agricultural soils. Our objective was therefore to model the σp and compression index (CI according to the PR (with an impact penetrometer in the field and a static penetrometer inserted at a constant rate in the laboratory and U in a Rhodic Eutrudox. The experiment consisted of six treatments: no-tillage system (NT; NT with chiseling; and NT with additional compaction by combine traffic (passing 4, 8, 10, and 20 times. Soil bulk density, total porosity, PR (in field and laboratory measurements, U, σp, and CI values were determined in the 5.5-10.5 cm and 13.5-18.5 cm layers. Preconsolidation pressure (σp and CI were modeled according to PR in different U. The σp increased and the CI decreased linearly with increases in the PR values. The correlations between σp and PR and PR and CI are influenced by U. From these correlations, the soil load-bearing capacity and compaction susceptibility can be estimated by PR readings evaluated in different U.

  2. Harvesting wildlife affected by climate change: a modelling and management approach for polar bears

    Science.gov (United States)

    Regehr, Eric V.; Wilson, Ryan R.; Rode, Karyn D.; Runge, Michael C.; Stern, Harry

    2017-01-01

    The conservation of many wildlife species requires understanding the demographic effects of climate change, including interactions between climate change and harvest, which can provide cultural, nutritional or economic value to humans.We present a demographic model that is based on the polar bear Ursus maritimus life cycle and includes density-dependent relationships linking vital rates to environmental carrying capacity (K). Using this model, we develop a state-dependent management framework to calculate a harvest level that (i) maintains a population above its maximum net productivity level (MNPL; the population size that produces the greatest net increment in abundance) relative to a changing K, and (ii) has a limited negative effect on population persistence.Our density-dependent relationships suggest that MNPL for polar bears occurs at approximately 0·69 (95% CI = 0·63–0·74) of K. Population growth rate at MNPL was approximately 0·82 (95% CI = 0·79–0·84) of the maximum intrinsic growth rate, suggesting relatively strong compensation for human-caused mortality.Our findings indicate that it is possible to minimize the demographic risks of harvest under climate change, including the risk that harvest will accelerate population declines driven by loss of the polar bear's sea-ice habitat. This requires that (i) the harvest rate – which could be 0 in some situations – accounts for a population's intrinsic growth rate, (ii) the harvest rate accounts for the quality of population data (e.g. lower harvest when uncertainty is large), and (iii) the harvest level is obtained by multiplying the harvest rate by an updated estimate of population size. Environmental variability, the sex and age of removed animals and risk tolerance can also affect the harvest rate.Synthesis and applications. We present a coupled modelling and management approach for wildlife that accounts for climate change and can be used to balance trade-offs among multiple

  3. Harvesting wildlife affected by climate change: a modelling and management approach for polar bears.

    Science.gov (United States)

    Regehr, Eric V; Wilson, Ryan R; Rode, Karyn D; Runge, Michael C; Stern, Harry L

    2017-10-01

    The conservation of many wildlife species requires understanding the demographic effects of climate change, including interactions between climate change and harvest, which can provide cultural, nutritional or economic value to humans.We present a demographic model that is based on the polar bear Ursus maritimus life cycle and includes density-dependent relationships linking vital rates to environmental carrying capacity ( K ). Using this model, we develop a state-dependent management framework to calculate a harvest level that (i) maintains a population above its maximum net productivity level (MNPL; the population size that produces the greatest net increment in abundance) relative to a changing K , and (ii) has a limited negative effect on population persistence.Our density-dependent relationships suggest that MNPL for polar bears occurs at approximately 0·69 (95% CI = 0·63-0·74) of K . Population growth rate at MNPL was approximately 0·82 (95% CI = 0·79-0·84) of the maximum intrinsic growth rate, suggesting relatively strong compensation for human-caused mortality.Our findings indicate that it is possible to minimize the demographic risks of harvest under climate change, including the risk that harvest will accelerate population declines driven by loss of the polar bear's sea-ice habitat. This requires that (i) the harvest rate - which could be 0 in some situations - accounts for a population's intrinsic growth rate, (ii) the harvest rate accounts for the quality of population data (e.g. lower harvest when uncertainty is large), and (iii) the harvest level is obtained by multiplying the harvest rate by an updated estimate of population size. Environmental variability, the sex and age of removed animals and risk tolerance can also affect the harvest rate. Synthesis and applications . We present a coupled modelling and management approach for wildlife that accounts for climate change and can be used to balance trade-offs among multiple conservation

  4. PlayDoh and Toothpicks and Gummy Bears... OH MY, They're Models!

    Science.gov (United States)

    Kolandaivelu, K. P.; Wilson, M. W.; Glesener, G. B.

    2017-12-01

    Simple, everyday items found around the house are often used in geoscience lab activities. Gummy bears and silly putty can model the bending and breaking behaviour of rocks; shaking buildings during an earthquake can be modeled with some Jello, toothpicks, and marshmallows; PlayDoh can be used to demonstrate layers of sedimentary rocks; and even plumbing pipes filled with pebbles and playground sand become miniature physical models of aquifers. When performed correctly, these activities can help students visualize geoscience phenomena or increase students' motivation to pay attention in class, but how do these activities help students develop ways to think like a scientist? "Developing and using models" is one of the important science and engineering practices recommended in the Next Generation Science Standards (NGSS). In this presentation, we will demonstrate a variety of common geoscience lab activities using simple, everyday household items in order to describe ways instructors can help their students develop model-based reasoning skills. Specific areas of interest will be on identifying positive and negative attributes of a model, ways to evaluate the reliability of a model, and how a model can be revised to improve its outcome. We will also outline other kinds of models that can be generated from these lab activities, such as mathematical, graphical, and verbal models. Our goal is to encourage educators to focus more time on helping students develop model-based reasoning skills, which can be used in almost all aspects of everyday life.

  5. Modeling of NOx Destruction Options for INEEL Sodium-Bearing Waste Vitrification

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Richard Arthur

    2001-09-01

    Off-gas NOx concentrations in the range of 1-5 mol% are expected as a result of the proposed vitrification of sodium-bearing waste at the Idaho National Engineering and Environmental Laboratory. An existing kinetic model for staged combustion (originally developed for NOx abatement from the calcination process) was updated for application to vitrification offgas. In addition, two new kinetic models were developed to assess the feasibility of using selective non-catalytic reduction (SNCR) or high-temperature alone for NOx abatement. Each of the models was developed using the Chemkin code. Results indicate that SNCR is a viable option, reducing NOx levels to below 1000 ppmv. In addition, SNCR may be capable of simultaneously reducing CO emissions to below 100 ppmv. Results for using high-temperature alone were not as promising, indicating that a minimum NOx concentration of 3950 ppmv is achievable at 3344°F.

  6. Numerical Modelling and Analysis of Hydrostatic Thrust Air Bearings for High Loading Capacities and Low Air Consumption

    Science.gov (United States)

    Yu, Yunluo; Pu, Guang; Jiang, Kyle

    2017-12-01

    The paper presents a numerical simulation study on hydrostatic thrust air bearings to assess the load capacity, compressed air consumptions, and the dynamic response. Finite Difference Method (FDM) and Finite Volume Method (FVM) are combined to solve the non-linear Reynolds equation to find the pressure distribution of the air bearing gas film and the total loading capacity of the bearing. The influence of design parameters on air film gap characteristics, including the air film thickness, supplied pressure, depth of the groove and external load, are investigated based on the proposed FDM model. The simulation results show that the thrust air bearings with a groove have a higher load capacity and air consumption than without a groove, and the load capacity and air consumption both increase with the depth of the groove. Bearings without the groove are better damped than those with the grooves, and the stability of thrust bearing decreases when the groove depth increases. The stability of the thrust bearings is also affected by their loading.

  7. Bearing system

    Science.gov (United States)

    Kapich, Davorin D.

    1987-01-01

    A bearing system includes backup bearings for supporting a rotating shaft upon failure of primary bearings. In the preferred embodiment, the backup bearings are rolling element bearings having their rolling elements disposed out of contact with their associated respective inner races during normal functioning of the primary bearings. Displacement detection sensors are provided for detecting displacement of the shaft upon failure of the primary bearings. Upon detection of the failure of the primary bearings, the rolling elements and inner races of the backup bearings are brought into mutual contact by axial displacement of the shaft.

  8. Composite model to reproduce the mechanical behaviour of methane hydrate bearing soils

    Science.gov (United States)

    De la Fuente, Maria

    2016-04-01

    Methane hydrate bearing sediments (MHBS) are naturally-occurring materials containing different components in the pores that may suffer phase changes under relative small temperature and pressure variations for conditions typically prevailing a few hundreds of meters below sea level. Their modelling needs to account for heat and mass balance equations of the different components, and several strategies already exist to combine them (e.g., Rutqvist & Moridis, 2009; Sánchez et al. 2014). These equations have to be completed by restrictions and constitutive laws reproducing the phenomenology of heat and fluid flows, phase change conditions and mechanical response. While the formulation of the non-mechanical laws generally includes explicitly the mass fraction of methane in each phase, which allows for a natural update of parameters during phase changes, mechanical laws are, in most cases, stated for the whole solid skeleton (Uchida et al., 2012; Soga et al. 2006). In this paper, a mechanical model is proposed to cope with the response of MHBS. It is based on a composite approach that allows defining the thermo-hydro-mechanical response of mineral skeleton and solid hydrates independently. The global stress-strain-temperature response of the solid phase (grains + hydrate) is then obtained by combining both responses according to energy principle following the work by Pinyol et al. (2007). In this way, dissociation of MH can be assessed on the basis of the stress state and temperature prevailing locally within the hydrate component. Besides, its structuring effect is naturally accounted for by the model according to patterns of MH inclusions within soil pores. This paper describes the fundamental hypothesis behind the model and its formulation. Its performance is assessed by comparison with laboratory data presented in the literature. An analysis of MHBS response to several stress-temperature paths representing potential field cases is finally presented. References

  9. MATHEMATICAL MODEL OF OSCILLATIONS OF BEARING BODY FRAME OF EMERGENCY AND REPAIR RAILCARS

    Directory of Open Access Journals (Sweden)

    Galina KHROMOVA

    2017-04-01

    Full Text Available Nowadays, the importance of maintenance and effective use of available railcars in the railway transport is growing, and researchers and technical experts are working to address this issue with the use of various techniques. The authors address the use of analytical technique, which includes mathematical solutions for flexural and longitudinal fluctuations of the bearing framework of a railcar body frame. The calculation is performed in connection with the modernization of the body frame of emergency and repair rail service car, taking into account the variability in section, mass, longitudinal stiffness, and bending stiffness. It allows for extension of the useful life of their operation, with special focus on vehicles owned by Joint-Stock Company "Uzbekistan Railways". The simulation of equivalent bearing body frame of emergency and repair rail service car was carried out using an elastic rod with variable parameters including stiffness and mass. The difference between the proposed model and the existing ones is due to the variability in cross section, mass, and the longitudinal and bending stiffness along the length of equivalent beam, which corresponds to the actual conditions of operation and data of the experimental studies conducted by the authors on the bearing frames of electric locomotives’ variable sections. The frequency analysis that was carried out with the use of the Mathcad 14 programming showed that the frequencies of natural oscillations change on n harmonicas = 1, 2, 3 … 5. As regards longitudinal oscillations of system, in case of introduction of the damping subfloor, the frequency of natural oscillations of the upgraded rail car frame λ1mn increases on comparing with standard λ1n (for example, in case of n = 5 the frequency is 0.587 and 0.602 Hz/m, respectively.

  10. Finding all BRCA pathogenic mutation carriers : best practice models

    NARCIS (Netherlands)

    Hoogerbrugge, Nicoline; Jongmans, Marjolijn CJ

    Identifying germline BRCA pathogenic mutations in patients with ovarian or breast cancer is a crucial component in the medical management of affected patients. Furthermore, the relatives of affected patients can be offered genetic testing. Relatives who test positive for a germline BRCA pathogenic

  11. Finding all BRCA pathogenic mutation carriers: best practice models

    NARCIS (Netherlands)

    Hoogerbrugge, N.; Jongmans, M.C.

    2016-01-01

    Identifying germline BRCA pathogenic mutations in patients with ovarian or breast cancer is a crucial component in the medical management of affected patients. Furthermore, the relatives of affected patients can be offered genetic testing. Relatives who test positive for a germline BRCA pathogenic

  12. Mutation-selection dynamics and error threshold in an evolutionary model for Turing machines.

    Science.gov (United States)

    Musso, Fabio; Feverati, Giovanni

    2012-01-01

    We investigate the mutation-selection dynamics for an evolutionary computation model based on Turing machines. The use of Turing machines allows for very simple mechanisms of code growth and code activation/inactivation through point mutations. To any value of the point mutation probability corresponds a maximum amount of active code that can be maintained by selection and the Turing machines that reach it are said to be at the error threshold. Simulations with our model show that the Turing machines population evolve toward the error threshold. Mathematical descriptions of the model point out that this behaviour is due more to the mutation-selection dynamics than to the intrinsic nature of the Turing machines. This indicates that this result is much more general than the model considered here and could play a role also in biological evolution. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Modelling of saturated soil slopes equilibrium with an account of the liquid phase bearing capacity

    Directory of Open Access Journals (Sweden)

    Maltseva Tatyana

    2017-01-01

    Full Text Available The paper presents an original method of solving the problem of uniformly distributed load action on a two-phase elastic half-plane with the use of a kinematic model. The kinematic model (Maltsev L.E. of two-phase medium is based on two new hypotheses according to which the stress and strain state of the two-phase body is described by a system of linear elliptic equations. These equations differ from the Lame equations of elasticity theory with two terms in each equation. The terms describe the bearing capacity of the liquid phase or a decrease in stress in the solid phase. The finite element method has been chosen as a solution method.

  14. Regression Models for the Bearing Capacity of Crude Oil Contaminated Soils in Ekakpamre and Kwale, Niger Delta, Nigeria.

    Directory of Open Access Journals (Sweden)

    2016-11-01

    Full Text Available The Niger Delta Region of Nigeria has suffered severe environmental pollution due to ever increasing oil exploration and exploitation activities in the region making the communities highly vulnerable to the effects of oil spill and other associated environmental degradation. Using eight soil samples collected from two oil-rich communities in two Local Government Areas of Delta State, the effects of oil spill on the load bearing properties of the soils were examined and used to develop regression models for the bearing capacity (for strip foundation footing of oil contaminated soils. The triaxial test showed the mean values of the bearing capacity of the uncontaminated soil samples (which served as control as 170.718 KN/m2 and 601.49KN/m2 . The samples were then thoroughly mixed with crude oil(to simulate the site conditions at 5%, 10%, 15%, and 20%. The result of the triaxial test showed that oil reduces the bearing capacity of the soil and as the percentage increased to 20% oil, the bearing capacity dropped to 56.60KN/m2 and 61.50 KN/m2 respectively for the two study locations. Regression models were then developed to estimate the bearing capacity of the oil contaminated soils at any level of contamination in the study locations.

  15. Coupled numerical modeling of gas hydrates bearing sediments from laboratory to field-scale conditions

    Science.gov (United States)

    Sanchez, M. J.; Santamarina, C.; Gai, X., Sr.; Teymouri, M., Sr.

    2017-12-01

    Stability and behavior of Hydrate Bearing Sediments (HBS) are characterized by the metastable character of the gas hydrate structure which strongly depends on thermo-hydro-chemo-mechanical (THCM) actions. Hydrate formation, dissociation and methane production from hydrate bearing sediments are coupled THCM processes that involve, amongst other, exothermic formation and endothermic dissociation of hydrate and ice phases, mixed fluid flow and large changes in fluid pressure. The analysis of available data from past field and laboratory experiments, and the optimization of future field production studies require a formal and robust numerical framework able to capture the very complex behavior of this type of soil. A comprehensive fully coupled THCM formulation has been developed and implemented into a finite element code to tackle problems involving gas hydrates sediments. Special attention is paid to the geomechanical behavior of HBS, and particularly to their response upon hydrate dissociation under loading. The numerical framework has been validated against recent experiments conducted under controlled conditions in the laboratory that challenge the proposed approach and highlight the complex interaction among THCM processes in HBS. The performance of the models in these case studies is highly satisfactory. Finally, the numerical code is applied to analyze the behavior of gas hydrate soils under field-scale conditions exploring different features of material behavior under possible reservoir conditions.

  16. Modeling multi-scale resource selection for bear rub trees in northwestern Montana

    Science.gov (United States)

    Morgan Henderson, Matthew J.; Hebblewhite, Mark; Mitchell, Michael S.; Stetz, Jeffrey B.; Kendall, Katherine C.; Carlson, Ross T.

    2015-01-01

    Both black (Ursus americanus) and grizzly bears (U. arctos) are known to rub on trees and other objects, producing a network of repeatedly used and identifiable rub sites. In 2012, we used a resource selection function to evaluate hypothesized relationships between locations of 887 bear rubs in northwestern Montana, USA, and elevation, slope angle, density of open roads and distance from areas of heightened plant-productivity likely containing forage for bears. Slope and density of open roads were negatively correlated with rub presence. No other covariates were supported as explanatory variables. We also hypothesized that bear rubs would be more strongly associated with closed roads and developed trails than with game trails. The frequencies of bear rubs on 30 paired segments of developed tracks and game trails were not different. Our results suggest bear rubs may be associated with bear travel routes, and support their use as “random” sampling devices for non-invasive spatial capture–recapture population monitoring.

  17. Enhanced susceptibility of a transposable-element-bearing strain of Drosophila melanogaster to somatic eye-color mutations by ethyl nitrosourea, methyl nitrosourea, and X-rays

    International Nuclear Information System (INIS)

    Ryo, H.; Kondo, S.; Rasmuson, B.

    1983-01-01

    A strain of Drosophila with the genes z and w + plus a transposable element (TE) is about 3 times more sensitive than a strain without TE toward somatic eye-color mutations after larval exposure to ethyl nitrosourea, methyl nitrosourea and X-rays. The assay system with TE is simple, reliable, and sensitive for detecting somatic mutations induced in vivo by mutagens. (orig.)

  18. Precambrian uranium-bearing quartz-pebble conglomerates: exploration model and United States resource potential

    Energy Technology Data Exchange (ETDEWEB)

    Houston, R.S.; Karlstrom, K.E.

    1979-11-01

    Uranium has been discovered in fluvial quartz-pebble conglomerates in most of the Precambrian shield areas of the world, including the Canadian, African, South American, Indian, Baltic, and Australian shields. Occurrences in these and other areas are shown. Two of these occurrences, the Huronian supergroup of Canada and the Witwatersrand deposit of South Africa contain 20 to 30 percent of the planet's known uranium reserves. Thus it is critical that we understand the origin of these deposits and develop exploration models that can aid in finding new deposits. Inasmuch as these uranium-bearing conglomerates are confined almost entirely to rocks of Precambrian age, Part I of this review begins with a discussion of Precambrian geology as it applies to the conglomerates. This is followed by a discussion of genetic concepts, a discussion of unresolved problems, and finally a suggested exploration model. Part II summarizes known and potential occurrences of Precambrian fossil placers in the world and evaluates them in terms of the suggested exploration model. Part III discusses the potential for important Precambrian fossil-placer uranium deposits in the United States and includes suggestions that may be helpful in establishing an exploration program in this country. Part III also brings together new (1975-1978) data on uranium occurrences in the Precambrian of the Wyoming Province. Part IV is a complete bibliography of Precambrian fossil placers, divided according to geographical areas. In total, this paper is designed to be a comprehensive review of Precambrian uranium-bearing fossil placers which will be of use to uranium explorationists and to students of Precambrian geology.

  19. Precambrian uranium-bearing quartz-pebble conglomerates: exploration model and United States resource potential

    International Nuclear Information System (INIS)

    Houston, R.S.; Karlstrom, K.E.

    1979-11-01

    Uranium has been discovered in fluvial quartz-pebble conglomerates in most of the Precambrian shield areas of the world, including the Canadian, African, South American, Indian, Baltic, and Australian shields. Occurrences in these and other areas are shown. Two of these occurrences, the Huronian supergroup of Canada and the Witwatersrand deposit of South Africa contain 20 to 30 percent of the planet's known uranium reserves. Thus it is critical that we understand the origin of these deposits and develop exploration models that can aid in finding new deposits. Inasmuch as these uranium-bearing conglomerates are confined almost entirely to rocks of Precambrian age, Part I of this review begins with a discussion of Precambrian geology as it applies to the conglomerates. This is followed by a discussion of genetic concepts, a discussion of unresolved problems, and finally a suggested exploration model. Part II summarizes known and potential occurrences of Precambrian fossil placers in the world and evaluates them in terms of the suggested exploration model. Part III discusses the potential for important Precambrian fossil-placer uranium deposits in the United States and includes suggestions that may be helpful in establishing an exploration program in this country. Part III also brings together new (1975-1978) data on uranium occurrences in the Precambrian of the Wyoming Province. Part IV is a complete bibliography of Precambrian fossil placers, divided according to geographical areas. In total, this paper is designed to be a comprehensive review of Precambrian uranium-bearing fossil placers which will be of use to uranium explorationists and to students of Precambrian geology

  20. Wayside Bearing Fault Diagnosis Based on a Data-Driven Doppler Effect Eliminator and Transient Model Analysis

    Science.gov (United States)

    Liu, Fang; Shen, Changqing; He, Qingbo; Zhang, Ao; Liu, Yongbin; Kong, Fanrang

    2014-01-01

    A fault diagnosis strategy based on the wayside acoustic monitoring technique is investigated for locomotive bearing fault diagnosis. Inspired by the transient modeling analysis method based on correlation filtering analysis, a so-called Parametric-Mother-Doppler-Wavelet (PMDW) is constructed with six parameters, including a center characteristic frequency and five kinematic model parameters. A Doppler effect eliminator containing a PMDW generator, a correlation filtering analysis module, and a signal resampler is invented to eliminate the Doppler effect embedded in the acoustic signal of the recorded bearing. Through the Doppler effect eliminator, the five kinematic model parameters can be identified based on the signal itself. Then, the signal resampler is applied to eliminate the Doppler effect using the identified parameters. With the ability to detect early bearing faults, the transient model analysis method is employed to detect localized bearing faults after the embedded Doppler effect is eliminated. The effectiveness of the proposed fault diagnosis strategy is verified via simulation studies and applications to diagnose locomotive roller bearing defects. PMID:24803197

  1. Nonlinear dynamic model of a gear-rotor-bearing system considering the flash temperature

    Science.gov (United States)

    Gou, Xiangfeng; Zhu, Lingyun; Qi, Changjun

    2017-12-01

    The instantaneous flash temperature is an important factor for gears in service. To investigate the effect of the flash temperature of a tooth surface on the dynamics of the spur gear system, a modified nonlinear dynamic model of a gear-rotor-bearing system is established. The factors such as the contact temperature of the tooth surface, time-varying stiffness, tooth surface friction, backlash, the comprehensive transmission error and so on are considered. The flash temperature of a tooth surface of pinion and gear is formulated according to Blok's flash temperature theory. The mathematical expression of the contact temperature of the tooth surface varied with time is derived and the tooth profile deformation caused by the change of the flash temperature of the tooth surface is calculated. The expression of the mesh stiffness varied with the flash temperature of the tooth surface is derived based on Hertz contact theory. The temperature stiffness is proposed and added to the nonlinear dynamic model of the system. The influence of load on the flash temperature of the tooth surface is analyzed in the parameters plane. The variation of the flash temperature of the tooth surface is studied. The numerical results indicate that the calculated method of the flash temperature of the gear tooth surface is effective and it can reflect the rules for the change of gear meshing temperature and sliding of the gear tooth surface. The effects of frequency, backlash, bearing clearance, comprehensive transmission error and time-varying stiffness on the nonlinear dynamics of the system are analyzed according to the bifurcation diagrams, Top Lyapunov Exponent (TLE) spectrums, phase portraits and Poincaré maps. Some nonlinear phenomena such as periodic bifurcation, grazing bifurcation, quasi-periodic bifurcation, chaos and its routes to chaos are investigated and the critical parameters are identified. The results provide an understanding of the system and serve as a useful reference

  2. Active lubrication applied to radial gas journal bearings. Part 1: Modeling

    DEFF Research Database (Denmark)

    Morosi, Stefano; Santos, Ilmar

    2011-01-01

    Active bearings represent a mechatronic answer to the growing industrial need to high performance turbomachinery. The present contribution aims at demonstrate the feasibility of applying active lubrication to gas journal bearings. The principle of operation is to generate active forces by regulat......Active bearings represent a mechatronic answer to the growing industrial need to high performance turbomachinery. The present contribution aims at demonstrate the feasibility of applying active lubrication to gas journal bearings. The principle of operation is to generate active forces...... by regulating radial injection of lubricant through the means of piezoelectric actuators mounted on the back of the bearing sleeves. A feedback law is used to couple the dynamic of a simplified rotor-bearing system with the pneumatic and dynamic characteristics of a piezoelectric actuated valve system. Selected...

  3. An analysis of heat conduction in polar bear hairs using one-dimensional fractional model

    Directory of Open Access Journals (Sweden)

    Zhu Wei-Hong

    2016-01-01

    Full Text Available Hairs of a polar bear are of superior properties such as the excellent thermal protection. The polar bears can perennially live in an extremely cold environment and can maintain body temperature at around 37 °C. Why do polar bears can resist such cold environment? Its membrane-pore structure plays an important role. In the previous work, we established a 1-D fractional heat conduction equation to reveal the hidden mechanism for the hairs. In this paper, we further discuss solutions and parameters of the equation established and analyze heat conduction in polar bear hairs.

  4. Thermodynamic modelling of Cr-bearing garnets with implications for diamond inclusions and peridotite xenoliths

    Science.gov (United States)

    Klemme, S.; Ivanic, T. J.; Connolly, J. A. D.; Harte, B.

    2009-11-01

    A new approach is presented for modelling Cr-rich peridotite compositions and garnet-spinel compositions found in diamonds and xenoliths at conditions relevant to the deep continental Earth. Using recent experimental data, it is now possible to calculate phase relations and mineral compositions relevant to pressures, temperatures, and compositions of the deep lithospheric Earth using free energy minimization techniques. Here we present calculated phase relations in Cr-rich mantle compositions from pressures of 20-60 kbar, and temperatures 800-1400 °C. The model is successful at modelling a wide range of natural mineral compositions which are found as xenoliths in diamond-bearing kimberlites from South Africa, and is illustrated using suites of Cr-rich xenoliths from near Kimberley, South Africa. The model can explain and quantify instances of garnet zonation in naturally occurring mantle rocks as a consequence of pressure-temperature re-equilibration; and shows that not all garnet zonations result from metasomatic processes. This sheds further light on peridotitic diamond inclusions and their abundances, and allows further quantitative constraints to be applied to diamond-indicator mineral chemistry.

  5. Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries

    International Nuclear Information System (INIS)

    Monteiro Santos, Erika Maria; Silva Junior, Wilson Araujo da; Carraro, Dirce Maria; Rossi, Benedito Mauro; Valentin, Mev Dominguez; Carneiro, Felipe; Oliveira, Ligia Petrolini de; Oliveira Ferreira, Fabio de; Junior, Samuel Aguiar; Nakagawa, Wilson Toshihiko; Gomy, Israel; Faria Ferraz, Victor Evangelista de

    2012-01-01

    Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome. Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed. Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of ≥ 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson). The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models

  6. Which melanoma patient carries a BRAF-mutation? A comparison of predictive models.

    Science.gov (United States)

    Eigentler, Thomas; Assi, Zeinab; Hassel, Jessica C; Heinzerling, Lucie; Starz, Hans; Berneburg, Mark; Bauer, Jürgen; Garbe, Claus

    2016-06-14

    In patients with advanced melanoma the detection of BRAF mutations is considered mandatory before the initiation of an expensive treatment with BRAF/MEK inhibitors. Sometimes it is difficult to perform such an analysis if archival tumor tissue is not available and fresh tissue has to be collected. 514 of 1170 patients (44%) carried a BRAF mutation. All models revealed age and histological subtype of melanoma as the two major predictive variables. Accuracy ranged from 0.65-0.71, being best in the random forest model. Sensitivity ranged 0.76-0.84, again best in the random forest model. Specificity was low in all models ranging 0.51-0.55. We collected the clinical data and mutational status of 1170 patients with advanced melanoma and established three different predictive models (binary logistic regression, classification and regression trees, and random forest) to forecast the BRAF status. Up to date statistical models are not able to predict BRAF mutations in an acceptable accuracy. The analysis of the mutational status by sequencing or immunohistochemistry must still be considered as standard of care.

  7. Structure Based Thermostability Prediction Models for Protein Single Point Mutations with Machine Learning Tools.

    Directory of Open Access Journals (Sweden)

    Lei Jia

    Full Text Available Thermostability issue of protein point mutations is a common occurrence in protein engineering. An application which predicts the thermostability of mutants can be helpful for guiding decision making process in protein design via mutagenesis. An in silico point mutation scanning method is frequently used to find "hot spots" in proteins for focused mutagenesis. ProTherm (http://gibk26.bio.kyutech.ac.jp/jouhou/Protherm/protherm.html is a public database that consists of thousands of protein mutants' experimentally measured thermostability. Two data sets based on two differently measured thermostability properties of protein single point mutations, namely the unfolding free energy change (ddG and melting temperature change (dTm were obtained from this database. Folding free energy change calculation from Rosetta, structural information of the point mutations as well as amino acid physical properties were obtained for building thermostability prediction models with informatics modeling tools. Five supervised machine learning methods (support vector machine, random forests, artificial neural network, naïve Bayes classifier, K nearest neighbor and partial least squares regression are used for building the prediction models. Binary and ternary classifications as well as regression models were built and evaluated. Data set redundancy and balancing, the reverse mutations technique, feature selection, and comparison to other published methods were discussed. Rosetta calculated folding free energy change ranked as the most influential features in all prediction models. Other descriptors also made significant contributions to increasing the accuracy of the prediction models.

  8. Multivariate model of female black bear habitat use for a Geographic Information System

    Science.gov (United States)

    Clark, Joseph D.; Dunn, James E.; Smith, Kimberly G.

    1993-01-01

    Simple univariate statistical techniques may not adequately assess the multidimensional nature of habitats used by wildlife. Thus, we developed a multivariate method to model habitat-use potential using a set of female black bear (Ursus americanus) radio locations and habitat data consisting of forest cover type, elevation, slope, aspect, distance to roads, distance to streams, and forest cover type diversity score in the Ozark Mountains of Arkansas. The model is based on the Mahalanobis distance statistic coupled with Geographic Information System (GIS) technology. That statistic is a measure of dissimilarity and represents a standardized squared distance between a set of sample variates and an ideal based on the mean of variates associated with animal observations. Calculations were made with the GIS to produce a map containing Mahalanobis distance values within each cell on a 60- × 60-m grid. The model identified areas of high habitat use potential that could not otherwise be identified by independent perusal of any single map layer. This technique avoids many pitfalls that commonly affect typical multivariate analyses of habitat use and is a useful tool for habitat manipulation or mitigation to favor terrestrial vertebrates that use habitats on a landscape scale.

  9. The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish models.

    Science.gov (United States)

    Yen, Jennifer; White, Richard M; Wedge, David C; Van Loo, Peter; de Ridder, Jeroen; Capper, Amy; Richardson, Jennifer; Jones, David; Raine, Keiran; Watson, Ian R; Wu, Chang-Jiun; Cheng, Jiqiu; Martincorena, Iñigo; Nik-Zainal, Serena; Mudie, Laura; Moreau, Yves; Marshall, John; Ramakrishna, Manasa; Tarpey, Patrick; Shlien, Adam; Whitmore, Ian; Gamble, Steve; Latimer, Calli; Langdon, Erin; Kaufman, Charles; Dovey, Mike; Taylor, Alison; Menzies, Andy; McLaren, Stuart; O'Meara, Sarah; Butler, Adam; Teague, Jon; Lister, James; Chin, Lynda; Campbell, Peter; Adams, David J; Zon, Leonard I; Patton, E Elizabeth; Stemple, Derek L; Futreal, P Andy

    2013-01-01

    Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process. To decipher the genetics of these melanomas, we sequence the protein coding exons of 53 primary melanomas generated from several BRAF(V600E) or NRAS(Q61K) driven transgenic zebrafish lines. We find that engineered zebrafish melanomas show an overall low mutation burden, which has a strong, inverse association with the number of initiating germline drivers. Although tumors reveal distinct mutation spectrums, they show mostly C > T transitions without UV light exposure, and enrichment of mutations in melanogenesis, p53 and MAPK signaling. Importantly, a recurrent amplification occurring with pre-configured drivers BRAF(V600E) and p53-/- suggests a novel path of BRAF cooperativity through the protein kinase A pathway. This is the first analysis of a melanoma mutational landscape in the absence of UV light, where tumors manifest with remarkably low mutation burden and high heterogeneity. Genotype specific amplification of protein kinase A in cooperation with BRAF and p53 mutation suggests the involvement of melanogenesis in these tumors. This work is important for defining the spectrum of events in BRAF or NRAS driven melanoma in the absence of UV light, and for informed exploitation of models such as transgenic zebrafish to better understand mechanisms leading to human melanoma formation.

  10. SVM classification model in depression recognition based on mutation PSO parameter optimization

    Directory of Open Access Journals (Sweden)

    Zhang Ming

    2017-01-01

    Full Text Available At present, the clinical diagnosis of depression is mainly through structured interviews by psychiatrists, which is lack of objective diagnostic methods, so it causes the higher rate of misdiagnosis. In this paper, a method of depression recognition based on SVM and particle swarm optimization algorithm mutation is proposed. To address on the problem that particle swarm optimization (PSO algorithm easily trap in local optima, we propose a feedback mutation PSO algorithm (FBPSO to balance the local search and global exploration ability, so that the parameters of the classification model is optimal. We compared different PSO mutation algorithms about classification accuracy for depression, and found the classification accuracy of support vector machine (SVM classifier based on feedback mutation PSO algorithm is the highest. Our study promotes important reference value for establishing auxiliary diagnostic used in depression recognition of clinical diagnosis.

  11. Mutational effects and population dynamics during viral adaptation challenge current models.

    Science.gov (United States)

    Miller, Craig R; Joyce, Paul; Wichman, Holly A

    2011-01-01

    Adaptation in haploid organisms has been extensively modeled but little tested. Using a microvirid bacteriophage (ID11), we conducted serial passage adaptations at two bottleneck sizes (10(4) and 10(6)), followed by fitness assays and whole-genome sequencing of 631 individual isolates. Extensive genetic variation was observed including 22 beneficial, several nearly neutral, and several deleterious mutations. In the three large bottleneck lines, up to eight different haplotypes were observed in samples of 23 genomes from the final time point. The small bottleneck lines were less diverse. The small bottleneck lines appeared to operate near the transition between isolated selective sweeps and conditions of complex dynamics (e.g., clonal interference). The large bottleneck lines exhibited extensive interference and less stochasticity, with multiple beneficial mutations establishing on a variety of backgrounds. Several leapfrog events occurred. The distribution of first-step adaptive mutations differed significantly from the distribution of second-steps, and a surprisingly large number of second-step beneficial mutations were observed on a highly fit first-step background. Furthermore, few first-step mutations appeared as second-steps and second-steps had substantially smaller selection coefficients. Collectively, the results indicate that the fitness landscape falls between the extremes of smooth and fully uncorrelated, violating the assumptions of many current mutational landscape models.

  12. Laser-optical and numerical Research of the flow inside the lubricating gap of a journal bearing model

    Directory of Open Access Journals (Sweden)

    Riedel M.

    2013-04-01

    Full Text Available The laser-optical research of the flow inside the lubricating gap of a journal bearing model is one important task in a larger overall project. The long-term objective is the development of an easy-to-work calculation tool which delivers information about the causes and consequences of cavitation processes in hydrodynamically lubricated journal bearings. Hence, it will be possible to find statements for advantageous and disadvantageous geometrical shapes of the bushings. In conclusion such a calculation tool can provide important insights for the construction and design of future journal bearings. Current design programs are based on a two-dimensional approach for the lubricating gap. The first dimension is the breath of the bearing and the second dimension is the circumferential direction of the bearing. The third dimension, the expansion of the gap in radial direction, will be neglected. Instead of an exact resolution of the flow pattern inside the gap, turbulence models are in use. Past studies on numerical and experimental field have shown that inside the lubricating gap clearly organized and predominantly laminar flow structures can be found. Thus, for a detailed analysis of the reasons and effects of cavitation bubbles, a three-dimensional resolution of the lubricating gap is inevitable. In addition to the qualitative evaluation of the flow with visualization experiments it is possible to perform angle-based velocity measurements inside the gap with the help of a triggered Laser-Doppler- Velocimeter (LDV. The results of these measurements are used to validate three-dimensional CFD flow simulations, and to optimize the numerical mesh structure and the boundary conditions. This paper will present the experimental setup of the bearing model, some exemplary results of the visualization experiments and LDV measurements as well as a comparison between experimental and numerical results.

  13. Laser-optical and numerical Research of the flow inside the lubricating gap of a journal bearing model

    Science.gov (United States)

    Nobis, M.; Stücke, P.; Schmidt, M.; Riedel, M.

    2013-04-01

    The laser-optical research of the flow inside the lubricating gap of a journal bearing model is one important task in a larger overall project. The long-term objective is the development of an easy-to-work calculation tool which delivers information about the causes and consequences of cavitation processes in hydrodynamically lubricated journal bearings. Hence, it will be possible to find statements for advantageous and disadvantageous geometrical shapes of the bushings. In conclusion such a calculation tool can provide important insights for the construction and design of future journal bearings. Current design programs are based on a two-dimensional approach for the lubricating gap. The first dimension is the breath of the bearing and the second dimension is the circumferential direction of the bearing. The third dimension, the expansion of the gap in radial direction, will be neglected. Instead of an exact resolution of the flow pattern inside the gap, turbulence models are in use. Past studies on numerical and experimental field have shown that inside the lubricating gap clearly organized and predominantly laminar flow structures can be found. Thus, for a detailed analysis of the reasons and effects of cavitation bubbles, a three-dimensional resolution of the lubricating gap is inevitable. In addition to the qualitative evaluation of the flow with visualization experiments it is possible to perform angle-based velocity measurements inside the gap with the help of a triggered Laser-Doppler- Velocimeter (LDV). The results of these measurements are used to validate three-dimensional CFD flow simulations, and to optimize the numerical mesh structure and the boundary conditions. This paper will present the experimental setup of the bearing model, some exemplary results of the visualization experiments and LDV measurements as well as a comparison between experimental and numerical results.

  14. Structure modeling and mutational analysis of gap junction beta 2 ...

    African Journals Online (AJOL)

    Therefore, a 3D structure of GJB2 was developed using comparative modeling approach. For modeling, a template was selected by blastp at NCBI and the best template selected was 2ZW3. By comparing the template-target sequence, a model was created using MODELLER, a program for homology modeling.

  15. THE MODEL OF THE RADIAL-THRUST BALL BEARING FOR ANALYSIS OF NONLINEAR VIBRATIONS OF THE ROTOR

    Directory of Open Access Journals (Sweden)

    S. Filipkovskyi

    2015-12-01

    Full Text Available The non-linear model of resilient forces of pre-loaded ball bearing is developed. The contact forces are obtained and arranged in the Heyn’s row on the basis of Herts theory. The obtained model is used for solving the problem of non-linear dynamics of vehicles. The design samples correspond to calculations performed with the help of the traditional model.

  16. A Mathematical Model of Prostate Tumor Growth Under Hormone Therapy with Mutation Inhibitor

    Science.gov (United States)

    Tao, Youshan; Guo, Qian; Aihara, Kazuyuki

    2010-04-01

    This paper extends Jackson’s model describing the growth of a prostate tumor with hormone therapy to a new one with hypothetical mutation inhibitors. The new model not only considers the mutation by which androgen-dependent (AD) tumor cells mutate into androgen-independent (AI) ones but also introduces inhibition which is assumed to change the mutation rate. The tumor consists of two types of cells (AD and AI) whose proliferation and apoptosis rates are functions of androgen concentration. The mathematical model represents a free-boundary problem for a nonlinear system of parabolic equations, which describe the evolution of the populations of the above two types of tumor cells. The tumor surface is a free boundary, whose velocity is equal to the cell’s velocity there. Global existence and uniqueness of solutions of this model is proved. Furthermore, explicit formulae of tumor volume at any time t are found in androgen-deprived environment under the assumption of radial symmetry, and therefore the dynamics of tumor growth under androgen-deprived therapy could be predicted by these formulae. Qualitative analysis and numerical simulation show that controlling the mutation may improve the effect of hormone therapy or delay a tumor relapse.

  17. Snow and ice on Bear Lake (Alaska – sensitivity experiments with two lake ice models

    Directory of Open Access Journals (Sweden)

    Tido Semmler

    2012-03-01

    Full Text Available Snow and ice thermodynamics of Bear Lake (Alaska are investigated with a simple freshwater lake model (FLake and a more complex snow and ice thermodynamic model (HIGHTSI. A number of sensitivity experiments have been carried out to investigate the influence of snow and ice parameters and of different complexity on the results. Simulation results are compared with observations from the Alaska Lake Ice and Snow Observatory Network. Adaptations of snow thermal and optical properties in FLake can largely improve accuracy of the results. Snow-to-ice transformation is important for HIGHTSI to calculate the total ice mass balance. The seasonal maximum ice depth is simulated in FLake with a bias of −0.04 m and in HIGHTSI with no bias. Correlation coefficients between ice depth measurements and simulations are high (0.74 for FLake and 0.9 for HIGHTSI. The snow depth simulation can be improved by taking into account a variable snow density. Correlation coefficients for surface temperature are 0.72 for FLake and 0.81 for HIGHTSI. Overall, HIGHTSI gives slightly more accurate surface temperature than FLake probably due to the consideration of multiple snow and ice layers and the expensive iteration calculation procedure.

  18. A numerical test method of California bearing ratio on graded crushed rocks using particle flow modeling

    Directory of Open Access Journals (Sweden)

    Yingjun Jiang

    2015-04-01

    Full Text Available In order to better understand the mechanical properties of graded crushed rocks (GCRs and to optimize the relevant design, a numerical test method based on the particle flow modeling technique PFC2D is developed for the California bearing ratio (CBR test on GCRs. The effects of different testing conditions and micro-mechanical parameters used in the model on the CBR numerical results have been systematically studied. The reliability of the numerical technique is verified. The numerical results suggest that the influences of the loading rate and Poisson's ratio on the CBR numerical test results are not significant. As such, a loading rate of 1.0–3.0 mm/min, a piston diameter of 5 cm, a specimen height of 15 cm and a specimen diameter of 15 cm are adopted for the CBR numerical test. The numerical results reveal that the CBR values increase with the friction coefficient at the contact and shear modulus of the rocks, while the influence of Poisson's ratio on the CBR values is insignificant. The close agreement between the CBR numerical results and experimental results suggests that the numerical simulation of the CBR values is promising to help assess the mechanical properties of GCRs and to optimize the grading design. Besides, the numerical study can provide useful insights on the mesoscopic mechanism.

  19. Process Options Description for Vitrification Flowsheet Model of INEEL Sodium Bearing Waste

    International Nuclear Information System (INIS)

    Nichols, T.T.; Taylor, D.D.; Lauerhass, L.; Barnes, C.M.

    2002-01-01

    The technical information required for the development of a basic steady-state process simulation of the vitrification treatment train of sodium bearing waste (SBW) at Idaho National Engineering and Environmental Laboratory (INEEL) is presented. The objective of the modeling effort is to provide the predictive capability required to optimize an entire treatment train and assess system-wide impacts of local changes at individual unit operations, with the aim of reducing the schedule and cost of future process/facility design efforts. All the information required a priori for engineers to construct and link unit operation modules in a commercial software simulator to represent the alternative treatment trains is presented. The information is of a mid- to high-level nature and consists of the following: (1) a description of twenty-four specific unit operations--their operating conditions and constraints, primary species and key outputs, and the initial modeling approaches that will be used in the first year of the simulation's development; (2) three potential configurations of the unit operations (trains) and their interdependencies via stream connections; and (3) representative stream compositional makeups

  20. Properties and modeling of GWAS when complex disease risk is due to non-complementing, deleterious mutations in genes of large effect.

    Directory of Open Access Journals (Sweden)

    Kevin R Thornton

    Full Text Available Current genome-wide association studies (GWAS have high power to detect intermediate frequency SNPs making modest contributions to complex disease, but they are underpowered to detect rare alleles of large effect (RALE. This has led to speculation that the bulk of variation for most complex diseases is due to RALE. One concern with existing models of RALE is that they do not make explicit assumptions about the evolution of a phenotype and its molecular basis. Rather, much of the existing literature relies on arbitrary mapping of phenotypes onto genotypes obtained either from standard population-genetic simulation tools or from non-genetic models. We introduce a novel simulation of a 100-kilobase gene region, based on the standard definition of a gene, in which mutations are unconditionally deleterious, are continuously arising, have partially recessive and non-complementing effects on phenotype (analogous to what is widely observed for most Mendelian disorders, and are interspersed with neutral markers that can be genotyped. Genes evolving according to this model exhibit a characteristic GWAS signature consisting of an excess of marginally significant markers. Existing tests for an excess burden of rare alleles in cases have low power while a simple new statistic has high power to identify disease genes evolving under our model. The structure of linkage disequilibrium between causative mutations and significantly associated markers under our model differs fundamentally from that seen when rare causative markers are assumed to be neutral. Rather than tagging single haplotypes bearing a large number of rare causative alleles, we find that significant SNPs in a GWAS tend to tag single causative mutations of small effect relative to other mutations in the same gene. Our results emphasize the importance of evaluating the power to detect associations under models that are genetically and evolutionarily motivated.

  1. Reduced-order modeling for rotating rotor-bearing systems with cracked impellers using three-dimensional finite element models

    Science.gov (United States)

    Wang, Shuai; Wang, Yu; Zi, Yanyang; Li, Bing; He, Zhengjia

    2015-10-01

    A novel reduced-order modeling method is presented in this paper for dynamics analysis of rotating impeller-shaft-bearing assembly with cracked impellers. Based on three-dimensional finite element model, the complex component mode synthesis (CMS) method is employed to generate an efficient reduced-order model (ROM) for studying the effects of crack on the global vibration of the rotating assembly. First, a modeling framework for impeller-shaft-bearing systems in rotating frame is presented. Rotational effects, including Coriolis matrix and centrifugal softening, have been taken into account. Then, the governing equation of motion of the damped gyroscopic system is reduced by the complex CMS method. Finally, the obtained ROM is employed to study the effects of crack on assembly's vibration. During the steady-state response analysis, external excitations on the impeller due to rotor-stator interactions have been taken into account, which was however neglected in previous investigations on rotordynamics. Numerical results show that the lower-order eigenvalues and the unbalance response of the assembly are not sensitive to the local crack on impeller. Nevertheless, the flexible coupling between impeller and shaft becomes more complex when the air flow-induced excitations are considered. Under EO1 traveling wave excitations, a crack leads to slight changes in the assembly's response. In contrast, the effect of crack becomes significant when the assembly is excited by EO2 and higher EO excitations. Moreover, the nonlinear crack breathing effects affect the assembly's response obviously. Finally, a potential technique for detecting the crack on impeller during operation is discussed.

  2. Disheveled hair and ear (Dhe, a spontaneous mouse Lmna mutation modeling human laminopathies.

    Directory of Open Access Journals (Sweden)

    Paul R Odgren

    Full Text Available BACKGROUND: Investigations of naturally-occurring mutations in animal models provide important insights and valuable disease models. Lamins A and C, along with lamin B, are type V intermediate filament proteins which constitute the proteinaceous boundary of the nucleus. LMNA mutations in humans cause a wide range of phenotypes, collectively termed laminopathies. To identify the mutation and investigate the phenotype of a spontaneous, semi-dominant mutation that we have named Disheveled hair and ear (Dhe, which causes a sparse coat and small external ears in heterozygotes and lethality in homozygotes by postnatal day 10. FINDINGS: Genetic mapping identified a point mutation in the Lmna gene, causing a single amino acid change, L52R, in the coiled coil rod domain of lamin A and C proteins. Cranial sutures in Dhe/+ mice failed to close. Gene expression for collagen types I and III in sutures was deficient. Skulls were small and disproportionate. Skeletons of Dhe/+ mice were hypomineralized and total body fat was deficient in males. In homozygotes, skin and oral mucosae were dysplastic and ulcerated. Nuclear morphometry of cultured cells revealed gene dose-dependent blebbing and wrinkling. CONCLUSION: Dhe mice should provide a useful new model for investigations of the pathogenesis of laminopathies.

  3. Magnetic Bearing

    OpenAIRE

    Anbuselvan. T; Vinothkumar. K; Sai Vikash. M

    2013-01-01

    The use of bearings is essential to all types of machines, especially in marine aspects they provide the function of supporting heavier component in a desired position. These bearings have contact with the rotating part and causes surface wear which can be controlled by lubrication. Researches have raised the standards of performance for rotating equipment by providing robust, cost effective, easy to implement magnetic bearing solutions. Use of magnetic bearings in ships can be more advantag...

  4. Selecting the best stable isotope mixing model to estimate grizzly bear diets in the Greater Yellowstone Ecosystem.

    Directory of Open Access Journals (Sweden)

    John B Hopkins

    Full Text Available Past research indicates that whitebark pine seeds are a critical food source for Threatened grizzly bears (Ursus arctos in the Greater Yellowstone Ecosystem (GYE. In recent decades, whitebark pine forests have declined markedly due to pine beetle infestation, invasive blister rust, and landscape-level fires. To date, no study has reliably estimated the contribution of whitebark pine seeds to the diets of grizzlies through time. We used stable isotope ratios (expressed as δ13C, δ15N, and δ34S values measured in grizzly bear hair and their major food sources to estimate the diets of grizzlies sampled in Cooke City Basin, Montana. We found that stable isotope mixing models that included different combinations of stable isotope values for bears and their foods generated similar proportional dietary contributions. Estimates generated by our top model suggest that whitebark pine seeds (35±10% and other plant foods (56±10% were more important than meat (9±8% to grizzly bears sampled in the study area. Stable isotope values measured in bear hair collected elsewhere in the GYE and North America support our conclusions about plant-based foraging. We recommend that researchers consider model selection when estimating the diets of animals using stable isotope mixing models. We also urge researchers to use the new statistical framework described here to estimate the dietary responses of grizzlies to declines in whitebark pine seeds and other important food sources through time in the GYE (e.g., cutthroat trout, as such information could be useful in predicting how the population will adapt to future environmental change.

  5. Modelling and construction of a compact 500 kg HTS magnetic bearing

    International Nuclear Information System (INIS)

    Werfel, F N; Floegel-Delor, U; Rothfeld, R; Goebel, B; Wippich, D; Riedel, T

    2005-01-01

    The progress of heavy-load HTS bearings depends on improvements in design, material quality and reliable cooling. We have constructed, manufactured and tested a 200 mm HTS journal bearing with a thermally encapsulated YBCO ring. For maximum force the larger gap due to the bearing cryostat (>4 mm) requires adjustment of the magnetic excitation pole distance and the Fe collector shim thickness. HTS material progress is obtained by top-seeded single- or multiple-grain growth which increases the averaged trapped magnetic flux density. Successful YBCO ring growth with radial c axis distribution by seeding the inner ring surface has been performed. The encapsulation ensures a substantially reduced cryogenic effort and stabilizes bearing operation at 78-79 K

  6. The First Korean Case of Beare-Stevenson Syndrome with a Tyr375Cys Mutation in the Fibroblast Growth Factor Receptor 2 Gene

    OpenAIRE

    Eun, So-Hee; Ha, Ki Ssu; Je, Bo-Kyung; Lee, Eung Seok; Choi, Byung Min; Lee, Jung Hwa; Eun, Baik-Lin; Yoo, Kee Hwan

    2007-01-01

    Here we report the first case of a Korean infant with a cloverleaf-shaped craniosynostosis, in which the diagnosis of Beare-Stevenson syndrome was suspected upon observation of the typical morphological features. This infant exhibited craniofacial anomalies, ocular proptosis, cutis gyrata, acanthosis nigricans, prominent umbilical stump, furrowed palms and soles, hypospadia, and sacral skin tag coupled with dermal sinus tract. Brain magnetic resonance imaging revealed that the patient also ha...

  7. Prognosticating fault development rate in wind turbine generator bearings using local trend models

    DEFF Research Database (Denmark)

    Skrimpas, Georgios Alexandros; Palou, Jonel; Sweeney, Christian Walsted

    2016-01-01

    Generator bearing defects, e.g. ball, inner and outer race defects, are ranked among the most frequent mechanical failures encountered in wind turbines. Diagnosis and prognosis of bearing faults can be successfully implemented using vibration based condition monitoring systems, where tracking...... to maintenance planning and component replacement. The above approach offers numerous benefits from financial and operational perspective, such as increased availability, uptower repairs and minimization of secondary and catastrophic damages. In this work, a non-speed related condition indicator, measuring...

  8. Predicting the response of high damping rubber bearings using simplified models and finite element analysis

    International Nuclear Information System (INIS)

    Fuller, K.N.G.; Gough, J.; Ahmadi, H.R.

    1993-01-01

    The International Atomic Energy Agency has initiated a co-ordinated research programme on implementation of base-isolation for nuclear structures. This paper discusses two areas relevant to modelling elastomeric base-isolators. These are the use of simplified models to predict the response of isolated structures to earthquake inputs and finite element analysis for calculating the stress distributions within the isolators. In the former, a curvilinear hysteretic model of the high damping natural rubber able to accommodate the stiffening of the rubber at large shear deflections is presented. Its predictions of structural accelerations and bearing displacement produced by design earthquakes and those above the design level are compared with those using a linear spring and dashpot model. A comparison has been made between two finite element analyses using MARC and ABAQUS of the force-deformation behaviour of a single disc of rubber bonded on both sides. The disc was loaded both in compression and shear. Two forms of strain energy functions were used namely Mooney-RivIin and Ogden. The agreement between MARC and ABAQUS for the Mooney-Rivlin model for the material was very good. This was not however the case for the Ogden model and a difference of 25% in the maximum vertical deflection of the disc under 200kN load was observed. The need for a 'benchmark' problem is identified. This could be used to establish the accuracy of the finite element solvers. A problem based on the work of Rivlin on the force-deformation behaviour of cylinder of rubber under torsion is nominated. An appraisal of strain energy functions based on Mooney-RivIin formulations is carried out. It is shown that even for a five term series the strain energy function is incapable of catering for the rapid change of modulus at small strains both for simple and pure shear modes of deformation. This function models tension/compression data much better. The work identifies the need for evaluating other forms

  9. A New Analysis Tool Assessment for Rotordynamic Modeling of Gas Foil Bearings

    Science.gov (United States)

    Howard, Samuel A.; SanAndres, Luis

    2010-01-01

    Gas foil bearings offer several advantages over traditional bearing types that make them attractive for use in high-speed turbomachinery. They can operate at very high temperatures, require no lubrication supply (oil pumps, seals, etc.), exhibit very long life with no maintenance, and once operating airborne, have very low power loss. The use of gas foil bearings in high-speed turbomachinery has been accelerating in recent years, although the pace has been slow. One of the contributing factors to the slow growth has been a lack of analysis tools, benchmarked to measurements, to predict gas foil bearing behavior in rotating machinery. To address this shortcoming, NASA Glenn Research Center (GRC) has supported the development of analytical tools to predict gas foil bearing performance. One of the codes has the capability to predict rotordynamic coefficients, power loss, film thickness, structural deformation, and more. The current paper presents an assessment of the predictive capability of the code, named XLGFBTH (Texas A&M University). A test rig at GRC is used as a simulated case study to compare rotordynamic analysis using output from the code to actual rotor response as measured in the test rig. The test rig rotor is supported on two gas foil journal bearings manufactured at GRC, with all pertinent geometry disclosed. The resulting comparison shows that the rotordynamic coefficients calculated using XLGFBTH represent the dynamics of the system reasonably well, especially as they pertain to predicting critical speeds.

  10. A quantitative quasispecies theory-based model of virus escape mutation under immune selection.

    Science.gov (United States)

    Woo, Hyung-June; Reifman, Jaques

    2012-08-07

    Viral infections involve a complex interplay of the immune response and escape mutation of the virus quasispecies inside a single host. Although fundamental aspects of such a balance of mutation and selection pressure have been established by the quasispecies theory decades ago, its implications have largely remained qualitative. Here, we present a quantitative approach to model the virus evolution under cytotoxic T-lymphocyte immune response. The virus quasispecies dynamics are explicitly represented by mutations in the combined sequence space of a set of epitopes within the viral genome. We stochastically simulated the growth of a viral population originating from a single wild-type founder virus and its recognition and clearance by the immune response, as well as the expansion of its genetic diversity. Applied to the immune escape of a simian immunodeficiency virus epitope, model predictions were quantitatively comparable to the experimental data. Within the model parameter space, we found two qualitatively different regimes of infectious disease pathogenesis, each representing alternative fates of the immune response: It can clear the infection in finite time or eventually be overwhelmed by viral growth and escape mutation. The latter regime exhibits the characteristic disease progression pattern of human immunodeficiency virus, while the former is bounded by maximum mutation rates that can be suppressed by the immune response. Our results demonstrate that, by explicitly representing epitope mutations and thus providing a genotype-phenotype map, the quasispecies theory can form the basis of a detailed sequence-specific model of real-world viral pathogens evolving under immune selection.

  11. Modeling the formation of methane hydrate-bearing intervals in fine-grained sediments

    Energy Technology Data Exchange (ETDEWEB)

    Malinverno, Alberto; Cook, Ann; Daigle, Hugh

    2016-09-30

    Sediment grain size exerts a fundamental control on how methane hydrates are distributed within the pore space. Fine-grained muds are the predominant sediments in continental margins, and hydrates in these sediments have often been observed in semi-vertical veins and fractures. In several instances, these hydrate veins/fractures are found in discrete depth intervals a few tens meters thick within the gas hydrate stability zone (GHSZ) surrounded by hydrate-free sediments above and below. As they are not obviously connected with free gas occurring beneath the base of the GHSZ, these isolated hydrate-bearing intervals have been interpreted as formed by microbial methane generated in situ. To investigate further the formation of these hydrate deposits, we applied a time-dependent advection-diffusion-reaction model that includes the effects of sedimentation, solute diffusion, and microbial methane generation. The microbial methane generation term depends on the amount of metabolizable organic carbon deposited at the seafloor, which is degraded at a prescribed rate resulting in methane formation beneath the sulfate reduction zone. In the model, methane hydrate precipitates once the dissolved methane concentration is greater than solubility, or hydrate dissolves if concentration goes below solubility. If the deposition of organic carbon at the seafloor is kept constant in time, we found that the predicted amounts of hydrate formed in discrete intervals within the GHSZ are much less than those estimated from observations. We then investigated the effect of temporal variations in the deposition of organic carbon. If greater amounts of organic carbon are deposited during some time interval, methane generation is enhanced during burial in the corresponding sediment interval. With variations in organic carbon deposition that are consistent with observations in continental margin sediments, we were able to reproduce the methane hydrate contents estimated in discrete depth

  12. Journal bearing

    Science.gov (United States)

    Menke, John R.; Boeker, Gilbert F.

    1976-05-11

    1. An improved journal bearing comprising in combination a non-rotatable cylindrical bearing member having a first bearing surface, a rotatable cylindrical bearing member having a confronting second bearing surface having a plurality of bearing elements, a source of lubricant adjacent said bearing elements for supplying lubricant thereto, each bearing element consisting of a pair of elongated relatively shallowly depressed surfaces lying in a cylindrical surface co-axial with the non-depressed surface and diverging from one another in the direction of rotation and obliquely arranged with respect to the axis of rotation of said rotatable member to cause a flow of lubricant longitudinally along said depressed surfaces from their distal ends toward their proximal ends as said bearing members are rotated relative to one another, each depressed surface subtending a radial angle of less than 360.degree., and means for rotating said rotatable bearing member to cause the lubricant to flow across and along said depressed surfaces, the flow of lubricant being impeded by the non-depressed portions of said second bearing surface to cause an increase in the lubricant pressure.

  13. Models of frequency-dependent selection with mutation from parental alleles.

    Science.gov (United States)

    Trotter, Meredith V; Spencer, Hamish G

    2013-09-01

    Frequency-dependent selection (FDS) remains a common heuristic explanation for the maintenance of genetic variation in natural populations. The pairwise-interaction model (PIM) is a well-studied general model of frequency-dependent selection, which assumes that a genotype's fitness is a function of within-population intergenotypic interactions. Previous theoretical work indicated that this type of model is able to sustain large numbers of alleles at a single locus when it incorporates recurrent mutation. These studies, however, have ignored the impact of the distribution of fitness effects of new mutations on the dynamics and end results of polymorphism construction. We suggest that a natural way to model mutation would be to assume mutant fitness is related to the fitness of the parental allele, i.e., the existing allele from which the mutant arose. Here we examine the numbers and distributions of fitnesses and alleles produced by construction under the PIM with mutation from parental alleles and the impacts on such measures due to different methods of generating mutant fitnesses. We find that, in comparison with previous results, generating mutants from existing alleles lowers the average number of alleles likely to be observed in a system subject to FDS, but produces polymorphisms that are highly stable and have realistic allele-frequency distributions.

  14. Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears

    DEFF Research Database (Denmark)

    Liu, Shiping; Lorenzen, Eline D.; Fumagalli, Matteo

    2014-01-01

    Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyperlipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show...... that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization...... of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk...

  15. Mathematical Model and Analysis of the Water-Lubricated Hydrostatic Journal Bearings considering the Translational and Tilting Motions

    Directory of Open Access Journals (Sweden)

    Hui-Hui Feng

    2014-01-01

    Full Text Available The water-lubricated bearings have been paid attention for their advantages to reduce the power loss and temperature rise and increase load capacity at high speed. To fully study the complete dynamic coefficients of two water-lubricated, hydrostatic journal bearings used to support a rigid rotor, a four-degree-of-freedom model considering the translational and tilting motion is presented. The effects of tilting ratio, rotary speed, and eccentricity ratio on the static and dynamic performances of the bearings are investigated. The bulk turbulent Reynolds equation is adopted. The finite difference method and a linear perturbation method are used to calculate the zeroth- and first-order pressure fields to obtain the static and dynamic coefficients. The results suggest that when the tilting ratio is smaller than 0.4 or the eccentricity ratio is smaller than 0.1, the static and dynamic characteristics are relatively insensitive to the tilting and eccentricity ratios; however, for larger tilting or eccentricity ratios, the tilting and eccentric effects should be fully considered. Meanwhile, the rotary speed significantly affects the performance of the hydrostatic, water-lubricated bearings.

  16. Transgenic rat model of neurodegeneration caused by mutation in the TDP gene.

    Science.gov (United States)

    Zhou, Hongxia; Huang, Cao; Chen, Han; Wang, Dian; Landel, Carlisle P; Xia, Pedro Yuxing; Bowser, Robert; Liu, Yong-Jian; Xia, Xu Gang

    2010-03-26

    TDP-43 proteinopathies have been observed in a wide range of neurodegenerative diseases. Mutations in the gene encoding TDP-43 (i.e., TDP) have been identified in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobe degeneration associated with motor neuron disease. To study the consequences of TDP mutation in an intact system, we created transgenic rats expressing normal human TDP or a mutant form of human TDP with a M337V substitution. Overexpression of mutant, but not normal, TDP caused widespread neurodegeneration that predominantly affected the motor system. TDP mutation reproduced ALS phenotypes in transgenic rats, as seen by progressive degeneration of motor neurons and denervation atrophy of skeletal muscles. This robust rat model also recapitulated features of TDP-43 proteinopathies including the formation of TDP-43 inclusions, cytoplasmic localization of phosphorylated TDP-43, and fragmentation of TDP-43 protein. TDP transgenic rats will be useful for deciphering the mechanisms underlying TDP-43-related neurodegenerative diseases.

  17. Active tilting-pad journal bearings supporting flexible rotors: Part II–The model-based feedback-controlled lubrication

    DEFF Research Database (Denmark)

    Salazar, Jorge Andrés González; Santos, Ilmar

    2017-01-01

    This is part II of a twofold paper series dealing with the design and implementation of model-based controllers meant for assisting the hybrid and developing the feedback-controlled lubrication regimes in active tilting pad journal bearings (active TPJBs). In both papers theoretical and experimen...... derived in part I. Results show further suppression of resonant vibrations when using the feedback-controlled or active lubrication, overweighting the reduction already achieved with hybrid lubrication, thus improving the whole machine dynamic performance.......This is part II of a twofold paper series dealing with the design and implementation of model-based controllers meant for assisting the hybrid and developing the feedback-controlled lubrication regimes in active tilting pad journal bearings (active TPJBs). In both papers theoretical...... and experimental analyses are presented with focus on the reduction of rotor lateral vibration. This part is devoted to synthesising model-based LQG optimal controllers (LQR regulator + Kalman Filter) for the feedback-controlled lubrication and is based upon the mathematical model of the rotor-bearing system...

  18. Pathogen Mutation Modeled by Competition Between Site and Bond Percolation

    Science.gov (United States)

    Hébert-Dufresne, Laurent; Patterson-Lomba, Oscar; Goerg, Georg M.; Althouse, Benjamin M.

    2013-03-01

    While disease propagation is a main focus of network science, its coevolution with treatment has yet to be studied in this framework. We present a mean-field and stochastic analysis of an epidemic model with antiviral administration and resistance development. We show how this model maps to a coevolutive competition between site and bond percolation featuring hysteresis and both second- and first-order phase transitions. The latter, whose existence on networks is a long-standing question, imply that a microscopic change in infection rate can lead to macroscopic jumps in expected epidemic size.

  19. Species abundance distributions in neutral models with immigration or mutation and general lifetimes.

    Science.gov (United States)

    Lambert, Amaury

    2011-07-01

    We consider a general, neutral, dynamical model of biodiversity. Individuals have i.i.d. lifetime durations, which are not necessarily exponentially distributed, and each individual gives birth independently at constant rate λ. Thus, the population size is a homogeneous, binary Crump-Mode-Jagers process (which is not necessarily a Markov process). We assume that types are clonally inherited. We consider two classes of speciation models in this setting. In the immigration model, new individuals of an entirely new species singly enter the population at constant rate μ (e.g., from the mainland into the island). In the mutation model, each individual independently experiences point mutations in its germ line, at constant rate θ. We are interested in the species abundance distribution, i.e., in the numbers, denoted I(n)(k) in the immigration model and A(n)(k) in the mutation model, of species represented by k individuals, k = 1, 2, . . . , n, when there are n individuals in the total population. In the immigration model, we prove that the numbers (I(t)(k); k ≥ 1) of species represented by k individuals at time t, are independent Poisson variables with parameters as in Fisher's log-series. When conditioning on the total size of the population to equal n, this results in species abundance distributions given by Ewens' sampling formula. In particular, I(n)(k) converges as n → ∞ to a Poisson r.v. with mean γ/k, where γ : = μ/λ. In the mutation model, as n → ∞, we obtain the almost sure convergence of n (-1) A(n)(k) to a nonrandom explicit constant. In the case of a critical, linear birth-death process, this constant is given by Fisher's log-series, namely n(-1) A(n)(k) converges to α(k)/k, where α : = λ/(λ + θ). In both models, the abundances of the most abundant species are briefly discussed.

  20. Resilience and risk: a demographic model to inform conservation planning for polar bears

    Science.gov (United States)

    Regehr, Eric V.; Wilson, Ryan R.; Rode, Karyn D.; Runge, Michael C.

    2015-01-01

    Climate change is having widespread ecological effects, including loss of Arctic sea ice. This has led to listing of the polar bear (Ursus maritimus) and other ice-dependent marine mammals under the U.S. Endangered Species Act (ESA). Methods are needed to evaluate the effects of climate change on population persistence to inform recovery planning for listed species. For polar bears, this includes understanding interactions between climate and secondary factors, such as subsistence harvest, which provide economic, nutritional, or cultural value to humans.

  1. Complex double-mass dynamic model of rotor on thrust foil gas dynamic bearings

    Science.gov (United States)

    Sytin, A.; Babin, A.; Vasin, S.

    2017-08-01

    The present paper considers simulation of a rotor’s dynamics behaviour on thrust foil gas dynamic bearings based on simultaneous solution of gas dynamics differential equations, equations of theory of elasticity, motion equations and some additional equations. A double-mass dynamic system was considered during the rotor’s motion simulation which allows not only evaluation of rotor’s dynamic behaviour, but also to evaluate the influence of operational and load parameters on the dynamics of the rotor-bearing system.

  2. Reconstructing pedigrees: some identifiability questions for a recombination-mutation model.

    Science.gov (United States)

    Thatte, Bhalchandra D

    2013-01-01

    Pedigrees are directed acyclic graphs that represent ancestral relationships between individuals in a population. Based on a schematic recombination process, we describe two simple Markov models for sequences evolving on pedigrees--Model R (recombinations without mutations) and Model RM (recombinations with mutations). For these models, we ask an identifiability question: is it possible to construct a pedigree from the joint probability distribution of extant sequences? We present partial identifiability results for general pedigrees: we show that when the crossover probabilities are sufficiently small, certain spanning subgraph sequences can be counted from the joint distribution of extant sequences. We demonstrate how pedigrees that earlier seemed difficult to distinguish are distinguished by counting their spanning subgraph sequences.

  3. Mapping polar bear maternal denning habitat in the National Petroleum Reserve -- Alaska with an IfSAR digital terrain model

    Science.gov (United States)

    Durner, George M.; Simac, Kristin S.; Amstrup, Steven C.

    2013-01-01

    The National Petroleum Reserve–Alaska (NPR-A) in northeastern Alaska provides winter maternal denning habitat for polar bears (Ursus maritimus) and also has high potential for recoverable hydrocarbons. Denning polar bears exposed to human activities may abandon their dens before their young are able to survive the severity of Arctic winter weather. To ensure that wintertime petroleum activities do not threaten polar bears, managers need to know the distribution of landscape features in which maternal dens are likely to occur. Here, we present a map of potential denning habitat within the NPR-A. We used a fine-grain digital elevation model derived from Interferometric Synthetic Aperture Radar (IfSAR) to generate a map of putative denning habitat. We then tested the map’s ability to identify polar bear denning habitat on the landscape. Our final map correctly identified 82% of denning habitat estimated to be within the NPR-A. Mapped denning habitat comprised 19.7 km2 (0.1% of the study area) and was widely dispersed. Though mapping denning habitat with IfSAR data was as effective as mapping with the photogrammetric methods used for other regions of the Alaskan Arctic coastal plain, the use of GIS to analyze IfSAR data allowed greater objectivity and flexibility with less manual labor. Analytical advantages and performance equivalent to that of manual cartographic methods suggest that the use of IfSAR data to identify polar bear maternal denning habitat is a better management tool in the NPR-A and wherever such data may be available.

  4. Modeling and experimental assessment of a buried Leu–Ile mutation in dengue envelope domain III

    International Nuclear Information System (INIS)

    Kulkarni, Manjiri R.; Numoto, Nobutaka; Ito, Nobutoshi; Kuroda, Yutaka

    2016-01-01

    Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4_L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile 387 conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype’s ED3 is used as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile 387 confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4_L387I at 2 Å resolution. Ile 387 indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task. - Highlights: • We mutated L387I of DEN4 ED3 and examined its effects on structure and stability. • We modeled the side-chain of Ile 387 using DEN4 ED3's structure as a template. • We determined the crystal structure of DEN4_L387I and confirmed the modeling. • Side-chain repacking occurring around Ile 387 involved >3 inter-connected residues. • These results explained why L387I mutation in DEN4 ED3 conserves thermostability.

  5. Determination of fitness components of flies bearing the recessive lethal l(2)M167DTS mutation with dominant heat sensitivity in artificial Drosophila melanogaster populations

    Czech Academy of Sciences Publication Activity Database

    Kulikov, A. M.; Kuznetsov, A.; Marec, František; Mitrofanov, V. G.

    2005-01-01

    Roč. 41, č. 6 (2005), s. 620-629 ISSN 1022-7954 Grant - others:Russian Foundation for Basic Research(RU) 02-04-50021; Program of the Presidium of the Russian Academy of Sciences "Dynamics of Gene Pools in Plants, Animals, and Humans"(RU) 10002-251/P-24/154-150/2004-04-111 Institutional research plan: CEZ:AV0Z50070508 Keywords : mutation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.240, year: 2005

  6. GAS BEARING

    Science.gov (United States)

    Skarstrom, C.W.

    1960-09-01

    A gas lubricated bearing for a rotating shaft is described. The assembly comprises a stationary collar having an annular member resiliently supported thereon. The collar and annular member are provided with cooperating gas passages arranged for admission of pressurized gas which supports and lubricates a bearing block fixed to the rotatable shaft. The resilient means for the annular member support the latter against movement away from the bearing block when the assembly is in operation.

  7. Thrust bearing

    Science.gov (United States)

    Anderson, W. J. (Inventor)

    1976-01-01

    A gas lubricated thrust bearing is described which employs relatively rigid inwardly cantilevered spokes carrying a relatively resilient annular member or annulus. This annulus acts as a beam on which are mounted bearing pads. The resilience of the beam mount causes the pads to accept the load and, with proper design, responds to a rotating thrust-transmitting collar by creating a gas film between the pads and the thrust collar. The bearing may be arranged for load equalization thereby avoiding the necessity of gimbal mounts or the like for the bearing. It may also be arranged to respond to rotation in one or both directions.

  8. Discovery of 2,4-diarylaminopyrimidines bearing a resorcinol motif as novel ALK inhibitors to overcome the G1202R resistant mutation.

    Science.gov (United States)

    Geng, Kaijun; Xia, Zongjun; Ji, Yinchun; Zhang, Ruisi Ruthy; Sun, Deqiao; Ai, Jing; Song, Zilan; Geng, Meiyu; Zhang, Ao

    2018-01-20

    To address drug resistance caused by ALK kinase mutations, especially the most refractory and predominant mutation G1202R for the second-generation ALK inhibitor, a series of new diarylaminopyrimidine analogues were designed by incorporating a resorcinol moiety (A-ring) to interact the ALK kinase domain where the G1202R is located. Compound 12d turns out as the most potent with IC 50 values of 1.7, 3.5, and 1.8 nM against ALK wild type, gatekeeper mutant L1196M, and the G1202R mutant, respectively. More importantly, compound 12d has excellent inhibitory effects against the proliferation of BaF3 cells specifically expressing ALK wild type, gatekeeper L1196M, and the most challenging mutant G1202R, with IC 50 values all less than 1.5 nM. Collectively, compound 12d is worthy of further investigation as a new more potent third-generation ALK inhibitor to circumvent drug resistance of both the first-generation and the second-generation inhibitors. Copyright © 2017. Published by Elsevier Masson SAS.

  9. A Comparison of Grizzly Bear Demographic Parameters Estimated from Non-Spatial and Spatial Open Population Capture-Recapture Models.

    Science.gov (United States)

    Whittington, Jesse; Sawaya, Michael A

    2015-01-01

    Capture-recapture studies are frequently used to monitor the status and trends of wildlife populations. Detection histories from individual animals are used to estimate probability of detection and abundance or density. The accuracy of abundance and density estimates depends on the ability to model factors affecting detection probability. Non-spatial capture-recapture models have recently evolved into spatial capture-recapture models that directly include the effect of distances between an animal's home range centre and trap locations on detection probability. Most studies comparing non-spatial and spatial capture-recapture biases focussed on single year models and no studies have compared the accuracy of demographic parameter estimates from open population models. We applied open population non-spatial and spatial capture-recapture models to three years of grizzly bear DNA-based data from Banff National Park and simulated data sets. The two models produced similar estimates of grizzly bear apparent survival, per capita recruitment, and population growth rates but the spatial capture-recapture models had better fit. Simulations showed that spatial capture-recapture models produced more accurate parameter estimates with better credible interval coverage than non-spatial capture-recapture models. Non-spatial capture-recapture models produced negatively biased estimates of apparent survival and positively biased estimates of per capita recruitment. The spatial capture-recapture grizzly bear population growth rates and 95% highest posterior density averaged across the three years were 0.925 (0.786-1.071) for females, 0.844 (0.703-0.975) for males, and 0.882 (0.779-0.981) for females and males combined. The non-spatial capture-recapture population growth rates were 0.894 (0.758-1.024) for females, 0.825 (0.700-0.948) for males, and 0.863 (0.771-0.957) for both sexes. The combination of low densities, low reproductive rates, and predominantly negative population growth

  10. Somatic mutations in Tradescantia as a model system for studying the effects of the environmental agents

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.

    1986-01-01

    The application of the plant model system for studying the biological effects of ionizing radiation and chemical mutagens is presented. The model system is based on the somatic mutation frequency in stamen hair cells of Tradescantia clones heterosygous for flower color. The interaction of chemical mutagens with radiation in the induction of somatic mutations was investigated. The results demonstrate the synergistic interaction between radiation and chemical mutagens like ethyl methanesulfonate and di-bromoethane. The synergistic effect is clearly manifested after combined treatment with radiation and chemicals. In the low dose region the effect depends on the radiation dose and chemical exposure. Other results show the influence of the fluoride treatment on the radiation effect. The fluoride treatment is likely to alter the DNA double strand breaks repair processes. Additionally the usefulness of the model system for studying the mutagenic effectiveness of the pollution in the ambient air is presented. 148 refs. (author)

  11. Risk modeling and screening for BRCA1 mutations among Filipino breast cancer patients

    International Nuclear Information System (INIS)

    Nato, Alejandro Q. Jr.

    2003-03-01

    Breast cancer susceptibility gene, type 1(BRCA1) has been thought to be responsible for ∼45% of families with multiple breast carcinomas and for ∼80% of breast and ovarian cancer families. In this study, we investigated 34 familial Filipino breast cancer (BC) patients to: (a) estimate breast cancer risks and BRCA1/2 mutation carrier probabilities using risk assessment and prior probability models, respectively; (b) screen for putative polymorphisms at selected smaller exons of BRCA1 by single-strand conformation polymorphism (SSCP) analysis; (c) screen for truncated mutations at BRCA1 exon 11 by radioactive protein truncation test (PTT); and (d) estimate posterior probabilities upon incorporation of screening results. SSCP analysis revealed 8 unique putative polymorphisms. Low prevalence of unique putative polymorphisms at exon 2, 5, 17, and 22 may indicate probable mutations. Contrastingly, high prevalence of unique putative polymorphisms at exons 13, 15, and 16 may suggest true polymorphisms which are biologically insignificant. PTT, DHPLC, and sequence analyses revealed a novel mutation in exon 11 involving GT insertion that resulted to a stop codon which generated a 29.7 kDa truncated protein product. This is the second documented mutation in BRCA1 exon 11 in a Filipino BC patient since 1998. Initial genotype-phenotype correlations in Filipino BC patients may be elucidated based on screening tests performed. Our results corroborate the findings of a study on unselected incident Filipino BC cases where the reported prevalence of BRCA1 mutation is low. The higher prevalence of putative polypmorphisms may be attributed to the increased stringency in patient prospecting. The Gail, Claus, and BRCAPRO models can be utilized to estimate BC risk in unaffected high-risk individuals but validation is needed. Most of the BRCAPRO and Myriad.com prior probability estimates coincide with the presence of BRCA1 mutation and/or putative polymorphisms. This pioneering

  12. A 3D finite element-based model order reduction method for parametric resonance and whirling analysis of anisotropic rotor-bearing systems

    Science.gov (United States)

    Wang, Shuai; Wang, Yu; Zi, Yanyang; He, Zhengjia

    2015-12-01

    A generalized and efficient model for rotating anisotropic rotor-bearing systems is presented in this paper with full considerations of the system's anisotropy in stiffness, inertia and damping. Based on the 3D finite element model and the model order reduction method, the effects of anisotropy in shaft and bearings on the forced response and whirling of anisotropic rotor-bearing systems are systematically investigated. First, the coefficients of journal bearings are transformed from the fixed frame to the rotating one. Due to the anisotropy in shaft and bearings, the motion is governed by differential equations with periodically time-variant coefficients. Then, a free-interface complex component mode synthesis (CMS) method is employed to generate efficient reduced-order models (ROM) for the periodically time-variant systems. In order to solve the obtained equations, a variant of Hill's method for systems with multiple harmonic excitations is developed. Four dimensionless parameters are defined to quantify the types and levels of anisotropy of bearings. Finally, the effects of the four types of anisotropy on the forced response and whirl orbits are studied. Numerical results show that the anisotropy of bearings in stiffness splits the sole resonant peak into two isolated ones, but the anisotropy of bearings in damping coefficients mainly affect the response amplitudes. Moreover, the whirl orbits become much more complex when the shaft and bearings are both anisotropic. In addition, the cross-coupling stiffness coefficients of bearings significantly affect the dynamic behaviors of the systems and cannot be neglected, though they are often much smaller than the principle stiffness terms.

  13. THCM Coupled Model for Hydrate-Bearing Sediments: Data Analysis and Design of New Field Experiments (Marine and Permafrost Settings)

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, Marcelo J. [Texas A & M Univ., College Station, TX (United States); Santamarina, J. Carlos [King Abdullah Univ. of Science and Technology (Saudi Arabia)

    2017-02-14

    Gas hydrates are solid compounds made of water molecules clustered around low molecular weight gas molecules such as methane, hydrogen, and carbon dioxide. Methane hydrates form under pressure (P) and temperature (T) conditions that are common in sub-permafrost layers and in deep marine sediments. Stability conditions constrain the occurrence of gas hydrates to submarine sediments and permafrost regions. The amount of technically recoverable methane trapped in gas hydrate may exceed 104tcf. Gas hydrates are a potential energy resource, can contribute to climate change, and can cause large-scale seafloor instabilities. In addition, hydrate formation can be used for CO2 sequestration (also through CO2-CH4 replacement), and efficient geological storage seals. The experimental study of hydrate bearing sediments has been hindered by the very low solubility of methane in water (lab testing), and inherent sampling difficulties associated with depressurization and thermal changes during core extraction. This situation has prompted more decisive developments in numerical modeling in order to advance the current understanding of hydrate bearing sediments, and to investigate/optimize production strategies and implications. The goals of this research has been to addresses the complex thermo-hydro-chemo-mechanical THCM coupled phenomena in hydrate-bearing sediments, using a truly coupled numerical model that incorporates sound and proven constitutive relations, satisfies fundamental conservation principles. Analytical solutions aimed at verifying the proposed code have been proposed as well. These tools will allow to better analyze available data and to further enhance the current understanding of hydrate bearing sediments in view of future field experiments and the development of production technology.

  14. Polar Bears

    Science.gov (United States)

    Amstrup, Steven C.; Douglas, David C.; Reynolds, Patricia E.; Rhode, E.B.

    2002-01-01

    Polar bears (Ursus maritimus) are hunted throughout most of their range. In addition to hunting polar bears of the Beaufort Sea region are exposed to mineral and petroleum extraction and related human activities such as shipping road-building, and seismic testing (Stirling 1990).Little was known at the start of this project about how polar bears move about in their environment, and although it was understood that many bears travel across political borders, the boundaries of populations had not been delineated (Amstrup 1986, Amstrup et al. 1986, Amstrup and DeMaster 1988, Garner et al. 1994, Amstrup 1995, Amstrup et al. 1995, Amstrup 2000).As human populations increase and demands for polar bears and other arctic resources escalate, managers must know the sizes and distributions of the polar bear populations. Resource managers also need reliable estimates of breeding rates, reproductive intervals, litter sizes, and survival of young and adults.Our objectives for this research were 1) to determine the seasonal and annual movements of polar bears in the Beaufort Sea, 2) to define the boundaries of the population(s) using this region, 3) to determine the size and status of the Beaufort Sea polar bear population, and 4) to establish reproduction and survival rates (Amstrup 2000).

  15. A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations.

    Science.gov (United States)

    Schweikardt, Thorsten; Olivares, Concepción; Solano, Francisco; Jaenicke, Elmar; García-Borrón, José Carlos; Decker, Heinz

    2007-10-01

    Tyrosinases are the first and rate-limiting enzymes in the synthesis of melanin pigments responsible for colouring hair, skin and eyes. Mutation of tyrosinases often decreases melanin production resulting in albinism, but the effects are not always understood at the molecular level. Homology modelling of mouse tyrosinase based on recently published crystal structures of non-mammalian tyrosinases provides an active site model accounting for loss-of-function mutations. According to the model, the copper-binding histidines are located in a helix bundle comprising four densely packed helices. A loop containing residues M374, S375 and V377 connects the CuA and CuB centres, with the peptide oxygens of M374 and V377 serving as hydrogen acceptors for the NH-groups of the imidazole rings of the copper-binding His367 and His180. Therefore, this loop is essential for the stability of the active site architecture. A double substitution (374)MS(375) --> (374)GG(375) or a single M374G mutation lead to a local perturbation of the protein matrix at the active site affecting the orientation of the H367 side chain, that may be unable to bind CuB reliably, resulting in loss of activity. The model also accounts for loss of function in two naturally occurring albino mutations, S380P and V393F. The hydroxyl group in S380 contributes to the correct orientation of M374, and the substitution of V393 for a bulkier phenylalanine sterically impedes correct side chain packing at the active site. Therefore, our model explains the mechanistic necessity for conservation of not only active site histidines but also adjacent amino acids in tyrosinase.

  16. Mutation-selection models of codon substitution and their use to estimate selective strengths on codon usage

    DEFF Research Database (Denmark)

    Yang, Ziheng; Nielsen, Rasmus

    2008-01-01

    to examine the null hypothesis that codon usage is due to mutation bias alone, not influenced by natural selection. Application of the test to the mammalian data led to rejection of the null hypothesis in most genes, suggesting that natural selection may be a driving force in the evolution of synonymous......Current models of codon substitution are formulated at the levels of nucleotide substitution and do not explicitly consider the separate effects of mutation and selection. They are thus incapable of inferring whether mutation or selection is responsible for evolution at silent sites. Here we...... implement a few population genetics models of codon substitution that explicitly consider mutation bias and natural selection at the DNA level. Selection on codon usage is modeled by introducing codon-fitness parameters, which together with mutation-bias parameters, predict optimal codon frequencies...

  17. Multi-mutational model for cancer based on age-time patterns of radiation effects: 2. Biological aspects

    Energy Technology Data Exchange (ETDEWEB)

    Mendelsohn, M.L.; Pierce, P.A.

    1997-09-04

    Biological properties of relevance when modeling cancers induced in the atom bomb survivors include the wide distribution of the induced cancers across all organs, their biological indistinguishability from background cancers, their rates being proportional to background cancer rates, their rates steadily increasing over at least 50 years as the survivors age, and their radiation dose response being linear. We have successfully described this array of properties with a modified Armitage-Doll model using 5 to 6 somatic mutations, no intermediate growth, and the dose-related replacement of any one of these time-driven mutations by a radiation-induced mutation. Such a model is contrasted to prevailing models that use fewer mutations combined with intervening growth. While the rationale and effectiveness of our model is compelling for carcinogenesis in the atom bomb survivors, the lack of a promotional component may limit the generality of the model for other types of human carcinogenesis.

  18. Mutational Effects and Population Dynamics During Viral Adaptation Challenge Current Models

    OpenAIRE

    Miller, Craig R.; Joyce, Paul; Wichman, Holly A.

    2011-01-01

    Adaptation in haploid organisms has been extensively modeled but little tested. Using a microvirid bacteriophage (ID11), we conducted serial passage adaptations at two bottleneck sizes (104 and 106), followed by fitness assays and whole-genome sequencing of 631 individual isolates. Extensive genetic variation was observed including 22 beneficial, several nearly neutral, and several deleterious mutations. In the three large bottleneck lines, up to eight different haplotypes were observed in sa...

  19. Signatures of mutational processes in human cancer

    NARCIS (Netherlands)

    Alexandrov, Ludmil B.; Nik-Zainal, Serena; Wedge, David C.; Aparicio, Samuel A. J. R.; Behjati, Sam; Biankin, Andrew V.; Bignell, Graham R.; Bolli, Niccolò; Borg, Ake; Børresen-Dale, Anne-Lise; Boyault, Sandrine; Burkhardt, Birgit; Butler, Adam P.; Caldas, Carlos; Davies, Helen R.; Desmedt, Christine; Eils, Roland; Eyfjörd, Jórunn Erla; Foekens, John A.; Greaves, Mel; Hosoda, Fumie; Hutter, Barbara; Ilicic, Tomislav; Imbeaud, Sandrine; Imielinsk, Marcin; Jäger, Natalie; Jones, David T. W.; Jones, David; Knappskog, Stian; Kool, Marcel; Lakhani, Sunil R.; López-Otín, Carlos; Martin, Sancha; Munshi, Nikhil C.; Nakamura, Hiromi; Northcott, Paul A.; Pajic, Marina; Papaemmanuil, Elli; Paradiso, Angelo; Pearson, John V.; Puente, Xose S.; Raine, Keiran; Ramakrishna, Manasa; Richardson, Andrea L.; Richter, Julia; Rosenstiel, Philip; Schlesner, Matthias; Schumacher, Ton N.; Span, Paul N.; Teague, Jon W.; Totoki, Yasushi; Tutt, Andrew N. J.; Valdés-Mas, Rafael; van Buuren, Marit M.; van 't Veer, Laura; Vincent-Salomon, Anne; Waddell, Nicola; Yates, Lucy R.; Zucman-Rossi, Jessica; Futreal, P. Andrew; McDermott, Ultan; Lichter, Peter; Meyerson, Matthew; Grimmond, Sean M.; Siebert, Reiner; Campo, Elías; Shibata, Tatsuhiro; Pfister, Stefan M.; Campbell, Peter J.; Stratton, Michael R.; Claviez, Alexander; Rosenwald, Andreas; Borkhardt, Arndt; Brors, Benedikt; Radlwimmer, Bernhard; Lawerenz, Chris; Lopez, Cristina; Langenberger, David; Karsch, Dennis; Lenze, Dido; Kube, Dieter; Leich, Ellen; Richter, Gesine; Korbel, Jan; Hoell, Jessica; Eils, Jürgen; Hezaveh, Kebriah; Trümper, Lorenz; Rosolowski, Maciej; Weniger, Marc; Rohde, Marius; Kreuz, Markus; Loeffler, Markus; Schilhabel, Markus; Dreyling, Martin; Hansmann, Martin-Leo; Hummel, Michael; Szczepanowski, Monika; Ammerpohl, Ole; Stadler, Peter F.; Möller, Peter; Küppers, Ralf; Haas, Siegfried; Eberth, Sonja; Schreiber, Stefan; Bernhart, Stephan H.; Hoffmann, Steve; Radomski, Sylwester; Kostezka, Ulrike; Klapper, Wolfram; Sotiriou, Christos; Larsimont, Denis; Vincent, Delphine; Maetens, Marion; Mariani, Odette; Sieuwerts, Anieta M.; Martens, John W. M.; Jonasson, Jon G.; Treilleux, Isabelle; Thomas, Emilie; Mac Grogan, Gaëtan; Mannina, Cécile; Arnould, Laurent; Burillier, Laura; Merlin, Jean-Louis; Lefebvre, Magali; Bibeau, Frédéric; Massemin, Blandine; Penault-Llorca, Frédérique; Lopez, Qian; Mathieu, Marie-Christine; Lonning, Per Eystein; Schlooz-Vries, Margrete; Tol, Jolien; van Laarhoven, Hanneke; Sweep, Fred; Bult, Peter

    2013-01-01

    All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362

  20. A mild mutator phenotype arises in a mouse model for malignancies associated with neurofibromatosis type 1

    Energy Technology Data Exchange (ETDEWEB)

    Garza, Rene [Department of Cellular and Structural Biology, University of Texas, Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900 (United States); Hudson, Robert A. [Department of Cellular and Structural Biology, University of Texas, Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900 (United States); McMahan, C. Alex [Department of Pathology, University of Texas, Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900 (United States); Walter, Christi A. [Department of Cellular and Structural Biology, University of Texas, Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900 (United States); South Texas Veterans Healthcare System, San Antonio, TX 78229 (United States); Vogel, Kristine S. [Department of Cellular and Structural Biology, University of Texas, Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900 (United States)]. E-mail: vogelk@uthscsa.edu

    2007-02-03

    Defects in genes that control DNA repair, proliferation, and apoptosis can increase genomic instability, and thus promote malignant progression. Although most tumors that arise in humans with neurofibromatosis type 1 (NF1) are benign, these individuals are at increased risk for malignant peripheral nerve sheath tumors (MPNST). To characterize additional mutations required for the development of MPNST from benign plexiform neurofibromas, we generated a mouse model for these tumors by combining targeted null mutations in Nf1 and p53, in cis. CisNf1+/-; p53+/- mice spontaneously develop PNST, and these tumors exhibit loss-of-heterozygosity at both the Nf1 and p53 loci. Because p53 has well-characterized roles in the DNA damage response, DNA repair, and apoptosis, and because DNA repair genes have been proposed to act as modifiers in NF1, we used the cisNf1+/-; p53+/- mice to determine whether a mutator phenotype arises in NF1-associated malignancies. To quantitate spontaneous mutant frequencies (MF), we crossed the Big Blue mouse, which harbors a lacI transgene, to the cisNf1+/-; p53+/- mice, and isolated genomic DNA from both tumor and normal tissues in compound heterozygotes and wild-type siblings. Many of the PNST exhibited increased mutant frequencies (MF = 4.70) when compared to normal peripheral nerve and brain (MF = 2.09); mutations occurred throughout the entire lacI gene, and included base substitutions, insertions, and deletions. Moreover, the brains, spleens, and livers of these cisNf1+/-; p53+/- animals exhibited increased mutant frequencies when compared to tissues from wild-type littermates. We conclude that a mild mutator phenotype arises in the tumors and tissues of cisNf1+/-; p53+/- mice, and propose that genomic instability influences NF1 tumor progression and disease severity.

  1. Markov Chain-Like Quantum Biological Modeling of Mutations, Aging, and Evolution

    Directory of Open Access Journals (Sweden)

    Ivan B. Djordjevic

    2015-08-01

    Full Text Available Recent evidence suggests that quantum mechanics is relevant in photosynthesis, magnetoreception, enzymatic catalytic reactions, olfactory reception, photoreception, genetics, electron-transfer in proteins, and evolution; to mention few. In our recent paper published in Life, we have derived the operator-sum representation of a biological channel based on codon basekets, and determined the quantum channel model suitable for study of the quantum biological channel capacity. However, this model is essentially memoryless and it is not able to properly model the propagation of mutation errors in time, the process of aging, and evolution of genetic information through generations. To solve for these problems, we propose novel quantum mechanical models to accurately describe the process of creation spontaneous, induced, and adaptive mutations and their propagation in time. Different biological channel models with memory, proposed in this paper, include: (i Markovian classical model, (ii Markovian-like quantum model, and (iii hybrid quantum-classical model. We then apply these models in a study of aging and evolution of quantum biological channel capacity through generations. We also discuss key differences of these models with respect to a multilevel symmetric channel-based Markovian model and a Kimura model-based Markovian process. These models are quite general and applicable to many open problems in biology, not only biological channel capacity, which is the main focus of the paper. We will show that the famous quantum Master equation approach, commonly used to describe different biological processes, is just the first-order approximation of the proposed quantum Markov chain-like model, when the observation interval tends to zero. One of the important implications of this model is that the aging phenotype becomes determined by different underlying transition probabilities in both programmed and random (damage Markov chain-like models of aging, which

  2. Radiocarbon ages and age models for the past 30,000 years in Bear Lake, Utah and Idaho

    Science.gov (United States)

    Colman, Steven M.; Rosenbaum, J.G.; Kaufman, D.S.; Dean, W.E.; McGeehin, J.P.

    2009-01-01

    Radiocarbon analyses of pollen, ostracodes, and total organic carbon (TOC) provide a reliable chronology for the sediments deposited in Bear Lake over the past 30,000 years. The differences in apparent age between TOC, pollen, and carbonate fractions are consistent and in accord with the origins of these fractions. Comparisons among different fractions indicate that pollen sample ages are the most reliable, at least for the past 15,000 years. The post-glacial radiocarbon data also agree with ages independently estimated from aspartic acid racemization in ostracodes. Ages in the red, siliclastic unit, inferred to be of last glacial age, appear to be several thousand years too old, probably because of a high proportion of reworked, refractory organic carbon in the pollen samples. Age-depth models for five piston cores and the Bear Lake drill core (BL00-1) were constructed by using two methods: quadratic equations and smooth cubic-splinefits. The two types of age models differ only in detail for individual cores, and each approach has its own advantages. Specific lithological horizons were dated in several cores and correlated among them, producing robust average ages for these horizons. The age of the correlated horizons in the red, siliclastic unit can be estimated from the age model for BL00-1, which is controlled by ages above and below the red, siliclastic unit. These ages were then transferred to the correlative horizons in the shorter piston cores, providing control for the sections of the age models in those cores in the red, siliclastic unit. These age models are the backbone for reconstructions of past environmental conditions in Bear Lake. In general, sedimentation rates in Bear Lake have been quite uniform, mostly between 0.3 and 0.8 mm yr-1 in the Holocene, and close to 0.5 mm yr-1 for the longer sedimentary record in the drill core from the deepest part of the lake. Copyright ?? 2009 The Geological Society of America.

  3. Mutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology.

    LENUS (Irish Health Repository)

    2011-01-01

    Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.

  4. Modeling and experimental assessment of a buried Leu–Ile mutation in dengue envelope domain III

    Energy Technology Data Exchange (ETDEWEB)

    Kulkarni, Manjiri R. [Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16, Nakamachi, Koganei-shi, Tokyo, 184-8588 (Japan); Numoto, Nobutaka; Ito, Nobutoshi [Department of Structural Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45, Yushima Bunkyo-ku, Tokyo, 113-8510 (Japan); Kuroda, Yutaka, E-mail: ykuroda@cc.tuat.ac.jp [Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16, Nakamachi, Koganei-shi, Tokyo, 184-8588 (Japan)

    2016-02-26

    Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4-L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile{sup 387} conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype’s ED3 is used as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile{sup 387} confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4-L387I at 2 Å resolution. Ile{sup 387} indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task. - Highlights: • We mutated L387I of DEN4 ED3 and examined its effects on structure and stability. • We modeled the side-chain of Ile{sup 387} using DEN4 ED3's structure as a template. • We determined the crystal structure of DEN4-L387I and confirmed the modeling. • Side-chain repacking occurring around Ile{sup 387} involved >3 inter-connected residues. • These results explained why L387I mutation in DEN4 ED3 conserves thermostability.

  5. Modeling the induced mutation process in bacterial cells with defects in excision repair system

    Science.gov (United States)

    Bugay, A. N.; Vasilyeva, M. A.; Krasavin, E. A.; Parkhomenko, A. Yu.

    2015-12-01

    A mathematical model of the UV-induced mutation process in Escherichia coli cells with defects in the uvrA and polA genes has been developed. The model describes in detail the reaction kinetics for the excision repair system. The number of mismatches as a result of translesion synthesis is calculated for both wild-type and mutant cells. The effect of temporal modulation of the number of single-stranded DNA during postreplication repair has been predicted. A comparison of effectiveness of different repair systems has been conducted.

  6. Modeling and Calibration for Crack Detection in Circular Shafts Supported on Bearings Using Lateral and Torsional Vibration Measurements

    Directory of Open Access Journals (Sweden)

    A. Tlaisi

    2012-01-01

    Full Text Available In this paper the requisite foundational numerical and experimental investigations that are carried out, to model the “uncracked and cracked” shaft and to identify its bending and torsional vibration responses, are reported. The cylindrical shaft used in this experimental study is continuous over two spans (with a cantilever span carrying a propeller with ball-bearing supports. During modal tests the backward end of shaft (away from the propeller end and connecting it to an electric motor, required for online monitoring is fixed to one of the test frame supports; later on this backward end will be connected to an electric motor to carry out online modal monitoring for crack identification. In the numerical study, beam elements are used for modeling the bending and torsional vibrations of the rotating shaft. The paper describes in detail the numerical “linear spring” models developed for representing the effects of “ball bearings and the (experimental test frame supports” on the vibration frequencies. Shaft response parameters are obtained using modal analysis software, LMS Test Lab, for bending vibrations monitored using accelerometers, and three “sets” of shear strain gages fixed at three different shaft locations measure the torsional vibrations. Effects of different crack depths on bending and torsional frequencies and mode shapes are investigated experimentally and numerically, and the results interpreted to give better comprehension of its vibratory behavior.

  7. Hydrodynamic Effects on Modeling and Control of a High Temperature Active Magnetic Bearing Pump with a Canned Rotor

    Energy Technology Data Exchange (ETDEWEB)

    Melin, Alexander M [ORNL; Kisner, Roger A [ORNL; Fugate, David L [ORNL; Holcomb, David Eugene [ORNL

    2015-01-01

    Embedding instrumentation and control Embedding instrumentation and control (I\\&C) at the component level in nuclear power plants can improve component performance, lifetime, and resilience by optimizing operation, reducing the constraints on physical design, and providing on-board prognostics and diagnostics. However, the extreme environments that many nuclear power plant components operate in makes embedding instrumentation and control at the component level difficult. Successfully utilizing embedded I\\&C requires developing a deep understanding of the system's dynamics and using that knowledge to overcome material and physical limitations imposed by the environment. In this paper, we will develop a coupled dynamic model of a high temperature (700 $^\\circ$C) canned rotor pump that incorporates rotordynamics, hydrodynamics, and active magnetic bearing dynamics. Then we will compare two control design methods, one that uses a simplified decoupled model of the system and another that utilizes the full coupled system model. It will be seen that utilizing all the available knowledge of the system dynamics in the controller design yield an order of magnitude improvement in the magnitude of the magnetic bearing response to disturbances at the same level of control effort, a large reduction in the settling time of the system, and a smoother control action.

  8. Calculation of water-bearing primary basalt and estimation of source mantle conditions beneath arcs: PRIMACALC2 model for WINDOWS

    Science.gov (United States)

    Kimura, Jun-Ichi; Ariskin, Alexey A.

    2014-04-01

    We present a new method for estimating the composition of water-bearing primary arc basalt and its source mantle conditions. The PRIMACALC2 model uses a thermodynamic fractional crystallization model COMAGMAT3.72 and runs with an Excel macro to examine the mantle equilibrium and trace element calculations of a primary basalt. COMAGMAT3.72 calculates magma fractionation in 0-10 kb at various compositions, pressure, oxygen fugacity, and water content, but is only applicable for forward calculations. PRIMACALC2 first calculates the provisional composition of a primary basalt from an observed magma. The basalt composition is then calculated by COMAGMAT3.72 for crystallization. Differences in elemental concentrations between observed and the closest-match calculated magmas are then adjusted in the primary basalt. Further iteration continues until the calculated magma composition converges with the observed magma, resulting in the primary basalt composition. Once the fitting is satisfied, back calculations of trace elements are made using stepwise addition of fractionated minerals. Mantle equilibrium of the primary basalt is tested using the Fo-NiO relationship of olivine in equilibrium with the primary basalt, and thus with the source mantle. Source mantle pressure, temperature, and degree of melting are estimated using petrogenetic grids based on experimental data obtained in anhydrous systems. Mantle melting temperature in a hydrous system is computed by adjusting T with a parameterization for a water-bearing system. PRIMACALC2 can be used either in dry or water-bearing arc magmas and is also applicable to mid-ocean ridge basalts and nonalkalic ocean island basalts.

  9. Computational analysis of the human sinus node action potential: model development and effects of mutations.

    Science.gov (United States)

    Fabbri, Alan; Fantini, Matteo; Wilders, Ronald; Severi, Stefano

    2017-04-01

    We constructed a comprehensive mathematical model of the spontaneous electrical activity of a human sinoatrial node (SAN) pacemaker cell, starting from the recent Severi-DiFrancesco model of rabbit SAN cells. Our model is based on electrophysiological data from isolated human SAN pacemaker cells and closely matches the action potentials and calcium transient that were recorded experimentally. Simulated ion channelopathies explain the clinically observed changes in heart rate in corresponding mutation carriers, providing an independent qualitative validation of the model. The model shows that the modulatory role of the 'funny current' (I f ) in the pacing rate of human SAN pacemaker cells is highly similar to that of rabbit SAN cells, despite its considerably lower amplitude. The model may prove useful in the design of experiments and the development of heart-rate modulating drugs. The sinoatrial node (SAN) is the normal pacemaker of the mammalian heart.  Over several decades, a large amount of data on the ionic mechanisms underlying the spontaneous electrical activity of SAN pacemaker cells has been obtained, mostly in experiments on single cells isolated from rabbit SAN. This wealth of data has allowed the development of mathematical models of the electrical activity of rabbit SAN pacemaker cells. The present study aimed to construct a comprehensive model of the electrical activity of a human SAN pacemaker cell using recently obtained electrophysiological data from human SAN pacemaker cells.  We based our model on the recent Severi-DiFrancesco model of a rabbit SAN pacemaker cell. The action potential and calcium transient of the resulting model are close to the experimentally recorded values. The model has a much smaller 'funny current' (I f ) than do rabbit cells, although its modulatory role is highly similar. Changes in pacing rate upon the implementation of mutations associated with sinus node dysfunction agree with the clinical observations. This agreement

  10. A Low Frequency Uni-variate Model for the Effective Diagnosis and Prognosis of Bearing Signals Based Upon High Frequency Data

    Science.gov (United States)

    2014-10-02

    identical conditions (for instance, in a production facility or wind turbine ), by utilising known normal behaviour of a single bearing , the...extend this analysis to non- stationary signals for wind turbine gearbox analysis by normalising for loading transitions. The signal can be broken into a...A Low Frequency Uni-variate Model for the Effective Diagnosis and Prognosis of Bearing Signals Based Upon High Frequency Data Jamie L. Godwin1

  11. Bestrophin gene mutations cause canine multifocal retinopathy: a novel animal model for best disease.

    Science.gov (United States)

    Guziewicz, Karina E; Zangerl, Barbara; Lindauer, Sarah J; Mullins, Robert F; Sandmeyer, Lynne S; Grahn, Bruce H; Stone, Edwin M; Acland, Gregory M; Aguirre, Gustavo D

    2007-05-01

    Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5'- and 3'-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting and immunocytochemistry. All exons and the flanking splice junctions were screened by direct sequencing. The clinical phenotype and pathology of cmr closely resemble lesions of BMD. Canine VMD2 spans 13.7 kb of genomic DNA on CFA18 and shows a high level of conservation among eukaryotes. The transcript is predominantly expressed in RPE/choroid and encodes bestrophin, a 580-amino acid protein of 66 kDa. Immunocytochemistry of normal canine retina demonstrated specific localization of protein to the RPE basolateral plasma membranes. Two disease-specific sequence alterations were identified in the canine VMD2 gene: a C(73)T stop mutation in cmr1 and a G(482)A missense mutation in cmr2. The authors propose these two spontaneous mutations in the canine VMD2 gene, which cause cmr, as the first naturally occurring animal model of BMD. Further development of the cmr models will permit elucidation of the complex molecular mechanism of these retinopathies and the development of potential therapies.

  12. Glesatinib Exhibits Antitumor Activity in Lung Cancer Models and Patients HarboringMETExon 14 Mutations and Overcomes Mutation-mediated Resistance to Type I MET Inhibitors in Nonclinical Models.

    Science.gov (United States)

    Engstrom, Lars D; Aranda, Ruth; Lee, Matthew; Tovar, Elizabeth A; Essenburg, Curt J; Madaj, Zachary; Chiang, Harrah; Briere, David; Hallin, Jill; Lopez-Casas, Pedro P; Baños, Natalia; Menendez, Camino; Hidalgo, Manuel; Tassell, Vanessa; Chao, Richard; Chudova, Darya I; Lanman, Richard B; Olson, Peter; Bazhenova, Lyudmilla; Patel, Sandip Pravin; Graveel, Carrie; Nishino, Mizuki; Shapiro, Geoffrey I; Peled, Nir; Awad, Mark M; Jänne, Pasi A; Christensen, James G

    2017-11-01

    Purpose: MET exon 14 deletion ( MET ex14 del) mutations represent a novel class of non-small cell lung cancer (NSCLC) driver mutations. We evaluated glesatinib, a spectrum-selective MET inhibitor exhibiting a type II binding mode, in MET ex14 del-positive nonclinical models and NSCLC patients and assessed its ability to overcome resistance to type I MET inhibitors. Experimental Design: As most MET inhibitors in clinical development bind the active site with a type I binding mode, we investigated mechanisms of acquired resistance to each MET inhibitor class utilizing in vitro and in vivo models and in glesatinib clinical trials. Results: Glesatinib inhibited MET signaling, demonstrated marked regression of MET ex14 del-driven patient-derived xenografts, and demonstrated a durable RECIST partial response in a MET ex14 del mutation-positive patient enrolled on a glesatinib clinical trial. Prolonged treatment of nonclinical models with selected MET inhibitors resulted in differences in resistance kinetics and mutations within the MET activation loop (i.e., D1228N, Y1230C/H) that conferred resistance to type I MET inhibitors, but remained sensitive to glesatinib. In vivo models exhibiting MET ex14 del/A-loop double mutations and resistance to type I inhibitors exhibited a marked response to glesatinib. Finally, a MET ex14 del mutation-positive NSCLC patient who responded to crizotinib but later relapsed, demonstrated a mixed response to glesatinib including reduction in size of a MET Y1230H mutation-positive liver metastasis and concurrent loss of detection of this mutation in plasma DNA. Conclusions: Together, these data demonstrate that glesatinib exhibits a distinct mechanism of target inhibition and can overcome resistance to type I MET inhibitors. Clin Cancer Res; 23(21); 6661-72. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Development of a modified Mooney-Rivlin constitutive model for rubber to investigate the effects of aging and marine corrosion on seismic isolated bearings

    Science.gov (United States)

    Zhao, Guifeng; Ma, Yuhong; Li, Yanmin; Luo, Jiarun; Du, Chang

    2017-10-01

    In this study, aging and marine corrosion tests of a large number of rubber material and rubber bearings have been carried out. The constitutive Mooney-Rivlin model parameters for a rubber isolated bearing have been determined. By applying the least-square method to the experimental data, the relationships between the aging time and the marine corrosion time with the constants in the constitutive model for a rubber bearing have been derived. Next, the Mooney-Rivlin model has been modified accordingly. Further, using the modified Mooney-Rivlin model and the Abaqus software, the performance of the rubber isolated bearings has been simulated. The simulation results have been compared to the experimental results so as to verify the accuracy of the modified model. The comparison shows that the maximum errors for the vertical and horizontal stiffnesses are 16.8% and 0.49%, respectively. Since these errors are considered acceptable, the accuracy of the modified constitutive model can be considered verified. The results of this study can provide theoretical support for the performance study on rubber isolated bearings under the complex ocean environment and the life-cycle performance evaluation of bridges and other offshore structures.

  14. An inducible mouse model of podocin-mutation-related nephrotic syndrome.

    Directory of Open Access Journals (Sweden)

    Mansoureh Tabatabaeifar

    Full Text Available Mutations in the NPHS2 gene, encoding podocin, cause hereditary nephrotic syndrome. The most common podocin mutation, R138Q, is associated with early disease onset and rapid progression to end-stage renal disease. Knock-in mice carrying a R140Q mutation, the mouse analogue of human R138Q, show developmental arrest of podocytes and lethal renal failure at neonatal age. Here we created a conditional podocin knock-in model named NPHS2 R140Q/-, using a tamoxifen-inducible Cre recombinase, which permits to study the effects of the mutation in postnatal life. Within the first week of R140Q hemizygosity induction the animals developed proteinuria, which peaked after 4-5 weeks. Subsequently the animals developed progressive renal failure, with a median survival time of 12 (95% CI: 11-13 weeks. Foot process fusion was observed within one week, progressing to severe and global effacement in the course of the disease. The number of podocytes per glomerulus gradually diminished to 18% compared to healthy controls 12-16 weeks after induction. The fraction of segmentally sclerosed glomeruli was 25%, 85% and 97% at 2, 4 and 8 weeks, respectively. Severe tubulointerstitial fibrosis was present at later disease stage and was correlated quantitatively with the level of proteinuria at early disease stages. While R140Q podocin mRNA expression was elevated, protein abundance was reduced by more than 50% within one week following induction. Whereas miRNA21 expression persistently increased during the first 4 weeks, miRNA-193a expression peaked 2 weeks after induction. In conclusion, the inducible R140Q-podocin mouse model is an auspicious model of the most common genetic cause of human nephrotic syndrome, with a spontaneous disease course strongly reminiscent of the human disorder. This model constitutes a valuable tool to test the efficacy of novel pharmacological interventions aimed to improve podocyte function and viability and attenuate proteinuria

  15. An Ensemble Deep Convolutional Neural Network Model with Improved D-S Evidence Fusion for Bearing Fault Diagnosis.

    Science.gov (United States)

    Li, Shaobo; Liu, Guokai; Tang, Xianghong; Lu, Jianguang; Hu, Jianjun

    2017-07-28

    Intelligent machine health monitoring and fault diagnosis are becoming increasingly important for modern manufacturing industries. Current fault diagnosis approaches mostly depend on expert-designed features for building prediction models. In this paper, we proposed IDSCNN, a novel bearing fault diagnosis algorithm based on ensemble deep convolutional neural networks and an improved Dempster-Shafer theory based evidence fusion. The convolutional neural networks take the root mean square (RMS) maps from the FFT (Fast Fourier Transformation) features of the vibration signals from two sensors as inputs. The improved D-S evidence theory is implemented via distance matrix from evidences and modified Gini Index. Extensive evaluations of the IDSCNN on the Case Western Reserve Dataset showed that our IDSCNN algorithm can achieve better fault diagnosis performance than existing machine learning methods by fusing complementary or conflicting evidences from different models and sensors and adapting to different load conditions.

  16. Graph-Theoretic Models of Mutations in the Nucleotide Binding Domain 1 of the Cystic Fibrosis Transmembrane Conductance Regulator

    Directory of Open Access Journals (Sweden)

    Debra J. Knisley

    2013-01-01

    Full Text Available Cystic fibrosis is one of the most common inherited diseases and is caused by a mutation in a membrane protein, the cystic fibrosis transmembrane conductance regulator (CFTR. This protein serves as a chloride channel and regulates the viscosity of mucus lining the ducts of a number of organs. Although much has been learned about the consequences of mutations on the energy landscape and the resulting disrupted folding pathway of CFTR, a level of understanding needed to correct the misfolding has not been achieved. The most common mutations of CFTR are located in one of two nucleotide binding domains, namely, the nucleotide binding domain 1 (NBD1. We model NBD1 using a nested graph model. The vertices in the lowest layer each represent an atom in the structure of an amino acid residue, while the vertices in the mid layer each represent the residue. The vertices in the top layer each represent a subdomain of the nucleotide binding domain. We use this model to quantify the effects of a single point mutation on the protein domain. We compare the wildtype structure with eight of the most common mutations. The graph-theoretic model provides insight into how a single point mutation can have such profound structural consequences.

  17. A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression

    Science.gov (United States)

    Giotopoulos, George; van der Weyden, Louise; Osaki, Hikari; Rust, Alistair G.; Gallipoli, Paolo; Meduri, Eshwar; Horton, Sarah J.; Chan, Wai-In; Foster, Donna; Prinjha, Rab K.; Pimanda, John E.; Tenen, Daniel G.; Vassiliou, George S.; Koschmieder, Steffen; Adams, David J.

    2015-01-01

    The introduction of highly selective ABL-tyrosine kinase inhibitors (TKIs) has revolutionized therapy for chronic myeloid leukemia (CML). However, TKIs are only efficacious in the chronic phase of the disease and effective therapies for TKI-refractory CML, or after progression to blast crisis (BC), are lacking. Whereas the chronic phase of CML is dependent on BCR-ABL, additional mutations are required for progression to BC. However, the identity of these mutations and the pathways they affect are poorly understood, hampering our ability to identify therapeutic targets and improve outcomes. Here, we describe a novel mouse model that allows identification of mechanisms of BC progression in an unbiased and tractable manner, using transposon-based insertional mutagenesis on the background of chronic phase CML. Our BC model is the first to faithfully recapitulate the phenotype, cellular and molecular biology of human CML progression. We report a heterogeneous and unique pattern of insertions identifying known and novel candidate genes and demonstrate that these pathways drive disease progression and provide potential targets for novel therapeutic strategies. Our model greatly informs the biology of CML progression and provides a potent resource for the development of candidate therapies to improve the dismal outcomes in this highly aggressive disease. PMID:26304963

  18. Modeling tissue- and mutation- specific electrophysiological effects in the long QT syndrome: role of the Purkinje fiber.

    Directory of Open Access Journals (Sweden)

    Vivek Iyer

    Full Text Available Congenital long QT syndrome is a heritable family of arrhythmias caused by mutations in 13 genes encoding ion channel complex proteins. Mounting evidence has implicated the Purkinje fiber network in the genesis of ventricular arrhythmias. In this study, we explore the hypothesis that long QT mutations can demonstrate different phenotypes depending on the tissue type of expression. Using computational models of the human ventricular myocyte and the Purkinje fiber cell, the biophysical alteration in channel function in LQT1, LQT2, LQT3, and LQT7 are modeled. We identified that the plateau potential was important in LQT1 and LQT2, in which mutation led to minimal action potential prolongation in Purkinje fiber cells. The phenotype of LQT3 mutation was dependent on the biophysical alteration induced as well as tissue type. The canonical ΔKPQ mutation causes severe action potential prolongation in both tissue types. For LQT3 mutation F1473C, characterized by shifted channel availability, a more severe phenotype was seen in Purkinje fiber cells with action potential prolongation and early afterdepolarizations. The LQT3 mutation S1904L demonstrated striking effects on action potential duration restitution and more severe action potential prolongation in Purkinje fiber cells at higher heart rates. Voltage clamp simulations highlight the mechanism of effect of these mutations in different tissue types, and impact of drug therapy is explored. We conclude that arrhythmia formation in long QT syndrome may depend not only on the basis of mutation and biophysical alteration, but also upon tissue of expression. The Purkinje fiber network may represent an important therapeutic target in the management of patients with heritable channelopathies.

  19. A mouse model of the human Fragile X syndrome I304N mutation.

    Directory of Open Access Journals (Sweden)

    Julie B Zang

    2009-12-01

    Full Text Available The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA-binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 5'UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1 in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleucine to asparagine mutation (I304N in the second FMRP KH-type RNA-binding domain, however, this single case report was complicated because the patient harbored a superimposed familial liver disease. To address these issues, we have generated a new Fragile X Syndrome mouse model in which the endogenous Fmr1 gene harbors the I304N mutation. These mice phenocopy the symptoms of Fragile X Syndrome in the existing Fmr1-null mouse, as assessed by testicular size, behavioral phenotyping, and electrophysiological assays of synaptic plasticity. I304N FMRP retains some functions, but has specifically lost RNA binding and polyribosome association; moreover, levels of the mutant protein are markedly reduced in the brain specifically at a time when synapses are forming postnatally. These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder.

  20. MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer.

    Science.gov (United States)

    García-García, Celina; Rivas, Martín A; Ibrahim, Yasir H; Calvo, María Teresa; Gris-Oliver, Albert; Rodríguez, Olga; Grueso, Judit; Antón, Pilar; Guzmán, Marta; Aura, Claudia; Nuciforo, Paolo; Jessen, Katti; Argilés, Guillem; Dienstmann, Rodrigo; Bertotti, Andrea; Trusolino, Livio; Matito, Judit; Vivancos, Ana; Chicote, Irene; Palmer, Héctor G; Tabernero, Josep; Scaltriti, Maurizio; Baselga, José; Serra, Violeta

    2015-12-15

    PI3K pathway activation occurs in concomitance with RAS/BRAF mutations in colorectal cancer, limiting the sensitivity to targeted therapies. Several clinical studies are being conducted to test the tolerability and clinical activity of dual MEK and PI3K pathway blockade in solid tumors. In the present study, we explored the efficacy of dual pathway blockade in colorectal cancer preclinical models harboring concomitant activation of the ERK and PI3K pathways. Moreover, we investigated if TP53 mutation affects the response to this therapy. Dual MEK and mTORC1/2 blockade resulted in synergistic antiproliferative effects in cell lines bearing alterations in KRAS/BRAF and PIK3CA/PTEN. Although the on-treatment cell-cycle effects were not affected by the TP53 status, a marked proapoptotic response to therapy was observed exclusively in wild-type TP53 colorectal cancer models. We further interrogated two independent panels of KRAS/BRAF- and PIK3CA/PTEN-altered cell line- and patient-derived tumor xenografts for the antitumor response toward this combination of agents. A combination response that resulted in substantial antitumor activity was exclusively observed among the wild-type TP53 models (two out of five, 40%), but there was no such response across the eight mutant TP53 models (0%). Interestingly, within a cohort of 14 patients with colorectal cancer treated with these agents for their metastatic disease, two patients with long-lasting responses (32 weeks) had TP53 wild-type tumors. Our data support that, in wild-type TP53 colorectal cancer cells with ERK and PI3K pathway alterations, MEK blockade results in potent p21 induction, preventing apoptosis to occur. In turn, mTORC1/2 inhibition blocks MEK inhibitor-mediated p21 induction, unleashing apoptosis. Clin Cancer Res; 21(24); 5499-510. ©2015 AACR. ©2015 American Association for Cancer Research.

  1. Comparison of risk assessment models of BRCA1 and BRCA2 mutation carrier in patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Rybchenko L.A.

    2013-12-01

    Full Text Available Analysis of efficiency of the algorithm BOADICEA using and Manchester scoring system to predict the carrier of BRCA1 and BRCA2 mutations in Ukranian patients with breast cancer was performed. Materials for this study were the results of clinical, imunogistological, pathogistological, genealogical, molecular genetic researches of 146 patients with breast cancer. Calculations of mutations risk were performed using BOADICEA algorithm and Manchester scoring system. In the total group of patients the area under the curve while predicting BRCA1 mutations with algorithm BOADICEA was 0.86, with Manchester scoring system - 0.84, and in calculation of the combined risk of BRCA mutations - 0.83 and 0.84, respectively. However, statistical difference between the areas of algorithms has not been established (p> 0.05, it indicates to the same discriminatory power of the test models. Better sensitivity, specificity, positive and negative predictive value of results of BOADICEA algorithm was reached in 6% of BRCA1 probability and in 8% threshold of BRCA1/2 mutations. The Manchester scoring system has showed the best operating characteristics with 6 and 13-point probability of BRCA1 and BRCA1/2 mutations respectively. Patients with probability of mutations with such thresholds may be offered molecular study of pathogenic alleles.

  2. Effects of Human Alpha-Synuclein A53T-A30P Mutations on SVZ and Local Olfactory Bulb Cell Proliferation in a Transgenic Rat Model of Parkinson Disease

    Directory of Open Access Journals (Sweden)

    Faustine Lelan

    2011-01-01

    Full Text Available A transgenic Sprague Dawley rat bearing the A30P and A53T α-synuclein (α-syn human mutations under the control of the tyrosine hydroxylase promoter was generated in order to get a better understanding of the role of the human α-syn mutations on the neuropathological events involved in the progression of the Parkinson’s disease (PD. This rat displayed olfactory deficits in the absence of motor impairments as observed in most early PD cases. In order to investigate the role of the mutated α-syn on cell proliferation, we focused on the subventricular zone (SVZ and the olfactory bulbs (OB as a change of the proliferation could affect OB function. The effect on OB dopaminergic innervation was investigated. The human α-syn co-localized in TH-positive OB neurons. No human α-syn was visualized in the SVZ. A significant increase in resident cell proliferation in the glomerular but not in the granular layers of the OB and in the SVZ was observed. TH innervation was significantly increased within the glomerular layer without an increase in the size of the glomeruli. Our rat could be a good model to investigate the role of human mutated α-syn on the development of olfactory deficits.

  3. Completing the Remedial Sequence and College-Level Credit-Bearing Math: Comparing Binary, Cumulative, and Continuation Ratio Logistic Regression Models

    Science.gov (United States)

    Davidson, J. Cody

    2016-01-01

    Mathematics is the most common subject area of remedial need and the majority of remedial math students never pass a college-level credit-bearing math class. The majorities of studies that investigate this phenomenon are conducted at community colleges and use some type of regression model; however, none have used a continuation ratio model. The…

  4. Reproductive performance in East Greenland polar bears (Ursus maritimus) may be affected by organohalogen contaminants as shown by physiologically-based pharmacokinetic (PBPK) modelling.

    Science.gov (United States)

    Sonne, Christian; Gustavson, Kim; Rigét, Frank F; Dietz, Rune; Birkved, Morten; Letcher, Robert J; Bossi, Rossana; Vorkamp, Katrin; Born, Erik W; Petersen, Gitte

    2009-12-01

    Polar bears (Ursus maritimus) feed mainly on ringed seal (Phoca hispida) and consume large quantities of blubber and consequently have one of the highest tissue concentrations of organohalogen contaminants (OHCs) worldwide. In East Greenland, studies of OHC time trends and organ system health effects, including reproductive, were conducted during 1990-2006. However, it has been difficult to determine the nature of the effects induced by OHC exposures on wild caught polar bears using body burden data and associated changes in reproductive organs and systems. We therefore conducted a risk quotient (RQ) evaluation to more quantitatively evaluate the effect risk on reproduction (embryotoxicity and teratogenicity) based on the critical body residue (CBR) concept and using a physiologically-based pharmacokinetic (PBPK) model. We applied modelling approaches to PCBs, p,p'-DDE, dieldrin, oxychlordane, HCHs, HCB, PBDEs and PFOS in East Greenland polar bears based on known OHC pharmacokinetics and dynamics in laboratory rats (Rattus rattus). The results showed that subcutaneous adipose tissue concentrations of dieldrin (range: 79-1271 ng g(-1) lw) and PCBs (range: 4128-53,923 ng g(-1) lw) reported in bears in the year 1990 were in the range to elicit possible adverse health effects on reproduction in polar bears in East Greenland (all RQs > or = 1). Similar results were found for PCBs (range: 1928-17,376 ng g(-1) lw) and PFOS (range: 104-2840 ng g(-1) ww) in the year 2000 and for dieldrin (range: 43-640 ng g(-1) lw), PCBs (range: 3491-13,243 ng g(-1) lw) and PFOS (range: 1332-6160 ng g(-1) ww) in the year 2006. The concentrations of oxychlordane, DDTs, HCB and HCHs in polar bears resulted in RQspolar bears correlated to OHC exposure are supported by the present study. This study also indicates that PBPK models may be a supportive tool in the evaluation of possible OHC-mediated health effects for Arctic wildlife.

  5. A Human Hepatocyte-Bearing Mouse: An Animal Model to Predict Drug Metabolism and Effectiveness in Humans

    Directory of Open Access Journals (Sweden)

    Katsutoshi Yoshizato

    2009-01-01

    Full Text Available Preclinical studies to predict the efficacy and safety of drugs have conventionally been conducted almost exclusively in mice and rats as rodents, despite the differences in drug metabolism between humans and rodents. Furthermore, human (ℎ viruses such as hepatitis viruses do not infect the rodent liver. A mouse bearing a liver in which the hepatocytes have been largely repopulated with ℎ-hepatocytes would overcome some of these disadvantages. We have established a practical, efficient, and large-scale production system for such mice. Accumulated evidence has demonstrated that these hepatocyte-humanized mice are a useful and reliable animal model, exhibiting ℎ-type responses in a series of in vivo drug processing (adsorption, distribution, metabolism, excretion experiments and in the infection and propagation of hepatic viruses. In this review, we present the current status of studies on chimeric mice and describe their usefulness in the study of peroxisome proliferator-activated receptors.

  6. Grease lubrication in rolling bearings

    CERN Document Server

    Lugt, Piet M

    2012-01-01

    The definitive book on the science of grease lubrication for roller and needle bearings in industrial and vehicle engineering. Grease Lubrication in Rolling Bearings provides an overview of the existing knowledge on the various aspects of grease lubrication (including lubrication systems) and the state of the art models that exist today. The book reviews the physical and chemical aspects of grease lubrication, primarily directed towards lubrication of rolling bearings. The first part of the book covers grease composition, properties and rheology, including thermal

  7. Bayesian Modeling for Genetic Anticipation in Presence of Mutational Heterogeneity: A Case Study in Lynch Syndrome

    DEFF Research Database (Denmark)

    Boonstra, Philip S; Mukherjee, Bhramar; Taylor, Jeremy M G

    2011-01-01

    birth cohorts. Using historic cancer registry data, we borrow from relative survival analysis methods to adjust for changes in age-specific incidence across birth cohorts. Our motivating case study comes from a Danish cancer register of 124 families with mutations in mismatch repair (MMR) genes known....... In this article, we posit a Bayesian approach to infer genetic anticipation under flexible random effects models for censored data that capture the effect of successive generations on AOO. Primary interest lies in the random effects. Misspecifying the distribution of random effects may result in incorrect...... to cause hereditary nonpolyposis colorectal cancer, also called Lynch syndrome (LS). We find evidence for a decrease in AOO between generations in this article. Our model predicts family-level anticipation effects that are potentially useful in genetic counseling clinics for high-risk families....

  8. The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish model

    OpenAIRE

    Yen, J.; White, R.M.; Wedge, D.C.; Van Loo, P.; De Ridder, J.; Capper, A.; Richardson, J.; Jones, D.; Raine, K.; Watson, I.R.

    2013-01-01

    Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process.

  9. Evaluation of two different models to predict BRCA1 and BRCA2 mutations in a cohort of Danish hereditary breast and/or ovarian cancer families

    DEFF Research Database (Denmark)

    Gerdes, Anne-Marie; Cruger, D G; Thomassen, M

    2006-01-01

    To meet the increasing demand for BRCA1 and BRCA2 mutation analysis, a robust system for selecting families who have a higher chance of a mutation has become important. Several models have been developed to help predict which samples are more likely to be mutation positive than others. We have...... undertaken a complete BRCA1 and BRCA2 mutation analysis in 267 Danish families with high-risk family history. We found deleterious mutations in 28% (76) of the families, 68% (52) of those in BRCA1 and 32% (24) in BRCA2. We compared our results with two popular manual models developed to estimate the chance...

  10. Dependence of the crossing time on the sequence length in the continuous-time mutation-selection model

    International Nuclear Information System (INIS)

    Gill, Wonpyong

    2010-01-01

    The dependence of the crossing time on the sequence length in the coupled and the decoupled continuous-time mutation-selection models in an asymmetric sharply-peaked landscape with a positive asymmetric parameter, r, was examined for a fixed extension parameter, E, which is defined as the average Hamming distance from the optimal allele of the initial quasispecies divided by the sequence length. Two versions of the coupled mutation-selection model, the continuous-time version and discrete-time version, were found to have the same boundary between the deterministic and the stochastic regions, which is different from the boundary between the deterministic and the stochastic regions in the decoupled continuous-time mutation-selection model. The maximum sequence length for a finite population that can evolve through the fitness barrier, e.g., within 10 6 generations in the decoupled continuous-time mutation-selection model, increased by approximately eight sequence elements with increasing population size by a factor of a thousand when E = 0.1 and r = 0.1. The crossing time for a finite population in the decoupled model in the stochastic region was shorter than the crossing time for a finite population in the coupled model, and the maximum evolvable sequence length for a finite population in the decoupled model was longer than the maximum evolvable sequence length for a finite population in the coupled model. This suggests that a mutation allowed at any time during the life cycle might be more effective than a mutation allowed only at reproduction events when a finite population transits to a higher fitness peak through the fitness barrier in an asymmetric sharply-peaked landscape.

  11. Linking changes in epithelial morphogenesis to cancer mutations using computational modeling.

    Directory of Open Access Journals (Sweden)

    Katarzyna A Rejniak

    2010-08-01

    Full Text Available Most tumors arise from epithelial tissues, such as mammary glands and lobules, and their initiation is associated with the disruption of a finely defined epithelial architecture. Progression from intraductal to invasive tumors is related to genetic mutations that occur at a subcellular level but manifest themselves as functional and morphological changes at the cellular and tissue scales, respectively. Elevated proliferation and loss of epithelial polarization are the two most noticeable changes in cell phenotypes during this process. As a result, many three-dimensional cultures of tumorigenic clones show highly aberrant morphologies when compared to regular epithelial monolayers enclosing the hollow lumen (acini. In order to shed light on phenotypic changes associated with tumor cells, we applied the bio-mechanical IBCell model of normal epithelial morphogenesis quantitatively matched to data acquired from the non-tumorigenic human mammary cell line, MCF10A. We then used a high-throughput simulation study to reveal how modifications in model parameters influence changes in the simulated architecture. Three parameters have been considered in our study, which define cell sensitivity to proliferative, apoptotic and cell-ECM adhesive cues. By mapping experimental morphologies of four MCF10A-derived cell lines carrying different oncogenic mutations onto the model parameter space, we identified changes in cellular processes potentially underlying structural modifications of these mutants. As a case study, we focused on MCF10A cells expressing an oncogenic mutant HER2-YVMA to quantitatively assess changes in cell doubling time, cell apoptotic rate, and cell sensitivity to ECM accumulation when compared to the parental non-tumorigenic cell line. By mapping in vitro mutant morphologies onto in silico ones we have generated a means of linking the morphological and molecular scales via computational modeling. Thus, IBCell in combination with 3D acini

  12. Bearing structures

    International Nuclear Information System (INIS)

    Lee, A.S.; Preece, G.E.

    1988-01-01

    A hydrostatic bearing for the lower end of the vertical shaft of a sodium pump comprises a support shell encircling the shaft and a bush located between the shell and shaft. Liquid sodium is fed from the pump outlet to the bush/shaft and bush/shell interfaces to provide hydrostatic support. The bush outer surface and the shell inner surface are of complementary part-spherical shape and the bush floats relative to the shaft so that the bush can align itself with the shaft axis. Monitoring of the relative rotational speed of the bush with respect to the shaft (such rotation being induced by the viscous drag forces present) is also performed for the purposes of detecting abnormal operation of the bearing or partial seizure, at least one magnet is rotatable with the bush, and a magnetic sensor provides an output having a frequency related to the speed of the bush. (author)

  13. Multilayer Finite-Element Model Application to Define the Bearing Structure Element Stress State of Launch Complexes

    Directory of Open Access Journals (Sweden)

    V. A. Zverev

    2016-01-01

    Full Text Available The article objective is to justify the rationale for selecting the multilayer finite element model parameters of the bearing structure of a general-purpose launch complex unit.A typical design element of the launch complex unit, i.e. a mount of the hydraulic or pneumatic cylinder, block, etc. is under consideration. The mount represents a set of the cantilevered axis and external structural cage. The most loaded element of the cage is disk to which a moment is transferred from the cantilevered axis due to actuator effort acting on it.To calculate the stress-strain state of disk was used a finite element method. Five models of disk mount were created. The only difference in models was the number of layers of the finite elements through the thickness of disk. There were models, which had one, three, five, eight, and fourteen layers of finite elements through the thickness of disk. For each model, we calculated the equivalent stresses arising from the action of the test load. Disk models were formed and calculated using the MSC Nastran complex software.The article presents results in the table to show data of equivalent stresses in each of the multi-layered models and graphically to illustrate the changing equivalent stresses through the thickness of disk.Based on these results we have given advice on selecting the proper number of layers in the model allowing a desirable accuracy of results with the lowest run time. In addition, it is concluded that there is a need to use the multi-layer models in assessing the performance of structural elements in case the stress exceeds the allowable one in their surface layers.

  14. Camshaft bearing arrangement

    Energy Technology Data Exchange (ETDEWEB)

    Aoi, K.; Ozawa, T.

    1986-06-10

    A bearing arrangement is described for the camshaft of an internal combustion engine or the like which camshaft is formed along its length in axial order with a first bearing surface, a first cam lobe, a second bearing surface, a second cam lobe, a third bearing surface, a third cam lobe and a fourth bearing surface, the improvement comprising first bearing means extending around substantially the full circumference of the first bearing surface and journaling the first bearing surface, second bearing means extending around substantially less than the circumference of the second bearing surface and journaling the second bearing surface, third bearing means extending around substantially less than the circumference of the third bearing surface and journaling the third bearing surface, and fourth bearing means extending around substantially the full circumference of the fourth bearing surface and journaling the first bearing surface.

  15. A simple model of carcinogenic mutations with time delay and diffusion.

    Science.gov (United States)

    Piotrowska, Monika Joanna; Foryś, Urszula; Bodnar, Marek; Poleszczuk, Jan

    2013-06-01

    In the paper we consider a system of delay differential equations (DDEs) of Lotka-Volterra type with diffusion reflecting mutations from normal to malignant cells. The model essentially follows the idea of Ahangar and Lin (2003) where mutations in three different environmental conditions, namely favorable, competitive and unfavorable, were considered. We focus on the unfavorable conditions that can result from a given treatment, e.g. chemotherapy. Included delay stands for the interactions between benign and other cells. We compare the dynamics of ODEs system, the system with delay and the system with delay and diffusion. We mainly focus on the dynamics when a positive steady state exists. The system which is globally stable in the case without the delay and diffusion is destabilized by increasing delay, and therefore the underlying kinetic dynamics becomes oscillatory due to a Hopf bifurcation for appropriate values of the delay. This suggests the occurrence of spatially non-homogeneous periodic solutions for the system with the delay and diffusion.

  16. Collagen mutation causes changes of the microdamage morphology in bone of an OI mouse model.

    Science.gov (United States)

    Dong, X Neil; Zoghi, Mahyar; Ran, Qitao; Wang, Xiaodu

    2010-12-01

    Previous studies have postulated that ultrastructural changes may alter the pattern and capacity of microdamage accumulation in bone. Using an osteogenesis imperfecta (OI) mouse model, this study was performed to investigate the correlation of collagen mutation with the microdamage morphology and the associated brittleness of bone. In this study, femurs from mild OI and wild type mice were fatigued under four-point bending to create microdamage in the specimens. Then, the microdamage morphology of these specimens was examined using the bulk-staining technique with basic fuchsin. Similar with the results of previous studies, it was observed that linear microcracks were formed more easily in compression, whereas diffuse damage was induced more readily in tension for both wild-type and mild-type mice. However, less diffuse damage was found in the tensile side of mild OI mouse femurs (collagen mutation) compared with those of wild type mice, showing that the microdamage morphology is correlated to the brittleness of bone. The results of this study provide direct evidence that supports the prediction made by the previous numerical simulation studies, suggesting that microdamage morphology in bone is significantly correlated with the integrity of the collagen phase. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Predictive Modeling and Mapping of Malayan Sun Bear (Helarctos malayanus) Distribution Using Maximum Entropy

    OpenAIRE

    Nazeri, Mona; Jusoff, Kamaruzaman; Madani, Nima; Mahmud, Ahmad Rodzi; Bahman, Abdul Rani; Kumar, Lalit

    2012-01-01

    One of the available tools for mapping the geographical distribution and potential suitable habitats is species distribution models. These techniques are very helpful for finding poorly known distributions of species in poorly sampled areas, such as the tropics. Maximum Entropy (MaxEnt) is a recently developed modeling method that can be successfully calibrated using a relatively small number of records. In this research, the MaxEnt model was applied to describe the distribution and identify ...

  18. Why Did the Bear Cross the Road? Comparing the Performance of Multiple Resistance Surfaces and Connectivity Modeling Methods

    Directory of Open Access Journals (Sweden)

    Samuel A. Cushman

    2014-12-01

    Full Text Available There have been few assessments of the performance of alternative resistance surfaces, and little is known about how connectivity modeling approaches differ in their ability to predict organism movements. In this paper, we evaluate the performance of four connectivity modeling approaches applied to two resistance surfaces in predicting the locations of highway crossings by American black bears in the northern Rocky Mountains, USA. We found that a resistance surface derived directly from movement data greatly outperformed a resistance surface produced from analysis of genetic differentiation, despite their heuristic similarities. Our analysis also suggested differences in the performance of different connectivity modeling approaches. Factorial least cost paths appeared to slightly outperform other methods on the movement-derived resistance surface, but had very poor performance on the resistance surface obtained from multi-model landscape genetic analysis. Cumulative resistant kernels appeared to offer the best combination of high predictive performance and sensitivity to differences in resistance surface parameterization. Our analysis highlights that even when two resistance surfaces include the same variables and have a high spatial correlation of resistance values, they may perform very differently in predicting animal movement and population connectivity.

  19. Habitat Suitability Modelling of Brown Bear (Ursus arctos in Shimbar Protected Area, Khuzestan Province

    Directory of Open Access Journals (Sweden)

    Z. Obeidavi

    2017-02-01

    Full Text Available Status determination of wildlife habitats is very important in conservation programs and management of wildlife. So, in this study Ursus arctos habitat suitability was modeled using maximum entropy algorithm (MaxEnt in Shimbar protected area. In order to model the habitat suitability, after investigating and resolving the spatial autocorrelation of occurrence records, spatially independent localities were divided into the calibration and evaluation sets and then were combined with 10 environmental variables (VIF<10 selected by MMS software. The performance of predictive models was tested using AUC and jackknife validation test. So, we applied two different thresholds, the LPT threshold and 10% threshold to generate presence/absence map. Also other Jackknife tests applied to measure variables importance. The results showed that predictive model was more efficient than random model (AUC=0.980. In addition, the potential suitable areas cover 20.75% of study area. The MaxEnt model had 88.46% success rate and was statistically significant (P = 0.000. Results of Jackknife showed that ‘plant type’ variable alone contains valuable information for modelling. Our study demonstrated that habitat suitability was successfully predicted by MaxEnt modelling, so this methodology might provide a powerful tool for improving the wildlife habitats information.

  20. Mutations and modeling of the chromatin remodeler CHD8 define an emerging autism etiology

    Directory of Open Access Journals (Sweden)

    Rebecca A Barnard

    2015-12-01

    Full Text Available Autism Spectrum Disorder (ASD is a common neurodevelopmental disorder with a strong but complex genetic component. Recent family based exome-sequencing strategies have identified recurrent de novo mutations at specific genes, providing strong evidence for ASD risk, but also highlighting the extreme genetic heterogeneity of the disorder. However, disruptions in these genes converge on key molecular pathways early in development. In particular, functional enrichment analyses have found that there is a bias towards genes involved in transcriptional regulation, such as chromatin regulators. Here we review recent genetic, animal model, co-expression network, and functional genomics studies relating to the high confidence ASD risk gene, CHD8. CHD8 a chromatin remodeling factor, may serve as a master regulator of a common ASD etiology. Individuals with a CHD8 mutation show an ASD subtype that includes similar physical characteristics, such as macrocephaly and prolonged GI problems including recurrent constipation. Similarly, animal models of CHD8 disruption exhibit enlarged head circumference and reduced gut motility phenotypes. Systems biology approaches suggest CHD8 and other candidate ASD risk genes are enriched during mid-fetal development, which may represent a critical time window in ASD etiology. Transcription profiles from cell and primary tissue models of early development indicate that CHD8 may also positively regulate other candidate ASD risk genes through both direct and indirect means. However continued study is needed to elucidate the mechanism of regulation as well as identify which CHD8 targets are most relevant to ASD risk. Overall, these initial studies suggest the potential for common ASD etiologies and the development of personalized treatments in the future.

  1. Rolling Element Bearing Stiffness Matrix Determination (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Y.; Parker, R.

    2014-01-01

    Current theoretical bearing models differ in their stiffness estimates because of different model assumptions. In this study, a finite element/contact mechanics model is developed for rolling element bearings with the focus of obtaining accurate bearing stiffness for a wide range of bearing types and parameters. A combined surface integral and finite element method is used to solve for the contact mechanics between the rolling elements and races. This model captures the time-dependent characteristics of the bearing contact due to the orbital motion of the rolling elements. A numerical method is developed to determine the full bearing stiffness matrix corresponding to two radial, one axial, and two angular coordinates; the rotation about the shaft axis is free by design. This proposed stiffness determination method is validated against experiments in the literature and compared to existing analytical models and widely used advanced computational methods. The fully-populated stiffness matrix demonstrates the coupling between bearing radial, axial, and tilting bearing deflections.

  2. Compartment model predicts VEGF secretion and investigates the effects of VEGF Trap in tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Stacey D Finley

    2013-07-01

    Full Text Available Angiogenesis, the formation of new blood vessels from existing vasculature, is important in tumor growth and metastasis. A key regulator of angiogenesis is vascular endothelial growth factor (VEGF, which has been targeted in numerous anti-angiogenic therapies aimed at inhibiting tumor angiogenesis. Systems biology approaches, including computational modeling, are useful for understanding this complex biological process and can aid in the development of novel and effective therapeutics that target the VEGF family of proteins and receptors. We have developed a computational model of VEGF transport and kinetics in the tumor-bearing mouse, which includes three compartments: normal tissue, blood, and tumor. The model simulates human tumor xenografts and includes human (VEGF121 and VEGF165 and mouse (VEGF120 and VEGF164 isoforms. The model incorporates molecular interactions between these VEGF isoforms and receptors (VEGFR1 and VEGFR2, as well as co-receptors (NRP1 and NRP2. We also include important soluble factors: soluble VEGFR1 (sFlt-1 and α-2-macroglobulin. The model accounts for transport via macromolecular transendothelial permeability, lymphatic flow, and plasma clearance. We have fit the model to available in vivo experimental data on the plasma concentration of free VEGF Trap and VEGF Trap bound to mouse and human VEGF in order to estimate the rates at which parenchymal cells (myocytes and tumor cells and endothelial cells secrete VEGF. Interestingly, the predicted tumor VEGF secretion rates are significantly lower (0.007 – 0.023 molecules/cell/s, depending on the tumor microenvironment than most reported in vitro measurements (0.03 – 2.65 molecules/cell/s. The optimized model is used to investigate the interstitial and plasma VEGF concentrations and the effect of the VEGF-neutralizing agent, VEGF Trap (aflibercept. This work complements experimental studies performed in mice and provides a framework with which to examine the effects of

  3. A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis

    International Nuclear Information System (INIS)

    Pelz, Joerg OW; Doerfer, Joerg; Hohenberger, Werner; Meyer, Thomas

    2005-01-01

    Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m 2 (n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m 2 (n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals. No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II. The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality

  4. Modeling the ferrochelatase c.315-48C modifier mutation for erythropoietic protoporphyria (EPP in mice

    Directory of Open Access Journals (Sweden)

    Jasmin Barman-Aksözen

    2017-03-01

    Full Text Available Erythropoietic protoporphyria (EPP is caused by deficiency of ferrochelatase (FECH, which incorporates iron into protoporphyrin IX (PPIX to form heme. Excitation of accumulated PPIX by light generates oxygen radicals that evoke excessive pain and, after longer light exposure, cause ulcerations in exposed skin areas of individuals with EPP. Moreover, ∼5% of the patients develop a liver dysfunction as a result of PPIX accumulation. Most patients (∼97% have a severe FECH mutation (Mut in trans to an intronic polymorphism (c.315-48C, which reduces ferrochelatase synthesis by stimulating the use of an aberrant 3′ splice site 63 nt upstream of the normal site for exon 4. In contrast, with the predominant c.315-48T allele, the correct splice site is mostly used, and individuals with a T/Mut genotype do not develop EPP symptoms. Thus, the C allele is a potential target for therapeutic approaches that modify this splicing decision. To provide a model for pre-clinical studies of such approaches, we engineered a mouse containing a partly humanized Fech gene with the c.315-48C polymorphism. F1 hybrids obtained by crossing these mice with another inbred line carrying a severe Fech mutation (named m1Pas show a very strong EPP phenotype that includes elevated PPIX in the blood, enlargement of liver and spleen, anemia, as well as strong pain reactions and skin lesions after a short period of light exposure. In addition to the expected use of the aberrant splice site, the mice also show a strong skipping of the partly humanized exon 3. This will limit the use of this model for certain applications and illustrates that engineering of a hybrid gene may have unforeseeable consequences on its splicing.

  5. BRCA1 and BRCA2 mutation predictions using the BRCAPRO and Myriad models in Korean ovarian cancer patients.

    Science.gov (United States)

    Eoh, Kyung Jin; Park, Ji Soo; Park, Hyung Seok; Lee, Seung-Tae; Han, Jeongwoo; Lee, Jung-Yun; Kim, Sang Wun; Kim, Sunghoon; Kim, Young Tae; Nam, Eun Ji

    2017-04-01

    To evaluate the predictive efficacies including sensitivity and positive predictive value of the genetic risk prediction model BRCAPRO and the Myriad BRCA risk calculator in Korean ovarian cancer patients. Individuals undergoing genetic testing for BRCA mutations from November 2010-August 2016 were recruited from the Department of Obstetrics and Gynecology at a single institute in Korea. The observed BRCA1 and BRCA2 mutation statuses were compared with the predicted carrier probabilities using BRCAPRO and the Myriad BRCA risk calculator. Two hundred thirty-two patients were recruited, of whom 99.1% (230/232) were of Korean ethnicity. Of the 232 individuals, 206 and 26 had ovarian and double primary breast/ovarian cancer, respectively. Thirty-six individuals had a family history of breast/ovarian cancer in first-degree relatives. Fifty-seven patients (24.6%) tested positive for BRCA mutation (41 BRCA1, 16 BRCA2). The mean BRCAPRO and Myriad scores for all patients were 6.4% and 7.7%, respectively. The scores were significantly higher for patients with positive BRCA mutation status (29.0% vs. 6.1%, Pmodels to predict the risk of carrying a BRCA mutation. Both models overestimated the mutation probability in patients with a family history of breast/ovarian cancer (1.55-fold and 1.50-fold, respectively) and underestimated the probability in patients without a family history (both, 0.54-fold). BRCAPRO and Myriad seem to be acceptable risk assessment tools for determining the risk of carrying BRCA mutations in Korean ovarian cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Modeling the kinematics of an autonomous underwater vehicle for range-bearing Simultaneous Localization and Mapping

    CSIR Research Space (South Africa)

    Matsebe, O

    2008-12-01

    Full Text Available realizing more general SLAM solutions and notably in building and using perceptually rich maps as part of a SLAM algorithm. This paper describes the Autonomous Underwater Vehicle (AUV) kinematic and sensor models, it overviews the basic theoretical solution...

  7. Model Test Research on the End Bearing Behavior of the Large-Diameter Cast-in-Place Concrete Pile for Jointed Rock Mass

    Directory of Open Access Journals (Sweden)

    Jingwei Cai

    2016-01-01

    Full Text Available For large-diameter, cast-in-place concrete piles, the end bearing capacity of a single pile is affected by discontinuous surfaces that exist in natural rock masses when the bearing layer of the pile end is located in the rock layer. In order to study the influence of the jointed dip angle on the bearing characteristics of the pile end, the discrete element models are adopted to simulate the mechanical characteristics of the jointed rock masses, and the model tests of the failure mode of the jointed rock masses were also designed. The results of the numerical calculations and modeling tests show that the joints, which have a filtering effect on the internal stress of the bedrock located at the pile end, change the load transferring paths. And the failure mode of the jointed rock foundation also changes as jointed dip angle changes. The rock located at the pile end generally presents a wedge failure mode. In addition, the Q-S curves obtained by model tests show that the ultimate end bearing capacity of a single pile is influenced by the jointed dip angle. The above results provide an important theoretical basis for how to correctly calculate end resistance for a cast-in-place concrete pile.

  8. Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation

    Directory of Open Access Journals (Sweden)

    Ding Chen

    2018-01-01

    Full Text Available X-linked juvenile retinoschisis (XLRS is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1, which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have the exact mutation identified in the patients is extremely crucial, and that the way which genome editing in knock-in animals could be easily transferred to the patients. Here we recruited a family diagnosed with XLRS and identified the causative mutation (RS1, p.Y65X, then a knock-in mouse model harboring this disease-causative mutation was generated via TALEN (transcription activator-like effector nucleases. We found that the b-wave amplitude of the ERG of the RS1-KI mice was significantly decreased. Moreover, we observed that the structure of retina in RS1-KI mice has become disordered, including the disarray of inner nuclear layer and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments of photoreceptor and the loss of outer segments. The novel knock-in mice (RS1-KI harboring patient-specific mutation will be valuable for development of treatment via genome editing mediated gene correction.

  9. A MDP model for breast and ovarian cancer intervention strategies for BRCA1/2 mutation carriers.

    Science.gov (United States)

    Abdollahian, Mehrnaz; Das, Tapas K

    2015-03-01

    Women with BRCA1/2 mutations have higher risk for breast and ovarian cancers. Available intervention actions include prophylactic surgeries and breast screening, which vary significantly in cost, cancer prevention, and in resulting death from other causes. We present a model designed to yield optimal intervention strategies for mutation carriers between the ages of 30 and 65 and any prior intervention history. A Markov decision process (MDP) model is developed that considers yearly state transitions for the mutation carriers and state dependent intervention actions. State is defined as a vector comprising mutation type, health states, prior intervention actions, and age. A discounted value iteration algorithm is used to obtain optimal strategies from the MDP model using both cost and quality-adjusted life years (QALYs) as rewards. The results from MDP model show that for 30-year-old women with BRCA1 mutation and no prior intervention history, the cost-optimal strategy is a combination of prophylactic mastectomy (PM) and prophylactic oophorectomy (PO) at age 30 with no screening afterwards. Whereas, the QALYs-optimal strategy suggests PO at age 30 and PM at age 50 with screening afterwards. For BRCA2 mutation carriers at age 30, the cost-optimal strategy is PO at age 30, PM at age 40, and yearly screening only after age 56. Corresponding QALYs-optimal strategy is PM at age 40 with screening. Strategies for all other ages (31 to 65) are obtained and presented. It is also demonstrated that the cost-optimal strategies offer near maximum survival rate and near minimum cancer incidence rates by age 70, when compared to other ad hoc strategies.

  10. Treatment of dispersed iron-bearing raw materials and modeling of the protection systems against air-pollution

    Directory of Open Access Journals (Sweden)

    Zoran Anđić

    2016-12-01

    Full Text Available Based on the analysis of the non-standard iron-bearing raw materials treatment process and the results of real composition measurements of the flue gas, the study of hazards by identification of harmful substances that occur in the accident, as well as the modeling of the system of protection against air-pollution due to the cancellation of work the bag filter was carried out. Applying the model (Aloha software package provides an overview of possible developments of events and zones of propagation of the precipitated particulate matter through the share of cadmium (Cd in them. In the case of malfunction of filter system, emissions of particulate matter enormously exceed the permitted values. In the conditions of the simulated accident, particle velocity of flue gases was amounted E≈738mg/s or 2657g/h of dust. The propagation of the precipitated particulate matter in the lower layer of the atmosphere, downwind, given trough the share of Cd in them, is 100m from the source of pollution for the characteristic density of 5mg/m2×day and 140m for the characteristic density of 2mg/m2×day, in the stable state of the atmosphere, i.e. 870m and 1100m, respectively, in the neutral state of the atmosphere.

  11. A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21

    International Nuclear Information System (INIS)

    Nagata, Noriyo; Iwasaki, Takuya; Ami, Yasushi; Sato, Yuko; Hatano, Ikuyoshi; Harashima, Ayako; Suzaki, Yuriko; Yoshii, Takao; Hashikawa, Tsutomu; Sata, Tetsutaro; Horiuchi, Yoshinobu; Koike, Satoshi; Kurata, Takeshi; Nomoto, Akio

    2004-01-01

    Transgenic mice bearing the human poliovirus receptor (TgPVR) are less susceptible to oral inoculation, although they are susceptible to parenteral inoculation. We investigated the susceptibility of TgPVR 21 line [Arch. Virol. 130 (1994) 351] to poliovirus through various mucosal routes. Intranasal inoculation of a neurovirulent Mahoney strain (OM1) caused flaccid paralysis with viral replication in the central nervous system at a dose of 10 6 cell culture infectious dose (CCID 50 ), in contrast, no paralysis following oral or intragastric inoculation of the same dose. Intranasal inoculation of a vaccine strain, Sabin 1, at 10 6 CCID 50 , resulted in no paralysis. Initial replication of poliovirus in the nasal cavity was confirmed by virus isolation and detection of negative-stranded replicative intermediates by RT-PCR and viral antigens using a high-sensitive immunohistochemistry and genome/transcripts by in situ hybridization. Poliovirus-specific IgG antibodies were elevated in the sera of surviving TgPVR21. This model can be used as a mucosal infection model and for differentiation of neurovirulent and attenuated poliovirus strains

  12. Coevolutionary modeling of protein sequences: Predicting structure, function, and mutational landscapes

    Science.gov (United States)

    Weigt, Martin

    Over the last years, biological research has been revolutionized by experimental high-throughput techniques, in particular by next-generation sequencing technology. Unprecedented amounts of data are accumulating, and there is a growing request for computational methods unveiling the information hidden in raw data, thereby increasing our understanding of complex biological systems. Statistical-physics models based on the maximum-entropy principle have, in the last few years, played an important role in this context. To give a specific example, proteins and many non-coding RNA show a remarkable degree of structural and functional conservation in the course of evolution, despite a large variability in amino acid sequences. We have developed a statistical-mechanics inspired inference approach - called Direct-Coupling Analysis - to link this sequence variability (easy to observe in sequence alignments, which are available in public sequence databases) to bio-molecular structure and function. In my presentation I will show, how this methodology can be used (i) to infer contacts between residues and thus to guide tertiary and quaternary protein structure prediction and RNA structure prediction, (ii) to discriminate interacting from non-interacting protein families, and thus to infer conserved protein-protein interaction networks, and (iii) to reconstruct mutational landscapes and thus to predict the phenotypic effect of mutations. References [1] M. Figliuzzi, H. Jacquier, A. Schug, O. Tenaillon and M. Weigt ''Coevolutionary landscape inference and the context-dependence of mutations in beta-lactamase TEM-1'', Mol. Biol. Evol. (2015), doi: 10.1093/molbev/msv211 [2] E. De Leonardis, B. Lutz, S. Ratz, S. Cocco, R. Monasson, A. Schug, M. Weigt ''Direct-Coupling Analysis of nucleotide coevolution facilitates RNA secondary and tertiary structure prediction'', Nucleic Acids Research (2015), doi: 10.1093/nar/gkv932 [3] F. Morcos, A. Pagnani, B. Lunt, A. Bertolino, D. Marks, C

  13. Modeling and Simulation on Errors of Feed Unit by Considering Change of Force Bearing Point

    Directory of Open Access Journals (Sweden)

    Zhang Wei

    2017-01-01

    Full Text Available The linear feed unit is a type of precision linear motion component that is widely used in computer numerical control (CNC machine tools. The contact stiffness and error influences the performance of the feed unit directly. Thus, investigating contact stiffness and error is important in optimizing the design and improving the performance of the linear feed unit. In this study, the contact mechanics and the deformation of the roller between the roller and rail are analyzed. Calculation model of the contact stiffness and error based on the Hertz theory and multi-body kinematics are established and the change of the contact angle is also considered. Errors and the contact stiffness curve of five directions and the changes of the slope of the stiffness curve after the load increases to a certain size are obtained. The Motion precision errors of The roller linear feed unit are analyzed. The effectiveness of the proposed models on contact stiffness and error is verified through simulation on a specialized test system of the linear feed unit

  14. Improvement of journal bearing operation at heavy misalignment using bearing flexibility and compliant liners

    OpenAIRE

    Thomsen, Kim; Klit, Peder

    2012-01-01

    A flexure journal bearing design is proposed that will improve operational behaviour of a journal bearing at pronounced misalignment. Using a thermoelastohydrodynamic model, it is shown that the proposed flexure journal bearing has vastly increased the hydrodynamic performance compared to the stiff bearing when misaligned. The hydrodynamic performance is evaluated on lubricant film thickness, pressure and temperature. Furthermore, the influence of a compliant bearing liner is investigated and...

  15. Improvement of journal bearing operation at heavy misalignment using bearing flexibility and compliant liners

    DEFF Research Database (Denmark)

    Thomsen, Kim; Klit, Peder

    2012-01-01

    A flexure journal bearing design is proposed that will improve operational behaviour of a journal bearing at pronounced misalignment. Using a thermoelastohydrodynamic model, it is shown that the proposed flexure journal bearing has vastly increased the hydrodynamic performance compared to the stiff...... bearing when misaligned. The hydrodynamic performance is evaluated on lubricant film thickness, pressure and temperature. Furthermore, the influence of a compliant bearing liner is investigated and it is found that it increases the hydrodynamic performance when applied to a stiff bearing, whereas...... the liner has practically no influence on the flexure journal bearing's performance....

  16. Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy

    OpenAIRE

    Tardiff, Jil C.; Hewett, Timothy E.; Palmer, Bradley M.; Olsson, Charlotte; Factor, Stephen M.; Moore, Russell L.; Robbins, Jeffrey; Leinwand, Leslie A.

    1999-01-01

    Multiple mutations in cardiac troponin T (cTnT) can cause familial hypertrophic cardiomyopathy (FHC). Patients with cTnT mutations generally exhibit mild or no ventricular hypertrophy, yet demonstrate a high frequency of early sudden death. To understand the functional basis of these phenotypes, we created transgenic mouse lines expressing 30%, 67%, and 92% of their total cTnT as a missense (R92Q) allele analogous to one found in FHC. Similar to a mouse FHC model expressing a truncated cTnT p...

  17. Stable isotopes to detect food-conditioned bears and to evaluate human-bear management

    Science.gov (United States)

    Hopkins, John B.; Koch, Paul L.; Schwartz, Charles C.; Ferguson, Jake M.; Greenleaf, Schuyler S.; Kalinowski, Steven T.

    2012-01-01

    We used genetic and stable isotope analysis of hair from free-ranging black bears (Ursus americanus) in Yosemite National Park, California, USA to: 1) identify bears that consume human food, 2) estimate the diets of these bears, and 3) evaluate the Yosemite human–bear management program. Specifically, we analyzed the isotopic composition of hair from bears known a priori to be food-conditioned or non-food-conditioned and used these data to predict whether bears with an unknown management status were food-conditioned (FC) or non-food-conditioned (NFC). We used a stable isotope mixing model to estimate the proportional contribution of natural foods (plants and animals) versus human food in the diets of FC bears. We then used results from both analyses to evaluate proactive (population-level) and reactive (individual-level) human–bear management, and discussed new metrics to evaluate the overall human–bear management program in Yosemite. Our results indicated that 19 out of 145 (13%) unknown bears sampled from 2005 to 2007 were food-conditioned. The proportion of human food in the diets of known FC bears likely declined from 2001–2003 to 2005–2007, suggesting proactive management was successful in reducing the amount of human food available to bears. In contrast, reactive management was not successful in changing the management status of known FC bears to NFC bears, or in reducing the contribution of human food to the diets of FC bears. Nine known FC bears were recaptured on 14 occasions from 2001 to 2007; all bears were classified as FC during subsequent recaptures, and human–bear management did not reduce the amount of human food in the diets of FC bears. Based on our results, we suggest Yosemite continue implementing proactive human–bear management, reevaluate reactive management, and consider removing problem bears (those involved in repeated bear incidents) from the population.

  18. Health effects from long-range transported contaminants in Arctic top predators: An integrated review based on studies of polar bears and relevant model species.

    Science.gov (United States)

    Sonne, Christian

    2010-07-01

    weight, respectively. Furthermore, PFC concentrations, at which population effect levels could occur, are likely to be reached around year 2012 for the East Greenland polar bear subpopulation if current increasing temporal trends continue. Such proposed reproductive population effects were supported by physiological based pharmacokinetic (PBPK) modelling of critical body residues (CBR) with risk quotients >or=1 for SigmaPCB, dieldrin, SigmaPFC and SigmaOHC (organohalogen contaminant). The estimated daily TEQ for East Greenland polar bears and East Greenland sledge dogs were 32-281-folds above WHO SigmaTEQ guidelines for humans. Compared to human tolerable daily intake (TDI), these were exceeded for PCBs, dieldrin, chlordanes and SigmaHCH in East Greenland polar bears. Comparisons like these should be done with caution, but together with the CBR modelling and T-score estimations, these were the only available tools for polar bear risk evaluation. In conclusion, polar bears seem to be susceptible to contaminant induced stress that may have an overall sub-clinical impact on their health and population status via impacts on their immune and reproductive systems. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish model

    NARCIS (Netherlands)

    Yen, J.; White, R.M.; Wedge, D.C.; Van Loo, P.; De Ridder, J.; Capper, A.; Richardson, J.; Jones, D.; Raine, K.; Watson, I.R.

    2013-01-01

    Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and

  20. Computational design of model Re/Ru bearing Ni-base superalloys

    Directory of Open Access Journals (Sweden)

    Vamsi K.V.

    2014-01-01

    Full Text Available It is well established that Re and Ru additions to Ni-base superalloys result in improved creep performance and phase stability. However, the role of Re and Ru and their synergetic effects are not well understood, and the first step in understanding these effects is to design alloys with controlled microstructural parameters. A computational approach was undertaken in the present work for designing model alloys with varying levels of Re and Ru. Thermodynamic and first principles calculations were employed complimentarily to design a set of alloys with varying Re and Ru levels, but which were constrained by constant microstructural parameters, i.e., phase fractions and lattice misfit across the alloys. Three ternary/quaternary alloys of type Ni-Al-xRe-yRu were thus designed. These compositions were subsequently cast, homogenized and aged. Experimental results suggest that while the measured volume fraction matches the predicted value in the Ru containing alloy, volume fraction is significantly higher than the designed value in the Re containing alloys. This is possibly due to errors in the thermodynamic database used to predict phase fraction and composition. These errors are also reflected in the mismatch between predicted and measured values of misfit.

  1. Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic.

    Science.gov (United States)

    Dietz, Rune; Gustavson, Kim; Sonne, Christian; Desforges, Jean-Pierre; Rigét, Frank F; Pavlova, Viola; McKinney, Melissa A; Letcher, Robert J

    2015-07-01

    Polar bears (Ursus maritimus) consume large quantities of seal blubber and other high trophic marine mammals and consequently have some of the highest tissue concentrations of organohalogen contaminants (OHCs) among Arctic biota. In the present paper we carried out a risk quotient (RQ) evaluation on OHC-exposed polar bears harvested from 1999 to 2008 and from 11 circumpolar subpopulations spanning from Alaska to Svalbard in order to evaluate the risk of OHC-mediated reproductive effects (embryotoxicity, teratogenicity), immunotoxicity and carcinogenicity (genotoxicity). This RQ evaluation was based on the Critical Body Residue (CBR) concept and a Physiologically-Based Pharmacokinetic Modelling (PBPK) approach using OHC concentrations measured in polar bear adipose or liver tissue. The range of OHC concentrations within polar bear populations were as follows for adipose, sum polychlorinated biphenyls ∑PCBs (1797-10,537 ng/g lw), sum methylsulphone-PCB ∑MeSO2-PCBs (110-672 ng/g lw), sum chlordanes ∑CHLs (765-3477 ng/g lw), α-hexachlorocyclohexane α-HCH (8.5-91.3 ng/g lw), β-hexachlorocyclohexane β-HCH (65.5-542 ng/g lw), sum chlorbenzenes ∑ClBzs (145-304 ng/g lw), dichlorodiphenyltrichloroethane ∑DDTs (31.5-206 ng/g lw), dieldrin (69-249 ng/g lw), polybrominated diphenyl ethers ∑PBDEs (4.6-78.4 ng/g lw). For liver, the perfluorooctanesulfonic acid (PFOS) concentrations ranged from 231-2792 ng/g ww. The total additive RQ from all OHCs ranged from 4.3 in Alaska to 28.6 in East Greenland bears for effects on reproduction, immune health and carcinogenicity, highlighting the important result that the toxic effect threshold (i.e. RQ>1) was exceeded for all polar bear populations assessed. PCBs were the main contributors for all three effect categories, contributing from 70.6% to 94.3% of the total risk and a RQ between 3.8-22.5. ∑MeSO2-PCBs were the second highest effect contributor for reproductive and immunological effects (0.17polar bears. We therefore

  2. NF-kappa B binding mechanism: a nuclear magnetic resonance and modeling study of a GGG --> CTC mutation.

    Science.gov (United States)

    Tisné, C; Hartmann, B; Delepierre, M

    1999-03-30

    We present the solution structure of the nonpalindromic 16 bp DNA 5'd(CTGCTCACTTTCCAGG)3'. 5'd(CCTGGAAAGTGAGCAG)3' containing a mutated kappaB site for which the mutation of a highly conserved GGG tract of the native kappaB HIV-1 site to CTC abolishes NF-kappaB binding. 1H and 31P NMR spectroscopies have been used together with molecular modeling to determine the fine structure of the duplex. NMR data show evidence for a BI-BII equilibrium of the CpA.TpG steps at the 3'-end of the oligomer. Models for the extreme conformations reached by the mutated duplex (denoted 16M) are proposed in agreement with the NMR data. Since the distribution of BII sites is changed in the mutated duplex compared to that of the native duplex (denoted 16N), large differences are induced in the intrinsic structural properties of both duplexes. In particular, in BII structures, 16M shows a kink located at the 3'-end of the duplex, and in contrast, 16N exhibits an intrinsic global curvature toward the major groove. Whereas 16N can reach a conformation very favorable for the interaction with NF-kappaB, 16M cannot mimic such a conformation and, moreover, its deeper and narrower major groove could hinder the DNA-protein interactions.

  3. High-resolution mutational profiling suggests the genetic validity of glioblastoma patient-derived pre-clinical models.

    Directory of Open Access Journals (Sweden)

    Shawn E Yost

    Full Text Available Recent advances in the ability to efficiently characterize tumor genomes is enabling targeted drug development, which requires rigorous biomarker-based patient selection to increase effectiveness. Consequently, representative DNA biomarkers become equally important in pre-clinical studies. However, it is still unclear how well these markers are maintained between the primary tumor and the patient-derived tumor models. Here, we report the comprehensive identification of somatic coding mutations and copy number aberrations in four glioblastoma (GBM primary tumors and their matched pre-clinical models: serum-free neurospheres, adherent cell cultures, and mouse xenografts. We developed innovative methods to improve the data quality and allow a strict comparison of matched tumor samples. Our analysis identifies known GBM mutations altering PTEN and TP53 genes, and new actionable mutations such as the loss of PIK3R1, and reveals clear patient-to-patient differences. In contrast, for each patient, we do not observe any significant remodeling of the mutational profile between primary to model tumors and the few discrepancies can be attributed to stochastic errors or differences in sample purity. Similarly, we observe ∼96% primary-to-model concordance in copy number calls in the high-cellularity samples. In contrast to previous reports based on gene expression profiles, we do not observe significant differences at the DNA level between in vitro compared to in vivo models. This study suggests, at a remarkable resolution, the genome-wide conservation of a patient's tumor genetics in various pre-clinical models, and therefore supports their use for the development and testing of personalized targeted therapies.

  4. Journal and Wave Bearing Impedance Calculation Software

    Science.gov (United States)

    Hanford, Amanda; Campbell, Robert

    2012-01-01

    The wave bearing software suite is a MALTA application that computes bearing properties for user-specified wave bearing conditions, as well as plain journal bearings. Wave bearings are fluid film journal bearings with multi-lobed wave patterns around the circumference of the bearing surface. In this software suite, the dynamic coefficients are outputted in a way for easy implementation in a finite element model used in rotor dynamics analysis. The software has a graphical user interface (GUI) for inputting bearing geometry parameters, and uses MATLAB s structure interface for ease of interpreting data. This innovation was developed to provide the stiffness and damping components of wave bearing impedances. The computational method for computing bearing coefficients was originally designed for plain journal bearings and tilting pad bearings. Modifications to include a wave bearing profile consisted of changing the film thickness profile given by an equation, and writing an algorithm to locate the integration limits for each fluid region. Careful consideration was needed to implement the correct integration limits while computing the dynamic coefficients, depending on the form of the input/output variables specified in the algorithm.

  5. A two level mutation-selection model of cultural evolution and diversity.

    Science.gov (United States)

    Salazar-Ciudad, Isaac

    2010-11-21

    Cultural evolution is a complex process that can happen at several levels. At the level of individuals in a population, each human bears a set of cultural traits that he or she can transmit to its offspring (vertical transmission) or to other members of his or her society (horizontal transmission). The relative frequency of a cultural trait in a population or society can thus increase or decrease with the relative reproductive success of its bearers (individual's level) or the relative success of transmission (called the idea's level). This article presents a mathematical model on the interplay between these two levels. The first aim of this article is to explore when cultural evolution is driven by the idea's level, when it is driven by the individual's level and when it is driven by both. These three possibilities are explored in relation to (a) the amount of interchange of cultural traits between individuals, (b) the selective pressure acting on individuals, (c) the rate of production of new cultural traits, (d) the individual's capacity to remember cultural traits and to the population size. The aim is to explore the conditions in which cultural evolution does not lead to a better adaptation of individuals to the environment. This is to contrast the spread of fitness-enhancing ideas, which make individual bearers better adapted to the environment, to the spread of "selfish" ideas, which spread well simply because they are easy to remember but do not help their individual bearers (and may even hurt them). At the same time this article explores in which conditions the adaptation of individuals is maximal. The second aim is to explore how these factors affect cultural diversity, or the amount of different cultural traits in a population. This study suggests that a larger interchange of cultural traits between populations could lead to cultural evolution not improving the adaptation of individuals to their environment and to a decrease of cultural diversity

  6. MODELING AND ANALYSIS OF DYNAMICS IN BEARING SYSTEM OF DRILLING, MILLING AND BORING MACHINE WITH MONO-COLUMN

    OpenAIRE

    Yu. V. Vasilevich; S. S. Dovnar; A. S. Truskovsky; I. I. Shumsky

    2015-01-01

     FEM-analysis of dynamics in the bearing system of a heavy-duty machine tool has been carried out in the paper. This is a prospective variant for a large-size multi-purpose machine tool with a horizontal sliding ram. A saddle and a ram are moving vertically along a subtle mono-column. A rigid double-column is used in the existing analog machine tool. A static, modal and harmonic analysis of the bearing system with the mono-column has been made in the paper. It has been done with the help of F...

  7. Performance of Lynch syndrome predictive models in quantifying the likelihood of germline mutations in patients with abnormal MLH1 immunoexpression.

    Science.gov (United States)

    Cabreira, Verónica; Pinto, Carla; Pinheiro, Manuela; Lopes, Paula; Peixoto, Ana; Santos, Catarina; Veiga, Isabel; Rocha, Patrícia; Pinto, Pedro; Henrique, Rui; Teixeira, Manuel R

    2017-01-01

    Lynch syndrome (LS) accounts for up to 4 % of all colorectal cancers (CRC). Detection of a pathogenic germline mutation in one of the mismatch repair genes is the definitive criterion for LS diagnosis, but it is time-consuming and expensive. Immunohistochemistry is the most sensitive prescreening test and its predictive value is very high for loss of expression of MSH2, MSH6, and (isolated) PMS2, but not for MLH1. We evaluated if LS predictive models have a role to improve the molecular testing algorithm in this specific setting by studying 38 individuals referred for molecular testing and who were subsequently shown to have loss of MLH1 immunoexpression in their tumors. For each proband we calculated a risk score, which represents the probability that the patient with CRC carries a pathogenic MLH1 germline mutation, using the PREMM 1,2,6 and MMRpro predictive models. Of the 38 individuals, 18.4 % had a pathogenic MLH1 germline mutation. MMRpro performed better for the purpose of this study, presenting a AUC of 0.83 (95 % CI 0.67-0.9; P < 0.001) compared with a AUC of 0.68 (95 % CI 0.51-0.82, P = 0.09) for PREMM 1,2,6 . Considering a threshold of 5 %, MMRpro would eliminate unnecessary germline mutation analysis in a significant proportion of cases while keeping very high sensitivity. We conclude that MMRpro is useful to correctly predict who should be screened for a germline MLH1 gene mutation and propose an algorithm to improve the cost-effectiveness of LS diagnosis.

  8. Beta-Binomial Model for the Detection of Rare Mutations in Pooled Next-Generation Sequencing Experiments.

    Science.gov (United States)

    Jakaitiene, Audrone; Avino, Mariano; Guarracino, Mario Rosario

    2017-04-01

    Against diminishing costs, next-generation sequencing (NGS) still remains expensive for studies with a large number of individuals. As cost saving, sequencing genome of pools containing multiple samples might be used. Currently, there are many software available for the detection of single-nucleotide polymorphisms (SNPs). Sensitivity and specificity depend on the model used and data analyzed, indicating that all software have space for improvement. We use beta-binomial model to detect rare mutations in untagged pooled NGS experiments. We propose a multireference framework for pooled data with ability being specific up to two patients affected by neuromuscular disorders (NMD). We assessed the results comparing with The Genome Analysis Toolkit (GATK), CRISP, SNVer, and FreeBayes. Our results show that the multireference approach applying beta-binomial model is accurate in predicting rare mutations at 0.01 fraction. Finally, we explored the concordance of mutations between the model and software, checking their involvement in any NMD-related gene. We detected seven novel SNPs, for which the functional analysis produced enriched terms related to locomotion and musculature.

  9. A biogeography-based optimization algorithm with mutation strategies for model parameter estimation of solar and fuel cells

    International Nuclear Information System (INIS)

    Niu, Qun; Zhang, Letian; Li, Kang

    2014-01-01

    Highlights: • Solar cell and PEM fuel cell parameter estimations are investigated in the paper. • A new biogeography-based method (BBO-M) is proposed for cell parameter estimations. • In BBO-M, two mutation operators are designed to enhance optimization performance. • BBO-M provides a competitive alternative in cell parameter estimation problems. - Abstract: Mathematical models are useful tools for simulation, evaluation, optimal operation and control of solar cells and proton exchange membrane fuel cells (PEMFCs). To identify the model parameters of these two type of cells efficiently, a biogeography-based optimization algorithm with mutation strategies (BBO-M) is proposed. The BBO-M uses the structure of biogeography-based optimization algorithm (BBO), and both the mutation motivated from the differential evolution (DE) algorithm and the chaos theory are incorporated into the BBO structure for improving the global searching capability of the algorithm. Numerical experiments have been conducted on ten benchmark functions with 50 dimensions, and the results show that BBO-M can produce solutions of high quality and has fast convergence rate. Then, the proposed BBO-M is applied to the model parameter estimation of the two type of cells. The experimental results clearly demonstrate the power of the proposed BBO-M in estimating model parameters of both solar and fuel cells

  10. State Space Formulation of Nonlinear Vibration Responses Collected from a Dynamic Rotor-Bearing System: An Extension of Bearing Diagnostics to Bearing Prognostics

    Directory of Open Access Journals (Sweden)

    Peter W. Tse

    2017-02-01

    Full Text Available Bearings are widely used in various industries to support rotating shafts. Their failures accelerate failures of other adjacent components and may cause unexpected machine breakdowns. In recent years, nonlinear vibration responses collected from a dynamic rotor-bearing system have been widely analyzed for bearing diagnostics. Numerous methods have been proposed to identify different bearing faults. However, these methods are unable to predict the future health conditions of bearings. To extend bearing diagnostics to bearing prognostics, this paper reports the design of a state space formulation of nonlinear vibration responses collected from a dynamic rotor-bearing system in order to intelligently predict bearing remaining useful life (RUL. Firstly, analyses of nonlinear vibration responses were conducted to construct a bearing health indicator (BHI so as to assess the current bearing health condition. Secondly, a state space model of the BHI was developed to mathematically track the health evolution of the BHI. Thirdly, unscented particle filtering was used to predict bearing RUL. Lastly, a new bearing acceleration life testing setup was designed to collect natural bearing degradation data, which were used to validate the effectiveness of the proposed bearing prognostic method. Results show that the prediction accuracy of the proposed bearing prognostic method is promising and the proposed bearing prognostic method is able to reflect future bearing health conditions.

  11. Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism

    Directory of Open Access Journals (Sweden)

    Camilla Ceccatelli Berti

    2015-04-01

    Full Text Available Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA, namely PKAN and CoPAN. PKAN are defined by mutations in PANK2, encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthase COASY have been recently reported as the second inborn error of CoA synthesis leading to CoPAN. As reported previously, yeast cells expressing the pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.

  12. On the Incorporation of Friction Into a Simultaneously Coupled Time Domain Model of a Rigid Rotor Supported by Air Foil Bearings

    DEFF Research Database (Denmark)

    von Osmanski, Alexander Sebastian; Larsen, Jon Steffen; Santos, Ilmar

    2017-01-01

    Despite decades of research, the dynamics of air foil bearings (AFBs) are not yet fully captured by any model,suggesting that the fundamental mechanisms of the AFB and their relative merits are not yet fully understood. The recent years have seen promising results from nonlinear time domain models......, allowing the dynamic pressure–compliance interaction and the unsteady terms of the compressible Reynolds equation to be considered. By including the simple elastic foundation model (SEFM) in a fully coupled simultaneous time integration, the dynamics of a rotor supported by industrial AFBs have previously...

  13. Bifurcation Analysis of a Chemostat Model of Plasmid-Bearing and Plasmid-Free Competition with Pulsed Input

    Directory of Open Access Journals (Sweden)

    Zhong Zhao

    2014-01-01

    to the stability of the boundary periodic solution. By use of standard techniques of bifurcation theory, the periodic oscillations in substrate, plasmid-bearing, and plasmid-free organisms are shown when some conditions are satisfied. Our results can be applied to control bioreactor aimed at producing commercial producers through genetically altered organisms.

  14. Modeling cystic fibrosis disease progression in patients with the rare CFTR mutation P67L.

    Science.gov (United States)

    MacKenzie, Isobel E R; Paquette, Valerie; Gosse, Frances; George, Sheenagh; Chappe, Frederic; Chappe, Valerie

    2017-05-01

    The progression of cystic fibrosis (CF) in patients with the rare mutation P67L was examined to determine if it induced a milder form of CF compared to the common severe ΔF508 mutation. Parameters of lung function, level of bacterial infection, nutritional status and hospitalization were used to represent CF progression. Age at diagnosis and pancreatic status were used to assess CF presentation. Analysis of data from the CF Canada Registry collected over a 15-year period included 266 ΔF508/ΔF508 homozygote patients from CF clinics in Atlantic Canada and 26 compound heterozygote patients with the rare P67L mutation from clinics across Canada. Late age at diagnosis, high incidence of pancreatic sufficiency, maintained Body Mass Index (BMI) with age, delayed life-threatening bacterial infection, and fewer days in hospital were observed for P67L heterozygote patients included in this study. Although the decline of lung function did not differ from ΔF508 homozygotes, the fact that a greater proportion of P67L heterozygotes live to an older age suggests that lung function is not the primary factor determining CF progression for P67L heterozygote patients. The P67L mutation is associated with a mild disease, even when combined with the severe ΔF508 mutation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  15. Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in pleuropulmonary blastoma / DICER1 syndrome: a unique variant of the two-hit tumor suppression model [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Mark Brenneman

    2018-01-01

    Full Text Available Pleuropulmonary blastoma (PPB is the most frequent pediatric lung tumor and often the first indication of a pleiotropic cancer predisposition, DICER1 syndrome, comprising a range of other individually rare, benign and malignant tumors of childhood and early adulthood. The genetics of DICER1-associated tumorigenesis are unusual in that tumors typically bear neomorphic missense mutations at one of five specific “hotspot” codons within the RNase IIIb domain of DICER 1, combined with complete loss of function (LOF in the other allele. We analyzed a cohort of 124 PPB children for predisposing DICER1 mutations and sought correlations with clinical phenotypes. Over 70% have inherited or de novo germline LOF mutations, most of which truncate the DICER1 open reading frame. We identified a minority of patients who have no germline mutation, but are instead mosaic for predisposing DICER1 mutations. Mosaicism for RNase IIIb domain hotspot mutations defines a special category of DICER1 syndrome patients, clinically distinguished from those with germline or mosaic LOF mutations by earlier onsets and numerous discrete foci of neoplastic disease involving multiple syndromic organ sites. A final category of PBB patients lack predisposing germline or mosaic mutations and have sporadic (rather than syndromic disease limited to a single PPB tumor bearing tumor-specific RNase IIIb and LOF mutations. We propose that acquisition of a neomorphic RNase IIIb domain mutation is the rate limiting event in DICER1-associated tumorigenesis, and that distinct clinical phenotypes associated with mutational categories reflect the temporal order in which LOF and RNase IIIb domain mutations are acquired during development.

  16. A new modal-based approach for modelling the bump foil structure in the simultaneous solution of foil-air bearing rotor dynamic problems

    Science.gov (United States)

    Bin Hassan, M. F.; Bonello, P.

    2017-05-01

    Recently-proposed techniques for the simultaneous solution of foil-air bearing (FAB) rotor dynamic problems have been limited to a simple bump foil model in which the individual bumps were modelled as independent spring-damper (ISD) subsystems. The present paper addresses this limitation by introducing a modal model of the bump foil structure into the simultaneous solution scheme. The dynamics of the corrugated bump foil structure are first studied using the finite element (FE) technique. This study is experimentally validated using a purpose-made corrugated foil structure. Based on the findings of this study, it is proposed that the dynamics of the full foil structure, including bump interaction and foil inertia, can be represented by a modal model comprising a limited number of modes. This full foil structure modal model (FFSMM) is then adapted into the rotordynamic FAB problem solution scheme, instead of the ISD model. Preliminary results using the FFSMM under static and unbalance excitation conditions are proven to be reliable by comparison against the corresponding ISD foil model results and by cross-correlating different methods for computing the deflection of the full foil structure. The rotor-bearing model is also validated against experimental and theoretical results in the literature.

  17. A motor with superconducting magnetic bearings

    International Nuclear Information System (INIS)

    Gladun, A.; Stoye, P.; Verges, P.; Gawalek, W.; Habisreuther, T.; Goernert, P.

    1993-01-01

    Superconducting bearings may be one of the most promising near term applications of HTSC. For use at liquid nitrogen temperature and below, they offer the advantage of lower energy consumption and higher reliability. Different bearing configurations have been proposed. But in order to substitute for conventional bearings a further increase in the critical current density of the superconductor and improved bearing concepts are necessary. For this it is necessary to take into account the peculiarities of the interaction between permanent magnets and bulk superconductors. As a contribution to this programme we present the model of a motor with superconducting magnetic bearings. (orig.)

  18. Ball Bearing Analysis with the ORBIS Tool

    Science.gov (United States)

    Halpin, Jacob D.

    2016-01-01

    Ball bearing design is critical to the success of aerospace mechanisms. Key bearing performance parameters, such as load capability, stiffness, torque, and life all depend on accurate determination of the internal load distribution. Hence, a good analytical bearing tool that provides both comprehensive capabilities and reliable results becomes a significant asset to the engineer. This paper introduces the ORBIS bearing tool. A discussion of key modeling assumptions and a technical overview is provided. Numerous validation studies and case studies using the ORBIS tool are presented. All results suggest the ORBIS code closely correlates to predictions on bearing internal load distributions, stiffness, deflection and stresses.

  19. Predicting anti-tumor effect of deoxypodophyllotoxin in NCI-H460 tumor-bearing mice based on in vitro pharmacodynamics and physiologically based pharmacokinetic-pharmacodynamic model.

    Science.gov (United States)

    Chen, Yang; Zhao, Kaijing; Liu, Fei; Li, Ying; Zhong, Zeyu; Hong, Shijin; Liu, Xiaodong; Liu, Li

    2018-04-04

    Anti-tumor evaluation in tumor-bearing mouse is time- and energy-consuming. We aimed to investigate whether in vivo anti-tumor efficacy could be predicted based on in vitro pharmacodynamics using deoxypodophyllotoxin (DPT), a developing anti-tumor candidate, as a model compound. Proliferation kinetics of monolayer cultivated NCI-H460 cells under various DPT concentrations was quantitatively investigated accompanied by calibration curves. Koch's two-phase natural growth model combined with sigmoid Emax model, i.e. dM/dt=2λ 0 λ 1 M/(λ 1 +2λ 0 M)-EmaxC γ /(EC 50 γ +C γ )·M, was introduced to describe cell proliferation (M) against time under DPT treatment (C). Estimated in vitro pharmacodynamic parameters were: EC 50 , 8.97 nM; Emax, 0.820 day -1 and γ, 7.13. A physiologically based pharmacokinetic (PBPK) model including tumor compartment was introduced, which could predict DPT disposition in plasma, tumor tissue and main normal tissues of NCI-H460 tumor-bearing mice following single dose. In vivo pharmacodynamic model and parameters were assumed the same as in vitro ones, and linked with simulated tumor pharmacokinetic profiles by PBPK model, to build a physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) model. After estimating natural growth parameters (λ 0 and λ 1 ), we desirably predicted the tumor growth in NCI-H460 tumor-bearing mice during multi-dose DPT treatment, both in this study and literature, by the PBPK-PD model. The model was further successfully applied to predict tumor growth in SGC-7901 tumor-bearing mice. These data indicated that in vivo anti-tumor efficacy might be predicted based on in vitro cytotoxic assays via PBPK-PD model approach. The approach was demonstrated reasonable and applicable, which might facilitate and accelerate anti-cancer candidate screening and dose regimen design in drug discovery process. The American Society for Pharmacology and Experimental Therapeutics.

  20. Deformation Analysis of Fixed Bearing Inclined Plane Thrust Bearing

    Directory of Open Access Journals (Sweden)

    LI Yong--hai

    2017-02-01

    Full Text Available According to the theory of lubrication,Numerical simulation of the deformation of the thrust bearing of the fixed inclined plane was carried out,by finite element numerical analysis method and using the ANSYS software. The mathematical model of the oil film shape control equations about of the deformation and bearing is established. Analytical result showed that the force caused the tile surface generating concave deformation,and convex deformation increased with the height and the size of the load and bearing;Tile surface temperature generated convex deformation and increased with the height and the size of the temperature of bearing bush;The actual deformation of the tile surface is the superposition of the force and the thermal deformation. This conclusion can provide reference for the design and the application of thrust bearing,to reduce the tile surface,which is not conducive to the carrying capacity of the concave deformation.

  1. Dynamic analysis of centrifugal machines rotors supported on ball bearings by combined application of 3D and beam finite element models

    Science.gov (United States)

    Pavlenko, I. V.; Simonovskiy, V. I.; Demianenko, M. M.

    2017-08-01

    This research paper is aimed to investigating rotor dynamics of multistage centrifugal machines with ball bearings by using the computer programs “Critical frequencies of the rotor” and “Forced oscillations of the rotor,” which are implemented the mathematical model based on the use of beam finite elements. Free and forces oscillations of the rotor for the multistage centrifugal oil pump NPS 200-700 are observed by taking into account the analytical dependence of bearing stiffness on rotor speed, which is previously defined on the basis of results’ approximation for the numerical simulation in ANSYS by applying 3D finite elements. The calculations found that characteristic and constrained oscillations of rotor and corresponded to them forms of vibrations, as well as the form of constrained oscillation on the actual frequency for acceptable residual unbalance are determined.

  2. Passive magnetic bearing configurations

    Science.gov (United States)

    Post, Richard F [Walnut Creek, CA

    2011-01-25

    A journal bearing provides vertical and radial stability to a rotor of a passive magnetic bearing system when the rotor is not rotating and when it is rotating. In the passive magnetic bearing system, the rotor has a vertical axis of rotation. Without the journal bearing, the rotor is vertically and radially unstable when stationary, and is vertically stable and radially unstable when rotating.

  3. Therapeutic Efficacy of a {sup 188}Re-Labeled {alpha}-Melanocyte-Stimulating Hormone Peptide Analog in Murine and Human Melanoma-Bearing Mouse Models

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yubin; Owen, Nellie K.; Fisher, Darrell R.; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-01-01

    The purpose of this study was to examine the therapeutic efficacy of {sup 188}Re-(Arg{sup 11})CCMSH in the B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. Method: (Arg11)CCMSH was synthesized and labeled with {sup 188}Re to form {sup 188}Re-(Agr{sup 11})CCMSH. B16/F1 melanoma tumor bearing mice were administrated with 200 Ci, 600 Ci and 2x400 Ci of {sup 188}Re-(Arg{sup 11})CCMSH via the tail vein, respectively. TXM13 melanoma tumor hearing mice were separately injected with 600 Ci, 2x400 Ci and 1000 Ci of 100Re-(Arg{sup 11})CCMSH through the tail vein. Two groups of 10 mice bearing either B16/F1 or TXM13 tumors were injected with saline as untreated controls. Results: In contrast to the untreated control group, {sup 188}Re(Arg11)CCMSH yielded rapid and lasting therapeutic effects in the treatment groups with either B16/F1 or TXM13 tumors. The tumor growth rate was reduced and the survival rate was prolonged in the treatment groups. Treatment with 2x400 Ci of {sup 188}Re-Arg{sup 11}CCMSH significantly extended the mean life of B16/F1 tumor mice (p<0.05), while the mean life of TXm13 tumor mice was significantly prolonged after treatment with 600 Ci and 1000 Ci doses of {sup 188}Re-(Arg{sup 11})CCMSH (p<0.05 High-dose {sup 188}Re-(Arg{sup 11}))CCMSH produced no observed normal-tissue toxicity. Conclusions: The therapy study results revealed that {sup 188}Re-Arg11 CCMSH yielded significant therapeutic effects in both B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. {sup 188}Re-(Arg{sup 11})CCMSH appears to be a promising radiolabeled peptide for targeted radionuclide therapy of melanoma.

  4. Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears.

    Science.gov (United States)

    Liu, Shiping; Lorenzen, Eline D; Fumagalli, Matteo; Li, Bo; Harris, Kelley; Xiong, Zijun; Zhou, Long; Korneliussen, Thorfinn Sand; Somel, Mehmet; Babbitt, Courtney; Wray, Greg; Li, Jianwen; He, Weiming; Wang, Zhuo; Fu, Wenjing; Xiang, Xueyan; Morgan, Claire C; Doherty, Aoife; O'Connell, Mary J; McInerney, James O; Born, Erik W; Dalén, Love; Dietz, Rune; Orlando, Ludovic; Sonne, Christian; Zhang, Guojie; Nielsen, Rasmus; Willerslev, Eske; Wang, Jun

    2014-05-08

    Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Mechanism of the Quorum-Quenching Lactonase (AiiA) from Bacillus thuringiensis. 2. Substrate Modeling and Active Site Mutations

    Energy Technology Data Exchange (ETDEWEB)

    Momb, Jessica; Wang, Canhui; Liu, Dali; Thomas, Pei W.; Petsko, Gregory A.; Guo, Hua; Ringe, Dagmar; Fast, Walter (UNM); (Brandeis); (Texas)

    2008-12-02

    The N-acyl-l-homoserine lactone hydrolases (AHL lactonases) have attracted considerable attention because of their ability to quench AHL-mediated quorum-sensing pathways in Gram-negative bacteria and because of their relation to other enzymes in the metallo-{beta}-lactamase superfamily. To elucidate the detailed catalytic mechanism of AHL lactonase, mutations are made on residues that presumably contribute to substrate binding and catalysis. Steady-state kinetic studies are carried out on both the wild-type and mutant enzymes using a spectrum of substrates. Two mutations, Y194F and D108N, present significant effects on the overall catalysis. On the basis of a high-resolution structural model of the enzyme-product complex, a hybrid quantum mechanical/molecular mechanical method is used to model the substrate binding orientation and to probe the effect of the Y194F mutation. Combining all experimental and computational results, we propose a detailed mechanism for the ring-opening hydrolysis of AHL substrates as catalyzed by the AHL lactonase from Bacillus thuringiensis. Several features of the mechanism that are also found in related enzymes are discussed and may help to define an evolutionary thread that connects the hydrolytic enzymes of this mechanistically diverse superfamily.

  6. Improved gas thrust bearings

    Science.gov (United States)

    Anderson, W. J.; Etsion, I.

    1979-01-01

    Two variations of gas-lubricated thrust bearings extend substantially load-carrying range over existing gas bearings. Dual-Action Gas Thrust Bearing's load-carrying capacity is more than ninety percent greater than that of single-action bearing over range of compressibility numbers. Advantages of Cantilever-mounted Thrust Bearing are greater tolerance to dirt ingestion, good initial lift-off characteristics, and operational capability over wide temperature range.

  7. Amino- and Carboxyl-Terminal CCR5 Mutations in Brazilian HIV-1-Infected Women and Homology Model of p.L55Q CCR5 Mutant.

    Science.gov (United States)

    Costa, Giselle Calasans de Souza; Nunes, Marcio Roberto T; Jesus, Jaqueline Goes; Novaes, Thiago; Cardoso, Jedson Ferreira; Sousa Júnior, Edivaldo Costa; Santos, Edson de Souza; Galvão-Castro, Bernardo; Zanette, Dalila Luciola; Gonçalves, Marilda de Souza; Alcantara, Luiz Carlos Junior

    2015-07-01

    Genetic factors from an HIV-1 host can affect the rate of progression to AIDS and HIV infection. To investigate the frequency of mutations in the CCR5 gene, HIV-1 samples from infected women and uninfected individuals were selected for sequencing of the CCR5 gene regions encoding the N- and C-terminal protein domains. Physicochemical CCR5 modeling and potential protein domain analysis were performed in order to evaluate the impact of the mutations found in the properties and structure of CCR5. The p.L55Q mutation in the N-terminal protein domain was observed only in uninfected individuals, with an allelic frequency of 1.8%. Physicochemical analysis revealed that the p.L55Q mutation magnified the flexibility and accessibility profiles and the modeling of CCR5 structures showed resulting in a small deviation to the right, as well as a hydrophobic to hydrophilic property alteration. The p.L55Q mutation also resulted in a slight modification of the electrostatic load of this region. Additionally, three novel silent mutations were found at the C-terminal coding region among HIV-1-infected women. The results suggest that the p.L55Q mutation might alter CCR5 conformation. Further studies should be conducted to verify the role of this mutation in HIV-1 susceptibility.

  8. Mutational Mapping and Modeling of the Binding Site for (S)-Citalopram in the Human Serotonin Transporter

    DEFF Research Database (Denmark)

    Andersen, Jacob; Olsen, Lars; Hansen, Kasper B.

    2010-01-01

    The serotonin transporter (SERT) regulates extracellular levels of the neurotransmitter serotonin (5-hydroxytryptamine) in the brain by facilitating uptake of released 5-hydroxytryptamine into neuronal cells. SERT is the target for widely used antidepressant drugs, including imipramine, fluoxetine......, and (S)-citalopram, which are competitive inhibitors of the transport function. Knowledge of the molecular details of the antidepressant binding sites in SERT has been limited due to lack of structural data on SERT. Here, we present a characterization of the (S)-citalopram binding pocket in human SERT (h...... is functionally relevant from studying the effects of 64 point mutations around the putative substrate binding site. The mutational mapping also identify novel hSERT residues that are crucial for (S)-citalopram binding. The model defines the molecular determinants for (S)-citalopram binding to h...

  9. Bayesian Modeling for Genetic Anticipation in Presence of Mutational Heterogeneity: A Case Study in Lynch Syndrome

    DEFF Research Database (Denmark)

    Boonstra, Philip S; Mukherjee, Bhramar; Taylor, Jeremy M G

    2011-01-01

    birth cohorts. Using historic cancer registry data, we borrow from relative survival analysis methods to adjust for changes in age-specific incidence across birth cohorts. Our motivating case study comes from a Danish cancer register of 124 families with mutations in mismatch repair (MMR) genes known...

  10. Bayesian Modeling for Genetic Anticipation in Presence of Mutational Heterogeneity: A Case Study in Lynch Syndrome

    DEFF Research Database (Denmark)

    Boonstra, Philip S; Mukherjee, Bhramar; Taylor, Jeremy M G

    2011-01-01

    Summary Genetic anticipation, described by earlier age of onset (AOO) and more aggressive symptoms in successive generations, is a phenomenon noted in certain hereditary diseases. Its extent may vary between families and/or between mutation subtypes known to be associated with the disease phenoty...

  11. Proactive Routing Mutation Against Stealthy Distributed Denial of Service Attacks – Metrics, Modeling and Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Qi; Al-Shaer, Ehab; Chatterjee, Samrat; Halappanavar, Mahantesh; Oehmen, Christopher S.

    2018-04-01

    The Infrastructure Distributed Denial of Service (IDDoS) attacks continue to be one of the most devastating challenges facing cyber systems. The new generation of IDDoS attacks exploit the inherent weakness of cyber infrastructure including deterministic nature of routes, skew distribution of flows, and Internet ossification to discover the network critical links and launch highly stealthy flooding attacks that are not observable at the victim end. In this paper, first, we propose a new metric to quantitatively measure the potential susceptibility of any arbitrary target server or domain to stealthy IDDoS attacks, and es- timate the impact of such susceptibility on enterprises. Second, we develop a proactive route mutation technique to minimize the susceptibility to these attacks by dynamically changing the flow paths periodically to invalidate the adversary knowledge about the network and avoid targeted critical links. Our proposed approach actively changes these network paths while satisfying security and qualify of service requirements. We present an integrated approach of proactive route mutation that combines both infrastructure-based mutation that is based on reconfiguration of switches and routers, and middle-box approach that uses an overlay of end-point proxies to construct a virtual network path free of critical links to reach a destination. We implemented the proactive path mutation technique on a Software Defined Network using the OpendDaylight controller to demonstrate a feasible deployment of this approach. Our evaluation validates the correctness, effectiveness, and scalability of the proposed approaches.

  12. Molecular Modeling of Estrogen Receptor alpha Mutated Breast Cancer to Guide New Therapeutic Strategies

    Science.gov (United States)

    2017-10-01

    to the wildtype lines regardless of E2 induction (Figure 4). These findings indicate that the D538G mutation is creating a unique transcriptional...lab). She initially started this project before it was funded by the DOD. She has been in charge of the molecular biology work needed to introduce

  13. Hybrid method to solve HP model on 3D lattice and to probe protein stability upon amino acid mutations.

    Science.gov (United States)

    Guo, Yuzhen; Tao, Fengying; Wu, Zikai; Wang, Yong

    2017-09-21

    Predicting protein structure from amino acid sequence is a prominent problem in computational biology. The long range interactions (or non-local interactions) are known as the main source of complexity for protein folding and dynamics and play the dominant role in the compact architecture. Some simple but exact model, such as HP model, captures the pain point for this difficult problem and has important implications to understand the mapping between protein sequence and structure. In this paper, we formulate the biological problem into optimization model to study the hydrophobic-hydrophilic model on 3D square lattice. This is a combinatorial optimization problem and known as NP-hard. Particle swarm optimization is utilized as the heuristic framework to solve the hard problem. To avoid premature in computation, we incorporated the Tabu search strategy. In addition, a pulling strategy was designed to accelerate the convergence of algorithm based on the characteristic of native protein structure. Together a novel hybrid method combining particle swarm optimization, Tabu strategy, and pulling strategy can fold the amino acid sequences on 3D square lattice efficiently. Promising results are reported in several examples by comparing with existing methods. This allows us to use this tool to study the protein stability upon amino acid mutation on 3D lattice. In particular, we evaluate the effect of single amino acid mutation and double amino acids mutation via 3D HP lattice model and some useful insights are derived. We propose a novel hybrid method to combine several heuristic strategies to study HP model on 3D lattice. The results indicate that our hybrid method can predict protein structure more accurately and efficiently. Furthermore, it serves as a useful tools to probe the protein stability on 3D lattice and provides some biological insights.

  14. Radial magnetic bearings: An overview

    Directory of Open Access Journals (Sweden)

    Weiyu Zhang

    Full Text Available Radial magnetic bearings (RMBs are one of the most commonly used magnetic bearings. They are used widely in the field of ultra-high speed and ultra-precise numerical control machine tools, bearingless motors, high speed flywheels, artificial heart pumps, and molecular pumps, and they are being strengthened and extended in various important areas. In this paper, a comprehensive overview is given of different bearing topologies of RMBs with different stator poles that differ in their construction, the driving mode of electromagnets, power consumption, cost, magnetic circuits, and symmetry. RMBs with different poles and couplings between the two bearing axes in the radial direction responsible for cross-coupling generation are compared. In addition, different shaped rotors are compared, as the performances of magnetic bearing-rotor systems are of great concern to rotor constructions. Furthermore, the parameter design methods, the mathematical models and control strategies of the RMBs are described in detail. From the comparison of topologies, models and control methods for RMBs, the advantages, disadvantages and utilizable perspectives are also analyzed. Moreover, several possible development trends of the RMBs are discussed. Keywords: Radial magnetic bearings (RMBs, Topologies, Mathematical mode, Control strategies, Development trends

  15. A Markov chain description of the stepwise mutation model: local and global behaviour of the allele process.

    Science.gov (United States)

    Caliebe, Amke; Jochens, Arne; Krawczak, Michael; Rösler, Uwe

    2010-09-21

    The stepwise mutation model (SMM) is a simple, widely used model to describe the evolutionary behaviour of microsatellites. We apply a Markov chain description of the SMM and derive the marginal and joint properties of this process. In addition to the standard SMM, we also consider the normalised allele process. In contrast to the standard process, the normalised process converges to a stationary distribution. We show that the marginal stationary distribution is unimodal. The standard and normalised processes capture the global and the local behaviour of the SMM, respectively. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  16. Mice overexpressing both non-mutated human SOD1 and mutated SOD1G93A genes: a competent experimental model for studying iron metabolism in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Anna eGajowiak

    2016-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disease characterized by degeneration and loss of motor neurons in the spinal cord, brainstem and motor cortex. Up to 10% of ALS cases are inherited (familial, fALS and associated with mutations, frequently in the superoxide dismutase 1 (SOD1 gene. Rodent transgenic models of ALS are often used to elucidate a complex pathogenesis of this disease. Of importance, both ALS patients and animals carrying mutated human SOD1 gene show symptoms of oxidative stress and iron metabolism misregulation. The aim of our study was to characterize changes in iron metabolism in one of the most commonly used models of ALS – transgenic mice overexpressing human mutated SOD1G93A gene. We analyzed the expression of iron-related genes in asymptomatic, 2-month old and symptomatic, 4-month old SOD1G93A mice. In parallel, respective age-matched mice overexpressing human non-mutated SOD1 transgene and control mice were analyzed. We demonstrate that the overexpression of both SOD1 and SOD1G93A genes account for a substantial increase in SOD1 protein levels and activity in selected tissues and that not all the changes in iron metabolism genes expression are specific for the overexpression of the mutated form of SOD1.

  17. Scaling laws for radial foil bearings

    Science.gov (United States)

    Honavara Prasad, Srikanth

    The effects of fluid pressurization, structural deformation of the compliant members and heat generation in foil bearings make the design and analysis of foil bearings very complicated. The complex fluid-structural-thermal interactions in foil bearings also make modeling efforts challenging because these phenomena are governed by highly non-linear partial differential equations. Consequently, comparison of various bearing designs require detailed calculation of the flow fields (velocities, pressures), bump deflections (structural compliance) and heat transfer phenomena (viscous dissipation in the fluid, frictional heating, temperature profile etc.,) resulting in extensive computational effort (time/hardware). To obviate rigorous computations and aid in feasibility assessments of foil bearings of various sizes, NASA developed the "rule of thumb" design guidelines for estimation of journal bearing load capacity. The guidelines are based on extensive experimental data. The goal of the current work is the development of scaling laws for radial foil bearings to establish an analytical "rule of thumb" for bearing clearance and bump stiffness. The use of scale invariant Reynolds equation and experimentally observed NASA "rule of thumb" yield scale factors which can be deduced from first principles. Power-law relationships between: a. Bearing clearance and bearing radius, and b. bump stiffness and bearing radius, are obtained. The clearance and bump stiffness values obtained from scaling laws are used as inputs for Orbit simulation to study various cases. As the clearance of the bearing reaches the dimensions of the material surface roughness, asperity contact breaks the fluid film which results in wear. Similarly, as the rotor diameter increases (requiring larger bearing diameters), the load capacity of the fluid film should increase to prevent dry rubbing. This imposes limits on the size of the rotor diameter and consequently bearing diameter. Therefore, this thesis aims

  18. Mathematical model for the growth of P. aeruginosa and four mutator strains in sub-MIC concentration of Ciprofloxacin

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo; Madsen, Henrik

    is that the presence of antibiotic results in selection of mutators in the lungs of CF patients, as these bacteria has a higher fitness under the presence of antibiotics. The goal of this study is to model the growth of P. aeruginosa and four different mutator strains (PAO1 mutT, mutY, mutM and mutM-mutY mutants) when...... growing under sub-MIC Ciprofloxacin concentration (0.1 μg/ml), in order to describe the growth pattern under the presence of antibiotic. Data available for the modelling process is bioscreen measurements of the bacterial content as a function of time for each bacteria strain growing in LB media...... with and without the presence of Ciprofloxacin. The growth of the bacteria strains is modelled with a continuous-discrete time stochastic state space model consisting of a continuous time state equation expressed as a system of stochastic differential equations and a discrete time measurement equation. The model...

  19. A Human Neural Crest Stem Cell-Derived Dopaminergic Neuronal Model Recapitulates Biochemical Abnormalities in GBA1 Mutation Carriers

    Directory of Open Access Journals (Sweden)

    Shi-Yu Yang

    2017-03-01

    Full Text Available Numerically the most important risk factor for the development of Parkinson's disease (PD is the presence of mutations in the glucocerebrosidase GBA1 gene. In vitro and in vivo studies show that GBA1 mutations reduce glucocerebrosidase (GCase activity and are associated with increased α-synuclein levels, reflecting similar changes seen in idiopathic PD brain. We have developed a neural crest stem cell-derived dopaminergic neuronal model that recapitulates biochemical abnormalities in GBA1 mutation-associated PD. Cells showed reduced GCase protein and activity, impaired macroautophagy, and increased α-synuclein levels. Advantages of this approach include easy access to stem cells, no requirement to reprogram, and retention of the intact host genome. Treatment with a GCase chaperone increased GCase protein levels and activity, rescued the autophagic defects, and decreased α-synuclein levels. These results provide the basis for further investigation of GCase chaperones or similar drugs to slow the progression of PD.

  20. Mutation identification in a canine model of X-linked ectodermal dysplasia

    OpenAIRE

    Casal, Margret L.; Scheidt, Jennifer L.; Rhodes, James L.; Henthorn, Paula S.; Werner, Petra

    2005-01-01

    X-linked hypohidrotic ectodermal dysplasia (XHED), an inherited disease recognized in humans, mice, and cattle, is characterized by hypotrichosis, a reduced number or absence of sweat glands, and missing or malformed teeth. In a subset of affected individuals and animals, mutations in the EDA gene (formerly EDI), coding for ectodysplasin, have been found to cause this phenotype. Ectodysplasin is a homotrimeric transmembrane protein with an extracellular TNF-like domain, which has been shown t...

  1. Implications of fALS Mutations on Sod1 Function and Oligomerization in Cell Models.

    Science.gov (United States)

    Brasil, Aline A; Magalhães, Rayne S S; De Carvalho, Mariana D C; Paiva, Isabel; Gerhardt, Ellen; Pereira, Marcos D; Outeiro, Tiago F; Eleutherio, Elis C A

    2017-09-07

    Among the familial forms of amyotrophic lateral sclerosis (fALS), 20% are associated with the Cu,Zn-superoxide dismutase (Sod1). fALS is characterized by the accumulation of aggregated proteins and the increase in oxidative stress markers. Here, we used the non-invasive bimolecular fluorescence complementation (BiFC) assay in human H4 cells to investigate the kinetics of aggregation and subcellular localization of Sod1 mutants. We also studied the effect of the different Sod1 mutants to respond against oxidative stress by following the levels of reactive oxygen species (ROS) after treatment with hydrogen peroxide. Our results showed that only 30% of cells transfected with A4VSod1 showed no inclusions while for the other Sod1 mutants tested (L38V, G93A and G93C), this percentage was at least 70%. In addition, we found that 10% of cells transfected with A4VSod1 displayed more than five inclusions per cell and that A4V and G93A Sod1 formed inclusions more rapidly than L38V and G93C Sod1. Expression of WTSod1 significantly decreased the intracellular oxidation levels in comparison with expression of fALS Sod1 mutants, suggesting the mutations induce a functional impairment. All fALS mutations impaired nuclear localization of Sod1, which is important for maintaining genomic stability. Consistently, expression of WTSod1, but not of fALS Sod1 mutants, reduced DNA damage, as measured by the comet assay. Altogether, our study sheds light into the effects of fALS Sod1 mutations on inclusion formation, dynamics, and localization as well as on antioxidant response, opening novel avenues for investigating the role of fALS Sod1 mutations in pathogenesis.

  2. Molecular Modeling of Estrogen Receptor Alpha Mutated Breast Cancer to Guide New Therapeutic Strategies

    Science.gov (United States)

    2017-10-01

    ABSTRACT The expression of estrogen receptor alpha (ER) is assayed in every breast cancer biopsy at the time of diagnosis with the majority of tumors (~70... expressing ER. Hormone therapy is given to patients with ER expressing tumors for years after surgical resection to block the creation of estrogens...resistant breast tumors that harbor ER LBD mutations. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES

  3. A Molecular Modeling Study of the Hydroxyflutamide Resistance Mechanism Induced by Androgen Receptor Mutations

    Directory of Open Access Journals (Sweden)

    Hong-Li Liu

    2017-08-01

    Full Text Available Hydroxyflutamide (HF, an active metabolite of the first generation antiandrogen flutamide, was used in clinic to treat prostate cancer targeting androgen receptor (AR. However, a drug resistance problem appears after about one year’s treatment. AR T877A is the first mutation that was found to cause a resistance problem. Then W741C_T877A and F876L_T877A mutations were also reported to cause resistance to HF, while W741C and F876L single mutations cannot. In this study, molecular dynamics (MD simulations combined with the molecular mechanics generalized Born surface area (MM-GBSA method have been carried out to analyze the interaction mechanism between HF and wild-type (WT/mutant ARs. The obtained results indicate that AR helix 12 (H12 plays a pivotal role in the resistance of HF. It can affect the coactivator binding site at the activation function 2 domain (AF2, surrounded by H3, H4, and H12. When H12 closes to the AR ligand-binding domain (LBD like a lid, the coactivator binding site can be formed to promote transcription. However, once H12 is opened to expose LBD, the coactivator binding site will be distorted, leading to invalid transcription. Moreover, per-residue free energy decomposition analyses indicate that N705, T877, and M895 are vital residues in the agonist/antagonist mechanism of HF.

  4. TEMPERATURE DIAGNOSTICS OF GAS TURBINE ENGINE BEARINGS

    Directory of Open Access Journals (Sweden)

    R. V. Birukov

    2014-01-01

    Full Text Available The objective of the current research was to develop methodology for diagnosing industrial gas turbine engine bearings using the standard performance parameters. This paper presents mathematical thermal model of combined thrust and radial bearing and provides the model application examples for diagnostics.

  5. Single-nucleotide mutation matrix: a new model for predicting the NF-κB DNA binding sites.

    Science.gov (United States)

    Du, Wenxin; Gao, Jing; Wang, Tingting; Wang, Jinke

    2014-01-01

    In this study, we established a single nucleotide mutation matrix (SNMM) model based on the relative binding affinities of NF-κB p50 homodimer to a wild-type binding site (GGGACTTTCC) and its all single-nucleotide mutants detected with the double-stranded DNA microarray. We evaluated this model by scoring different groups of 10-bp DNA sequences with this model and analyzing the correlations between the scores and the relative binding affinities detected with three wet experiments, including the electrophoresis mobility shift assay (EMSA), the protein-binding microarray (PBM) and the systematic evolution of ligands by exponential enrichment-sequencing (SELEX-Seq). The results revealed that the SNMM scores were strongly correlated with the detected binding affinities. We also scored the DNA sequences with other three models, including the principal coordinate (PC) model, the position weight matrix scoring algorithm (PWMSA) model and the Match model, and analyzed the correlations between the scores and the detected binding affinities. In comparison with these models, the SNMM model achieved reliable results. We finally determined 0.747 as the optimal threshold for predicting the NF-κB DNA-binding sites with the SNMM model. The SNMM model thus provides a new alternative model for scoring the relative binding affinities of NF-κB to the 10-bp DNA sequences and predicting the NF-κB DNA-binding sites.

  6. Mutational spectrum drives the rise of mutator bacteria.

    Science.gov (United States)

    Couce, Alejandro; Guelfo, Javier R; Blázquez, Jesús

    2013-01-01

    Understanding how mutator strains emerge in bacterial populations is relevant both to evolutionary theory and to reduce the threat they pose in clinical settings. The rise of mutator alleles is understood as a result of their hitchhiking with linked beneficial mutations, although the factors that govern this process remain unclear. A prominent but underappreciated fact is that each mutator allele increases only a specific spectrum of mutational changes. This spectrum has been speculated to alter the distribution of fitness effects of beneficial mutations, potentially affecting hitchhiking. To study this possibility, we analyzed the fitness distribution of beneficial mutations generated from different mutator and wild-type Escherichia coli strains. Using antibiotic resistance as a model system, we show that mutational spectra can alter these distributions substantially, ultimately determining the competitive ability of each strain across environments. Computer simulation showed that the effect of mutational spectrum on hitchhiking dynamics follows a non-linear function, implying that even slight spectrum-dependent fitness differences are sufficient to alter mutator success frequency by several orders of magnitude. These results indicate an unanticipated central role for the mutational spectrum in the evolution of bacterial mutation rates. At a practical level, this study indicates that knowledge of the molecular details of resistance determinants is crucial for minimizing mutator evolution during antibiotic therapy.

  7. Mutational spectrum drives the rise of mutator bacteria.

    Directory of Open Access Journals (Sweden)

    Alejandro Couce

    Full Text Available Understanding how mutator strains emerge in bacterial populations is relevant both to evolutionary theory and to reduce the threat they pose in clinical settings. The rise of mutator alleles is understood as a result of their hitchhiking with linked beneficial mutations, although the factors that govern this process remain unclear. A prominent but underappreciated fact is that each mutator allele increases only a specific spectrum of mutational changes. This spectrum has been speculated to alter the distribution of fitness effects of beneficial mutations, potentially affecting hitchhiking. To study this possibility, we analyzed the fitness distribution of beneficial mutations generated from different mutator and wild-type Escherichia coli strains. Using antibiotic resistance as a model system, we show that mutational spectra can alter these distributions substantially, ultimately determining the competitive ability of each strain across environments. Computer simulation showed that the effect of mutational spectrum on hitchhiking dynamics follows a non-linear function, implying that even slight spectrum-dependent fitness differences are sufficient to alter mutator success frequency by several orders of magnitude. These results indicate an unanticipated central role for the mutational spectrum in the evolution of bacterial mutation rates. At a practical level, this study indicates that knowledge of the molecular details of resistance determinants is crucial for minimizing mutator evolution during antibiotic therapy.

  8. From disease modelling to personalised therapy in patients with CEP290 mutations [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Elisa Molinari

    2017-05-01

    Full Text Available Mutations that give rise to premature termination codons are a common cause of inherited genetic diseases. When transcripts containing these changes are generated, they are usually rapidly removed by the cell through the process of nonsense-mediated decay. Here we discuss observed changes in transcripts of the centrosomal protein CEP290 resulting not from degradation, but from changes in exon usage. We also comment on a landmark paper (Drivas et al. Sci Transl Med. 2015 where modelling this process of exon usage may be used to predict disease severity in CEP290 ciliopathies, and how understanding this process may potentially be used for therapeutic benefit in the future.

  9. Patient iPSC-derived neurons for disease modeling of frontotemporal dementia with mutation in CHMP2B

    DEFF Research Database (Denmark)

    Zhang, Yu; Schmid, Benjamin; Nikolaisen, Nanett Kvist

    2017-01-01

    The truncated mutant form of the charged multivesicular body protein 2B (CHMP2B) is causative for frontotemporal dementia linked to chromosome 3 (FTD3). CHMP2B is a constituent of the endosomal sorting complex required for transport (ESCRT) and, when mutated, disrupts endosome-to-lysosome traffic...... in neurodegenerative diseases. All phenotypes observed in FTD3 neurons were rescued in CRISPR/Cas9-edited isogenic controls. These findings illustrate the relevance of our patient-specific in vitro models and open up possibilities for drug target development....

  10. [Compound K suppresses myeloid-derived suppressor cells in a mouse model bearing CT26 colorectal cancer xenograft].

    Science.gov (United States)

    Wang, Rong; Li, Yalin; Wang, Wuzhou; Zhou, Meijuan; Cao, Zhaohui

    2015-05-01

    To investigate the effect of ginseng-derived compound K (C-K) on apoptosis, immunosuppressive activity, and pro-inflammatory cytokine production of myeloid-derived suppressor cells (MDSCs) from mice bearing colorectal cancer xenograft. Flow-sorted bone marrow MDSCs from Balb/c mice bearing CT26 tumor xenograft were treated with either C-K or PBS for 96 h and examined for apoptosis with Annexin V/7-AAD, Cox-2 and Arg-1 expressions using qRT-PCR, and supernatant IL-1β, IL-6, and IL-17 levels with ELISA. C-K- or PBS-treated MDSCs were subcutaneously implanted along with CT26 tumor cells in WT Balb/c mice, and the tumor size and morphology were evaluated 21 days later. C-K treatment significantly increased the percentages of early and late apoptotic MDSCs in vitro (Pimmunosuppresive effect of MDSCs to inhibit tumor cell proliferation in mice, which suggests a new strategy of tumor therapy by targeting MDSCs.

  11. Experiments with needle bearings

    Science.gov (United States)

    Ferretti, Pericle

    1933-01-01

    Experiments and results are presented in testing needle bearings, especially in comparison with roller bearings. Reduction in coefficient of friction is discussed as well as experimental methods and recording devices.

  12. Rolling Bearing Life Prediction, Theory, and Application

    Science.gov (United States)

    Zaretsky, Erwin V.

    2016-01-01

    A tutorial is presented outlining the evolution, theory, and application of rolling-element bearing life prediction from that of A. Palmgren, 1924; W. Weibull, 1939; G. Lundberg and A. Palmgren, 1947 and 1952; E. Ioannides and T. Harris, 1985; and E. Zaretsky, 1987. Comparisons are made between these life models. The Ioannides-Harris model without a fatigue limit is identical to the Lundberg-Palmgren model. The Weibull model is similar to that of Zaretsky if the exponents are chosen to be identical. Both the load-life and Hertz stress-life relations of Weibull, Lundberg and Palmgren, and Ioannides and Harris reflect a strong dependence on the Weibull slope. The Zaretsky model decouples the dependence of the critical shear stress-life relation from the Weibull slope. This results in a nominal variation of the Hertz stress-life exponent. For 9th- and 8th-power Hertz stress-life exponents for ball and roller bearings, respectively, the Lundberg-Palmgren model best predicts life. However, for 12th- and 10th-power relations reflected by modern bearing steels, the Zaretsky model based on the Weibull equation is superior. Under the range of stresses examined, the use of a fatigue limit would suggest that (for most operating conditions under which a rolling-element bearing will operate) the bearing will not fail from classical rolling-element fatigue. Realistically, this is not the case. The use of a fatigue limit will significantly overpredict life over a range of normal operating Hertz stresses. (The use of ISO 281:2007 with a fatigue limit in these calculations would result in a bearing life approaching infinity.) Since the predicted lives of rolling-element bearings are high, the problem can become one of undersizing a bearing for a particular application. Rules had been developed to distinguish and compare predicted lives with those actually obtained. Based upon field and test results of 51 ball and roller bearing sets, 98 percent of these bearing sets had acceptable

  13. Molecular Consequences of the SERPINH1/HSP47 Mutation in the Dachshund Natural Model of Osteogenesis Imperfecta.

    Science.gov (United States)

    Lindert, Uschi; Weis, Mary Ann; Rai, Jyoti; Seeliger, Frank; Hausser, Ingrid; Leeb, Tosso; Eyre, David; Rohrbach, Marianne; Giunta, Cecilia

    2015-07-17

    Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of OI in dachshunds (L326P) as well as in humans (one single case with a L78P mutation). To elucidate the disease mechanism underlying OI in the dog model, we applied a range of biochemical assays to mutant and control skin fibroblasts as well as on bone samples. These experiments revealed that type I collagen synthesized by mutant cells had decreased electrophoretic mobility. Procollagen was retained intracellularly with concomitant dilation of ER cisternae and activation of the ER stress response markers GRP78 and phospho-eIF2α, thus suggesting a defect in procollagen processing. In line with the migration shift detected on SDS-PAGE of cell culture collagen, extracts of bone collagen from the OI dog showed a similar mobility shift, and on tandem mass spectrometry, the chains were post-translationally overmodified. The bone collagen had a higher content of pyridinoline than control dog bone. We conclude that the SERPINH1 mutation in this naturally occurring model of OI impairs how HSP47 acts as a chaperone in the ER. This results in abnormal post-translational modification and cross-linking of the bone collagen. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Song Min

    2011-08-01

    Full Text Available Abstract Background Amyloid plaques, a pathological hallmark of Alzheimer's disease (AD, are accompanied by activated microglia. The role of activated microglia in the pathogenesis of AD remains controversial: either clearing Aβ deposits by phagocytosis or releasing proinflammatory cytokines and cytotoxic substances. Microglia can be activated via toll-like receptors (TLRs, a class of pattern-recognition receptors in the innate immune system. We previously demonstrated that an AD mouse model homozygous for a loss-of-function mutation of TLR4 had increases in Aβ deposits and buffer-soluble Aβ in the brain as compared with a TLR4 wild-type AD mouse model at 14-16 months of age. However, it is unknown if TLR4 signaling is involved in initiation of Aβ deposition as well as activation and recruitment of microglia at the early stage of AD. Here, we investigated the role of TLR4 signaling and microglial activation in early stages using 5-month-old AD mouse models when Aβ deposits start. Methods Microglial activation and amyloid deposition in the brain were determined by immunohistochemistry in the AD models. Levels of cerebral soluble Aβ were determined by ELISA. mRNA levels of cytokines and chemokines in the brain and Aβ-stimulated monocytes were quantified by real-time PCR. Cognitive functions were assessed by the Morris water maze. Results While no difference was found in cerebral Aβ load between AD mouse models at 5 months with and without TLR4 mutation, microglial activation in a TLR4 mutant AD model (TLR4M Tg was less than that in a TLR4 wild-type AD model (TLR4W Tg. At 9 months, TLR4M Tg mice had increased Aβ deposition and soluble Aβ42 in the brain, which were associated with decrements in cognitive functions and expression levels of IL-1β, CCL3, and CCL4 in the hippocampus compared to TLR4W Tg mice. TLR4 mutation diminished Aβ-induced IL-1β, CCL3, and CCL4 expression in monocytes. Conclusion This is the first demonstration of TLR4

  15. Theoretical Modeling for the X-ray Spectroscopy of Iron-bearing MgSiO3 under High Pressure

    Science.gov (United States)

    Wang, X.; Tsuchiya, T.

    2012-12-01

    The behaviors of iron (Fe) in MgSiO3 perovskite, including valence state, spin state, and chemical environments, at high pressures are of fundamental importance for more detailed understanding the properties of the Earth's lower mantle. The pressure induced spin transition of Fe-bearing MgO and MgSiO3 are detected often by using high-resolution K-edge X-ray emission spectroscopy (XES) [1,2,3] and confirmed by theoretical simulations. [4,5] Since the Fe K-edge XES is associated to the 3p orbital, which is far from the valence orbitals (3d and 4s), it provides no information about its coordination environments. However, the Fe L-edge XES and X-ray absorption spectroscopy (XAS) can directly present the distribution and intensity of Fe-3d character. To identify both the spin states and the coordination environments of iron-bearing MgSiO3, we systematically investigate the L-edge XAS, XES and X-ray photoelectron (XPS) spectroscopy of Fe2+- and Fe3+-bearing MgSiO3 under high pressure by using the first-principles density functional method combined with the slater-transition method. Our results show that Fe2+ and Fe3+ can be distinguished easily by taking the XPS spectra. The spin transition of Fe2+ and Fe3+ can also be clearly certified by XAS and XES. Interestingly, the broadness of L-edge XES of Fe changes depending on the iron position, meaning that its coordination environment might also be distinguishable by using high-resolution XES measurements. Research supported by the Ehime University G-COE program and KAKENHI. [1] James Badro, Guillaume Fiquet, FranÇois Guyot, Jean-Pascal Rueff, Viktor V. Struzhkin, György VankÓ, and Giulio Monaco. Science 300, 789 (2003), [2] James Badro, Jean-Pascal Rueff, György VankÓ, Giulio Monaco, Guillaume Fiquet, and FranÇois Guyot, Science 305, 383 (2004), [3] Jung-Fu Lin, Viktor V. Struzhkin, Steven D. Jacobsen, Michael Y. Hu, Paul Chow, Jennifer Kung, Haozhe Liu, Ho-kwang Mao, and Gussell J. Hemley, Nature 436, 377 (2005). [4

  16. Methodology for Detecting Malfunctions and Evaluating the Maintenance Effectiveness in Wind Turbine Generator Bearings Using Generic versus Specific Models from SCADA Data

    Directory of Open Access Journals (Sweden)

    Miguel A. Rodríguez-López

    2018-03-01

    Full Text Available This article offers reasons to defend the use of generic behavior models as opposed to specific models in applications to determine component degradation. The term generic models refers to models based on operating data from various units, whereas specific models are calculated using operating data taken from a single unit. Moreover, generic models, used in combination with a status indicator, show excellent capacity for detecting anomalies in the equipment and for evaluating the effectiveness of the maintenance actions, resulting in lower development and maintenance costs for the operating firm. Artificial neural networks and moving means were used to calculate the degradation indicators, based on the remainders in the model. The models were developed from operating data from fourteen wind turbines monitored over several years, and applied to the detection of faults in the bearings on the non-drive end of the generator. The use of generic models may not be recommendable for detecting faults in all cases, and the suitability will depend greatly on the context of the methodology developed to detect each type of fault, according to the element causing the fault and the fault mode, since each methodology requires a greater or lesser degree of precision in the model.

  17. A New Mouse Model of Limb-Girdle Muscular Dystrophy Type 2I Homozygous for the Common L276I Mutation Mimicking the Mild Phenotype in Humans

    DEFF Research Database (Denmark)

    Krag, Thomas O; Vissing, John

    2015-01-01

    Limb-girdle muscular dystrophy type 2I (LGMD2I) is caused by mutations in the Fukutin-related protein (FKRP) gene, leading to inadequate glycosylation of α-dystroglycan, an important protein linking the extracellular matrix to the cytoskeleton. We created a mouse model of the common FKRP L276I...... mutation and a hemizygous FKRP L276I knockout model. We studied histopathology and protein expression in the models at different ages and found that homozygous FKRP L276I mice developed a mild progressive myopathy with increased muscle regeneration and fibrosis starting from 1 year of age. This was likely...... in maintaining proper glycosylation of α-dystroglycan. The mild progression in the homozygous FKRP L276I model resembles that in patients with LGMD2I who are homozygous for the L276I mutation. This animal model could, therefore, be relevant for understanding the pathophysiology of and developing a treatment...

  18. A Mouse Model That Reproduces the Developmental Pathways and Site Specificity of the Cancers Associated With the Human BRCA1 Mutation Carrier State

    Directory of Open Access Journals (Sweden)

    Ying Liu

    2015-10-01

    Full Text Available Predisposition to breast and extrauterine Müllerian carcinomas in BRCA1 mutation carriers is due to a combination of cell-autonomous consequences of BRCA1 inactivation on cell cycle homeostasis superimposed on cell-nonautonomous hormonal factors magnified by the effects of BRCA1 mutations on hormonal changes associated with the menstrual cycle. We used the Müllerian inhibiting substance type 2 receptor (Mis2r promoter and a truncated form of the Follicle stimulating hormone receptor (Fshr promoter to introduce conditional knockouts of Brca1 and p53 not only in mouse mammary and Müllerian epithelia, but also in organs that control the estrous cycle. Sixty percent of the double mutant mice developed invasive Müllerian and mammary carcinomas. Mice carrying heterozygous mutations in Brca1 and p53 also developed invasive tumors, albeit at a lesser (30% rate, in which the wild type alleles were no longer present due to loss of heterozygosity. While mice carrying heterozygous mutations in both genes developed mammary tumors, none of the mice carrying only a heterozygous p53 mutation developed such tumors (P < 0.0001, attesting to a role for Brca1 mutations in tumor development. This mouse model is attractive to investigate cell-nonautonomous mechanisms associated with cancer predisposition in BRCA1 mutation carriers and to investigate the merit of chemo-preventive drugs targeting such mechanisms.

  19. MODELING AND ANALYSIS OF DYNAMICS IN BEARING SYSTEM OF DRILLING, MILLING AND BORING MACHINE WITH MONO-COLUMN

    Directory of Open Access Journals (Sweden)

    Yu. V. Vasilevich

    2015-01-01

    Full Text Available  FEM-analysis of dynamics in the bearing system of a heavy-duty machine tool has been carried out in the paper. This is a prospective variant for a large-size multi-purpose machine tool with a horizontal sliding ram. A saddle and a ram are moving vertically along a subtle mono-column. A rigid double-column is used in the existing analog machine tool. A static, modal and harmonic analysis of the bearing system with the mono-column has been made in the paper. It has been done with the help of FEM-simulation prior to fabrication of a prototype sample. Previously conducted calculations for the analog machine tool have shown good compatibility of FEM-calculation with experiments.Six common machine tool resonances have been revealed for the bearing system. Their oscillating cutting forces are actively exciting three-four resonance modes. Ranges of a flexure-torsion resonance (20–40 Hz and nose-diving resonances (70–90 Hz have been determined in the paper. The paper shows that the range of multi-wave resonances starts significantly higher from 140 Hz. These resonances are interconnected with bending oscillations of the ram and bucklings of the column walls which are matched with the oscillations. The paper demonstrates stability in resonance pattern. The torsional resonance of the column on the frequency of nearly 40 Hz is considered as the more dangerous one. Spindle rigidity goes down up to 3.8 Н/μm. It is possible to observe self-stabilization of the torsional resonance. Frequency of the torsional oscillations is practically unchangeable when there is a lifting or lowering down of the saddle and the ram. It is related to the migration of dynamical axis of torsion.Frequency-response characteristics of the bearing system have been constructed for various saddle positions on the column. Three frequency intervals that make it possible to carry out machining operation have been determined in the paper. The first interval is a static one. The

  20. Functional characterization of new mutations in Wilson disease gene (ATP7B) using the yeast model.

    Science.gov (United States)

    Papur, Ozlenen Simsek; Terzioglu, Orhan; Koc, Ahmet

    2015-01-01

    The Wilson disease gene, a copper transporting ATPase (Atp7b), is responsible for the sequestration of Cu into secretory vesicles, and this function is exhibited by the orthologous Ccc2p in the yeast. In this study, we aimed to characterize clinically relevant new mutations of human ATP7B (p.T788I, p.V1036I and p.R1038G-fsX83) in yeast lacking the CCC2 gene. Expression of human wild type ATP7B gene in ccc2Δ mutant yeast restored the growth deficiency and copper transport activity; however, expression of the mutant forms did not restore the copper transport functions and only partially supported the cell growth. Our data support that p.T788I, p.V1036I and p.R1038G-fsX83 mutations cause functional deficiency in ATP7B functions and suggest that these residues are important for normal ATP7B function. Copyright © 2015 Elsevier GmbH. All rights reserved.

  1. DNA Repair Domain Modeling Can Predict Cell Death and Mutation Frequency for Wide Range Spectrum of Radiation

    Science.gov (United States)

    Viger, Louise; Ponomarev, Artem L.; Plante, Ianik; Evain, Trevor; Penninckx, Sebastien; Blattnig, Steve R.; Costes, Sylvain V.

    2017-01-01

    Exploration missions to Mars and other destinations raise many questions about the health of astronauts. The continuous exposure of astronauts to galactic cosmic rays is one of the main concerns for long-term missions. Cosmic ionizing radiations are composed of different ions of various charges and energies notably, highly charged energy (HZE) particles. The HZE particles have been shown to be more carcinogenic than low-LET radiation, suggesting the severity of chromosomal aberrations induced by HZE particles is one possible explanation. However, most mathematical models predicting cell death and mutation frequency are based on directly fitting various HZE dose response and are in essence empirical approaches. In this work, we assume a simple biological mechanism to model DNA repair and use it to simultaneously explain the low- and high-LET response using the exact same fitting parameters. Our work shows that the geometrical position of DNA repair along tracks of heavy ions are sufficient to explain why high-LET particles can induce more death and mutations. Our model is based on assuming DNA double strand breaks (DSBs) are repaired within repair domain, and that any DSBs located within the same repair domain cluster into one repair unit, facilitating chromosomal rearrangements and increasing the probability of cell death. We introduced this model in 2014 using simplified microdosimetry profiles to predict cell death. In this work, we collaborated with NASA Johnson Space Center to generate more accurate microdosimetry profiles derived by Monte Carlo techniques, taking into account track structure of HZE particles and simulating DSBs in realistic cell geometry. We simulated 224 data points (D, A, Z, E) with the BDSTRACKS model, leading to a large coverage of LET from 10 to 2,400 keV/µm. This model was used to generate theoretical RBE for various particles and energies for both cell death and mutation frequencies. The RBE LET dependence is in agreement with

  2. Genomic evidence of widespread admixture from polar bears into brown bears during the last ice age.

    Science.gov (United States)

    Cahill, James A; Heintzman, Peter D; Harris, Kelley; Teasdale, Matthew D; Kapp, Joshua; Soares, André E Rodrigues; Stirling, Ian; Bradley, Daniel; Edwards, Ceiridwen J; Graim, Kiley; Kisleika, Aliaksandr A; Malev, Alexander V; Monaghan, Nigel; Green, Richard E; Shapiro, Beth

    2018-02-20

    Recent genomic analyses have provided substantial evidence for past periods of gene flow from polar bears (Ursus maritimus) into Alaskan brown bears (Ursus arctos), with some analyses suggesting a link between climate change and genomic introgression. However, because it has mainly been possible to sample bears from the present day, the timing, frequency, and evolutionary significance of this admixture remains unknown. Here, we analyze genomic DNA from three additional and geographically distinct brown bear populations, including two that lived temporally close to the peak of the last ice age. We find evidence of admixture in all three populations, suggesting that admixture between these species has been common in their recent evolutionary history. In addition, analyses of ten fossil bears from the now-extinct Irish population indicate that admixture peaked during the last ice age, when brown bear and polar bear ranges overlapped. Following this peak, the proportion of polar bear ancestry in Irish brown bears declined rapidly until their extinction. Our results support a model in which ice age climate change created geographically widespread conditions conducive to admixture between polar bears and brown bears, as is again occurring today. We postulate that this model will be informative for many admixing species pairs impacted by climate change. Our results highlight the power of paleogenomics to reveal patterns of evolutionary change that are otherwise masked in contemporary data.

  3. Novel temporary left ventricular assist system with hydrodynamically levitated bearing pump for bridge to decision: initial preclinical assessment in a goat model.

    Science.gov (United States)

    Kishimoto, Satoru; Takewa, Yoshiaki; Tsukiya, Tomonori; Mizuno, Toshihide; Date, Kazuma; Sumikura, Hirohito; Fujii, Yutaka; Ohnuma, Kentaro; Togo, Konomi; Katagiri, Nobumasa; Naito, Noritsugu; Kishimoto, Yuichiro; Nakamura, Yoshinobu; Nishimura, Motonobu; Tatsumi, Eisuke

    2018-03-01

    The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. We developed a new temporary left ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing. We used three adult goats (body weight, 58-68 kg) to investigate the 30-day performance and hemocompatibility of the newly developed left ventricular assist system, which included the pump, inflow and outflow cannulas, the extracorporeal circuit, and connectors. Hemodynamic, hematologic, and blood chemistry measurements were investigated as well as end-organ effect on necropsy. All goats survived for 30 days in good general condition. The blood pump was operated at a rotational speed of 3000-4500 rpm and a mean pump flow of 3.2 ± 0.6 L min. Excess hemolysis, observed in one goat, was due to the inadequate increase in pump rotational speed in response to drainage insufficiency caused by continuous contact of the inflow cannula tip with the left ventricular septal wall in the early days after surgery. At necropsy, no thrombus was noted in the pump, and no damage caused by mechanical contact was found on the bearing. The newly developed temporary left ventricular assist system using a disposable centrifugal pump with hydrodynamic bearing demonstrated consistent and satisfactory hemodynamic performance and hemocompatibility in the goat model.

  4. Teddy Bear Stories

    DEFF Research Database (Denmark)

    van Leeuwen, Theo; Caldas-Coulthardt, Carmen

    2014-01-01

    This paper presents a semiotic analysis of a key cultural artefact, the teddy bear. After introducing the iconography of the teddy bear, it analyses different kinds of stories to show how teddy bears are endowed with meaning in everyday life: stories from children's books, reminiscenses by adults...... about their childhood teddy bears, and children's accounts of what they do with teddy bears, both written for school and told 'out of school', The chapter sees teddy bears as artefacts that provide a cultural channeling for the child's need of a transitional object and argues that the meanings of teddy...... bears have traditionally centred on interpersonal relations within the nuclear family, but have recently been institutionalized and commercialized....

  5. Network models of TEM β-lactamase mutations coevolving under antibiotic selection show modular structure and anticipate evolutionary trajectories.

    Science.gov (United States)

    Guthrie, Violeta Beleva; Allen, Jennifer; Camps, Manel; Karchin, Rachel

    2011-09-01

    Understanding how novel functions evolve (genetic adaptation) is a critical goal of evolutionary biology. Among asexual organisms, genetic adaptation involves multiple mutations that frequently interact in a non-linear fashion (epistasis). Non-linear interactions pose a formidable challenge for the computational prediction of mutation effects. Here we use the recent evolution of β-lactamase under antibiotic selection as a model for genetic adaptation. We build a network of coevolving residues (possible functional interactions), in which nodes are mutant residue positions and links represent two positions found mutated together in the same sequence. Most often these pairs occur in the setting of more complex mutants. Focusing on extended-spectrum resistant sequences, we use network-theoretical tools to identify triple mutant trajectories of likely special significance for adaptation. We extrapolate evolutionary paths (n = 3) that increase resistance and that are longer than the units used to build the network (n = 2). These paths consist of a limited number of residue positions and are enriched for known triple mutant combinations that increase cefotaxime resistance. We find that the pairs of residues used to build the network frequently decrease resistance compared to their corresponding singlets. This is a surprising result, given that their coevolution suggests a selective advantage. Thus, β-lactamase adaptation is highly epistatic. Our method can identify triplets that increase resistance despite the underlying rugged fitness landscape and has the unique ability to make predictions by placing each mutant residue position in its functional context. Our approach requires only sequence information, sufficient genetic diversity, and discrete selective pressures. Thus, it can be used to analyze recent evolutionary events, where coevolution analysis methods that use phylogeny or statistical coupling are not possible. Improving our ability to assess

  6. A transgenic mouse model of OI type V supports a neomorphic mechanism of the IFITM5 mutation.

    Science.gov (United States)

    Lietman, Caressa D; Marom, Ronit; Munivez, Elda; Bertin, Terry K; Jiang, Ming-Ming; Chen, Yuqing; Dawson, Brian; Weis, Mary Ann; Eyre, David; Lee, Brendan

    2015-03-01

    Osteogenesis imperfecta (OI) type V is characterized by increased bone fragility, long bone deformities, hyperplastic callus formation, and calcification of interosseous membranes. It is caused by a recurrent mutation in the 5' UTR of the IFITM5 gene (c.-14C > T). This mutation introduces an alternative start codon, adding 5 amino acid residues to the N-terminus of the protein. The mechanism whereby this novel IFITM5 protein causes OI type V is yet to be defined. To address this, we created transgenic mice expressing either the wild-type or the OI type V mutant IFITM5 under the control of an osteoblast-specific Col1a1 2.3-kb promoter. These mutant IFITM5 transgenic mice exhibited perinatal lethality, whereas wild-type IFITM5 transgenic mice showed normal growth and development. Skeletal preparations and radiographs performed on E15.5 and E18.5 OI type V transgenic embryos revealed delayed/abnormal mineralization and skeletal defects, including abnormal rib cage formation, long bone deformities, and fractures. Primary osteoblast cultures, derived from mutant mice calvaria at E18.5, showed decreased mineralization by Alizarin red staining, and RNA isolated from calvaria showed reduced expression of osteoblast differentiation markers such as Osteocalcin, compared with nontransgenic littermates and wild-type mice calvaria, consistent with the in vivo phenotype. Importantly, overexpression of wild-type Ifitm5 did not manifest a significant bone phenotype. Collectively, our results suggest that expression of mutant IFITM5 causes abnormal skeletal development, low bone mass, and abnormal osteoblast differentiation. Given that neither overexpression of the wild-type Ifitm5, as shown in our model, nor knock-out of Ifitm5, as previously published, showed significant bone abnormalities, we conclude that the IFITM5 mutation in OI type V acts in a neomorphic fashion. © 2014 American Society for Bone and Mineral Research.

  7. Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model.

    Science.gov (United States)

    Huang, Feng-Yun J; Lee, Te-Wei; Chang, Chih-Hsien; Chen, Liang-Cheng; Hsu, Wei-Hsin; Chang, Chien-Wen; Lo, Jem-Mau

    2015-01-01

    In this study, the (188)Re-labeled PEGylated nanoliposome ((188)Re-liposome) was prepared and evaluated as a therapeutic agent for glioma. The reporter cell line, F98(luc) was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of (188)Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered (188)Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the (188)Re-liposome-treated rats. By using bioluminescent imaging, the well-established reporter cell line (F98(luc)) showed a high relationship between cell number and its bioluminescent intensity (R(2)=0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of (188)Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the (188)Re-liposome-treated group than the control group (P<0.05). As a result, the lifespan of glioma-bearing rats treated with (188)Re-liposome was prolonged 10.67% compared to the control group. The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting (188)Re-liposome via systemic administration can significantly prolong the lifespan of orthotopic glioma-bearing

  8. Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

    Directory of Open Access Journals (Sweden)

    Huang FYJ

    2015-01-01

    Full Text Available Feng-Yun J Huang,1 Te-Wei Lee,2 Chih-Hsien Chang,2 Liang-Cheng Chen,2 Wei-Hsin Hsu,2 Chien-Wen Chang,1 Jem-Mau Lo1 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan; 2Institute of Nuclear Energy Research, Longtan, Taiwan Purpose: In this study, the 188Re-labeled PEGylated nanoliposome (188Re-liposome was prepared and evaluated as a therapeutic agent for glioma.Materials and methods: The reporter cell line, F98luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188Re-liposome-treated rats.Results: By using bioluminescent imaging, the well-established reporter cell line (F98luc showed a high relationship between cell number and its bioluminescent intensity (R2=0.99 in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188Re-liposome-treated group than the control group (P<0.05. As a result, the

  9. Secondary and tertiary structure modeling reveals effects of novel mutations in polycystic liver disease genes PRKCSH and SEC63.

    NARCIS (Netherlands)

    Waanders, E.; Venselaar, H.; Morsche, R.H.M. te; Koning, D.B. de; Kamath, P.S.; Torres, V.E.; Somlo, S.; Drenth, J.P.H.

    2010-01-01

    Polycystic liver disease (PCLD) is characterized by intralobular bile duct cysts in the liver. It is caused by mutations in PRKCSH, encoding hepatocystin, and SEC63, encoding Sec63p. The main goals of this study were to screen for novel mutations and to analyze mutations for effects on protein

  10. Rotor Vibration Reduction via Active Hybrid Bearings

    DEFF Research Database (Denmark)

    Nicoletti, Rodrigo; Santos, Ilmar

    2002-01-01

    orifices machined in the bearing pads, one can alter the machine dynamic characteristics, thus enhancing its operational range. A mathematical model of the rotor-bearing system, as well as of the hydraulic system, is presented. Numerical results of the system frequency response show good agreement...

  11. Mutation identification in a canine model of X-linked ectodermal dysplasia.

    Science.gov (United States)

    Casal, Margret L; Scheidt, Jennifer L; Rhodes, James L; Henthorn, Paula S; Werner, Petra

    2005-07-01

    X-linked hypohidrotic ectodermal dysplasia (XHED), an inherited disease recognized in humans, mice, and cattle, is characterized by hypotrichosis, a reduced number or absence of sweat glands, and missing or malformed teeth. In a subset of affected individuals and animals, mutations in the EDA gene (formerly EDI), coding for ectodysplasin, have been found to cause this phenotype. Ectodysplasin is a homotrimeric transmembrane protein with an extracellular TNF-like domain, which has been shown to be involved in the morphogenesis of hair follicles and tooth buds during fetal development. Some human XHED patients also have concurrent immunodeficiency, due to mutations in the NF-kappaB essential modulator protein (IKBKG; formerly NEMO), which is also encoded on the X chromosome. In a breeding colony of dogs with XHED, immune system defects had been suspected because of frequent pulmonary infections and unexpected deaths resulting from pneumonia. To determine if defects in EDA or IKBKG cause XHED in the dogs, linkage analysis and sequencing experiments were performed. A polymorphic marker near the canine EDA gene showed significant linkage to XHED. The canine EDA gene was sequenced and a nucleotide substitution (G to A) in the splice acceptor site of intron 8 was detected in affected dogs. In the presence of the A residue, a cryptic acceptor site within exon 9 is used, leading to a frame shift and use of a premature stop codon that truncates the translation of both isoforms, EDA-A1 and EDA-A2, resulting in the absence of the TNF-like homology domain, the receptor-binding site of ectodysplasin.

  12. Mechanical characterization of structurally porous biomaterials built via additive manufacturing: experiments, predictive models, and design maps for load-bearing bone replacement implants.

    Science.gov (United States)

    Melancon, D; Bagheri, Z S; Johnston, R B; Liu, L; Tanzer, M; Pasini, D

    2017-11-01

    Porous biomaterials can be additively manufactured with micro-architecture tailored to satisfy the stringent mechano-biological requirements imposed by bone replacement implants. In a previous investigation, we introduced structurally porous biomaterials, featuring strength five times stronger than commercially available porous materials, and confirmed their bone ingrowth capability in an in vivo canine model. While encouraging, the manufactured biomaterials showed geometric mismatches between their internal porous architecture and that of its as-designed counterpart, as well as discrepancies between predicted and tested mechanical properties, issues not fully elucidated. In this work, we propose a systematic approach integrating computed tomography, mechanical testing, and statistical analysis of geometric imperfections to generate statistical based numerical models of high-strength additively manufactured porous biomaterials. The method is used to develop morphology and mechanical maps that illustrate the role played by pore size, porosity, strut thickness, and topology on the relations governing their elastic modulus and compressive yield strength. Overall, there are mismatches between the mechanical properties of ideal-geometry models and as-manufactured porous biomaterials with average errors of 49% and 41% respectively for compressive elastic modulus and yield strength. The proposed methodology gives more accurate predictions for the compressive stiffness and the compressive strength properties with a reduction of the average error to 11% and 7.6%. The implications of the results and the methodology here introduced are discussed in the relevant biomechanical and clinical context, with insight that highlights promises and limitations of additively manufactured porous biomaterials for load-bearing bone replacement implants. In this work, we perform mechanical characterization of load-bearing porous biomaterials for bone replacement over their entire design

  13. Mammographic screening in BRCA1 mutation carriers postponed until age 40: Evaluation of benefits, costs and radiation risks using models.

    Science.gov (United States)

    Obdeijn, Inge-Marie; Heijnsdijk, Eveline A M; Hunink, M G Myriam; Tilanus-Linthorst, Madeleine M A; de Koning, Harry J

    2016-08-01

    BRCA1 mutation carriers are offered screening with magnetic resonance imaging (MRI) and mammography. The aim of this study was to weigh benefits and risks of postponing mammographic screening until age 40. With the MISCAN microsimulation model two screening protocols were evaluated: 1) the current Dutch guidelines: annual MRI from age 25-60, annual mammography from age 30-60, and biennial mammography in the nationwide program from age 60-74, and 2) the modified protocol: with annual mammography postponed until age 40. A cost-effectiveness analysis was performed. The risks of radiation-induced breast cancer mortality were estimated with absolute and relative exposure-risk models of the 7th Biological Effects of Ionising Radiation Committee. Current screening guidelines prevent 13,139 breast cancer deaths per 100,000 BRCA1 mutation carriers. Postponing mammography until age 40 would increase breast cancer deaths by 23 (0.17%), but would also reduce radiation-induced breast cancer deaths by 15 or 105 using the absolute and relative risk model respectively per 100,000 women screened. The estimated net effect is an increase of eight or a reduction of 82 breast cancer deaths per 100,000 women screened (depending on the risk model used). The incremental cost of mammograms between age 30-39 is €272,900 per life year gained. The modified protocol may be slightly less effective or even better than the current guidelines. The high cost-savings justify a possible small loss of effectiveness. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Effect of Interferon-γ on the Basal and the TNFα-Stimulated Secretion of CXCL8 in Thyroid Cancer Cell Lines Bearing Either the RET/PTC Rearrangement Or the BRAF V600e Mutation

    Directory of Open Access Journals (Sweden)

    Mario Rotondi

    2016-01-01

    Full Text Available CXCL8 displays several tumor-promoting effects. Targeting and/or lowering CXCL8 concentrations within the tumor microenvironment would produce a therapeutic benefit. Aim of this study was to test the effect of IFNγ on the basal and TNFα-stimulated secretion of CXCL8 in TCP-1 and BCPAP thyroid cancer cell lines (harboring RET/PTC rearrangement and BRAF V600e mutation, resp.. Cells were incubated with IFNγ (1, 10, 100, and 1000 U/mL alone or in combination with TNF-α (10 ng/mL for 24 hours. CXCL8 and CXCL10 concentrations were measured in the cell supernatants. IFNγ inhibited in a dose-dependent and significant manner both the basal (ANOVA F: 22.759; p<0.00001 and the TNFα-stimulated (ANOVA F: 15.309; p<0.00001 CXCL8 secretions in BCPAP but not in TPC-1 cells (NS. On the other hand, IFNγ and IFNγ + TNF-α induced a significant secretion of CXCL10 in both BCPAP (p<0.05 and TPC-1 (p<0.05 cells. Transwell migration assay showed that (i CXCL8 increased cell migration in both TPC-1 and BCPAP cells; (ii IFNγ significantly reduced the migration only of BCPAP cells; and (iii CXCL8 reverted the effect of IFNγ. These results constitute the first demonstration that IFNγ inhibits CXCL8 secretion and in turn the migration of a BRAF V600e mutated thyroid cell line.

  15. Bearings: Technology and needs

    Science.gov (United States)

    Anderson, W. J.

    1982-01-01

    A brief status report on bearing technology and present and near-term future problems that warrant research support is presented. For rolling element bearings a material with improved fracture toughness, life data in the low Lambda region, a comprehensive failure theory verified by life data and incorporated into dynamic analyses, and an improved corrosion resistant alloy are perceived as important needs. For hydrodynamic bearings better definition of cavitation boundaries and pressure distributions for squeeze film dampers, and geometry optimization for minimum power loss in turbulent film bearings are needed. For gas film bearings, foil bearing geometries that form more nearly optimum film shapes for maximum load capacity, and more effective surface protective coatings for high temperature operation are needed.

  16. Polar bears, Ursus maritimus

    Science.gov (United States)

    Rode, Karyn D.; Stirling, Ian

    2017-01-01

    Polar bears are the largest of the eight species of bears found worldwide and are covered in a pigment-free fur giving them the appearance of being white. They are the most carnivorous of bear species consuming a high-fat diet, primarily of ice-associated seals and other marine mammals. They range throughout the circumpolar Arctic to the southernmost extent of seasonal pack ice.

  17. EcoBears

    DEFF Research Database (Denmark)

    Nielsen, Nick; Pedersen, Sandra Bleuenn; Sørensen, Jens Ager

    2015-01-01

    In this paper, we introduce the EcoBears concept that aims to augment household appliances with functional and aesthetic features to promote their "use'' and "longevity of use'' to prevent their disposal. The EcoBears also aim to support the communication of environmental issues in the home setting....... We present our initial design and implementation of the EcoBears that consist of two bear modules (a mother and her cub). We also present our preliminary concept validations and lessons learned to be considered for future directions....

  18. Intratumoral distribution of {sup 64}Cu-ATSM and {sup 18}F-FDG in VX2 tumor bearing rabbit model

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Ran Ji; Lee, Yong Jin; Lee, Won Ho; Kim, Kyeong Min; Park, Ji Ae; Lee, Kyo Chul; Chung, Wee Sup; Kang, Joo Hyun; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2012-05-15

    Imaging acquisition and analysis of hypoxic region within solid tumor is essential for understanding the microenvironment of tumor, and is also important for the establishment of proper therapeutic strategy and evaluation for radiation therapy (1-5). {sup 64}Cu-labeled diacetyl-bis (N{sub 4}-methylthiosemicarbazone) ({sup 64}Cu-ATSM) is a promising agent for imaging of hypoxic tissues and internal radiation therapy for tumor. In this study, we obtained PET/CT images of tumor using {sup 64}Cu-ATSM and {sup 18}F-FDG, and then evaluated the distribution of hypoxic region after comparing with oxygen partial pressure in VX2 tumor bearing rabbit model. MR images are also obtained for precise anatomical information

  19. Unbalanced Magnetic Pull Effect on Stiffness Models of Active Magnetic Bearing due to Rotor Eccentricity in Brushless DC Motor Using Finite Element Method

    Directory of Open Access Journals (Sweden)

    Bangcheng Han

    2013-01-01

    Full Text Available We firstly report on an investigation into the unbalanced magnetic pull (UMP effect on the static stiffness models of radial active magnetic bearing (RAMB in brushless DC motor (BDCM in no-loaded and loaded conditions using the finite element method (FEM. The influences of the UMP on the force-control current, force-position, current stiffness, and position stiffness of RAMB are clarified in BDCM with 100 kW rated power. We found the position stiffness to be more susceptible to UMP. The primary source of UMP is the permanent magnets of BDCM. In addition, the performance of RAMB is affected by the UMP ripples during motor commutation and also periodically affected by the angular position of rotor. The characteristic curves of RAMB force versus control current (or rotor position and angular position of rotor affected by the UMP are given. The method is useful in design and optimization of RAMB in magnetically suspended BDCMs.

  20. Origin of peak and retrograde assemblages during Grenvillian orogeny from garnet-staurolite bearing mica schist of Bhilwara Supergroup, NW India: constraints from pseudosection modelling

    Science.gov (United States)

    Prakash, Abhishek; Saha, Lopamudra; Sarkar, Saheli

    2016-04-01

    Fractionation of components due to formation of garnet porphyroblasts during prograde metamorphism, have been constrained from pseudosection analyses. Such fractionation process leads to changes in the effective bulk composition within the rock, which can be modelled with well-preserved growth zonation patterns in garnet porphyroblasts. On the contrary, textures and mineralogy in metamorphic rocks can be far more complex with different textural domains within a single rock preserving assemblages formed along different segments of the P-T paths or during different metamorphic events. Examples of such textures include pseudomorphs, reaction rims or coronae, symplectites formed by breakdown of both cores and rims of porphyroblasts. Apart from pressure and temperature, availability of fluids during metamorphic reactions plays important roles in defining mineral assemblages and textures. In this study we have constrained formation of garnet porphyroblasts and paragonite-albite-sillimanite-quartz-staurolite bearing domains within the mica schist from the Rajpura-Dariba sequence of the Bhilwara Supergroup in NW India. The mica schist is inter-layered with calc-silicates and quartzite and together the units form a NE-SW trending Grenvillian orogenic belt in southern part of Bhilwara Supergroup sequence. Within the mica schist, three distinct textural domains have been observed: (i) muscovite-biotite-quartz-feldspar bearing matrix foliation, (ii) garnet porphyroblasts within the matrix foliation, (iii) staurolite-paragonite-albite-staurolite-sillimanite-quartz bearing domains. Paragonite, albite and sillimanite occur exclusively in the pseudomorph domains. Garnet porphyroblasts show variation in compositions from cores (Spessartine0.14 Grossular0.10 Pyrope0.12 Almandine0.72) to rims (Spessartine0.09Grossular0.15Pyrope0.12Almandine0.75). The average XMg contents of staurolite and matrix biotite are 0.21 and 0.57 respectively. Pseudosections have been constructed from the

  1. Thermohydrodynamic analysis of cryogenic liquid turbulent flow fluid film bearings

    Science.gov (United States)

    Andres, Luis San

    1993-01-01

    A thermohydrodynamic analysis is presented and a computer code developed for prediction of the static and dynamic force response of hydrostatic journal bearings (HJB's), annular seals or damper bearing seals, and fixed arc pad bearings for cryogenic liquid applications. The study includes the most important flow characteristics found in cryogenic fluid film bearings such as flow turbulence, fluid inertia, liquid compressibility and thermal effects. The analysis and computational model devised allow the determination of the flow field in cryogenic fluid film bearings along with the dynamic force coefficients for rotor-bearing stability analysis.

  2. Evolution models with lethal mutations on symmetric or random fitness landscapes.

    Science.gov (United States)

    Kirakosyan, Zara; Saakian, David B; Hu, Chin-Kun

    2010-07-01

    We calculate the mean fitness for evolution models, when the fitness is a function of the Hamming distance from a reference sequence, and there is a probability that this fitness is nullified (Eigen model case) or tends to the negative infinity (Crow-Kimura model case). We calculate the mean fitness of these models. The mean fitness is calculated also for the random fitnesses with logarithmic-normal distribution, reasonably describing sometimes the situation with RNA viruses.

  3. Computational analysis of the human sinus node action potential: model development and effects of mutations

    NARCIS (Netherlands)

    Fabbri, Alan; Fantini, Matteo; Wilders, Ronald; Severi, Stefano

    2017-01-01

    We constructed a comprehensive mathematical model of the spontaneous electrical activity of a human sinoatrial node (SAN) pacemaker cell, starting from the recent Severi-DiFrancesco model of rabbit SAN cells. Our model is based on electrophysiological data from isolated human SAN pacemaker cells and

  4. Small-scale modelling of cementation by descending silica-bearing fluids: Explanation of the origin of arenitic caves in South American tepuis

    Science.gov (United States)

    Aubrecht, R.; Lánczos, T.; Schlögl, J.; Audy, M.

    2017-12-01

    Geoscientific research was performed on South American table mountains (tepuis) and in their sandstone cave systems. To explain speleogenesis in these poorly soluble rocks, two theories were introduced: a) arenization theory implying selective weathering of quartz along grain boundaries and releasing of sand grains, b) selective lithification theory implying cementation by descending silica-bearing fluid flow. The latter theory presumes that the descending fluid flow becomes unstable on the interface between two layers with different porosity and splits to separate flow channels (so-called ;finger flow;). The arenites outside these channels remain uncemented. To verify the latter theory, small-scale modelling was performed, using layered sands and sodium-silicate solution. Fine to medium sand was used (0.08-0.5 mm), along with a coarse sand fraction (0.5-1.5 mm). The sands were layered and compacted in a transparent plastic boxes. Three liters of sodium-silicate solution (so-called water glass) were left to drip for several hours to the top of the sediment. The fine-grained layers were perfectly laterally impregnated, whereas the descending fluid flows split to ;fingers; in the coarse-grained layers due their higher hydraulic conductivity. This small-scale laboratory simulation mimics the real diagenesis by descending silica-bearing fluids and matches the real phenomena observed on the tepuis. The resulting cemented constructions closely mimic many geomorphological features observed on tepuis and inside their caves, e.g. ;finger-flow; pillars, overhangs, imperfectly formed (aborted) pillars in forms of hummocks hanging from ceilings, locally also thicker central pillars that originated by merging of smaller fluid-flow channels. The modelling showed that selective lithification theory can explain most of the geomorphological aspects related to the speleogenesis in tepuis.

  5. Preappointment testing for BRAF/KIT mutation in advanced melanoma: a model in molecular data delivery for individualized medicine.

    Science.gov (United States)

    Mounajjed, Taofic; Brown, Char L; Stern, Therese K; Bjorheim, Annette M; Bridgeman, Andrew J; Rumilla, Kandelaria M; McWilliams, Robert R; Flotte, Thomas J

    2014-11-01

    The emergence of individualized medicine is driven by developments in precision diagnostics, epitomized by molecular testing. Because treatment decisions are being made based on such molecular data, data management is gaining major importance. Among data management challenges, creating workflow solutions for timely delivery of molecular data has become pivotal. This study aims to design and implement a scalable process that permits preappointment BRAF/KIT mutation analysis in melanoma patients, allowing molecular results necessary for treatment plans to be available before the patient's appointment. Process implementation aims to provide a model for efficient molecular data delivery for individualized medicine. We examined the existing process of BRAF/KIT testing in melanoma patients visiting our institution for oncology consultation. We created 5 working groups, each designing a specific segment of an alternative process that would allow preappointment BRAF/KIT testing and delivery of results. Data were captured and analyzed to evaluate the success of the alternative process. For 1 year, 35 (59%) of 55 patients had prior BRAF/KIT testing. The remaining 20 patients went through the new process of preappointment testing; results were available at the time of appointment for 12 patients (overall preappointment results availability, 85.5%). The overall process averaged 13.4 ± 4.7 days. In conclusion, we describe the successful implementation of a scalable workflow solution that permits preappointment BRAF/KIT mutation analysis and result delivery in melanoma patients. This sets the stage for further applications of this model to other conditions, answering an increasing demand for robust delivery of molecular data for individualized medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. RNA interference gene therapy in dominant retinitis pigmentosa and cone-rod dystrophy mouse models caused by GCAP1 mutations

    Directory of Open Access Journals (Sweden)

    Li eJiang

    2014-04-01

    Full Text Available RNA interference (RNAi knockdown is an efficacious therapeutic strategy for silencing genes causative for dominant retinal dystrophies. To test this, we used self-complementary (sc AAV2/8 vector to develop an RNAi-based therapy in two dominant retinal degeneration mouse models. The allele-specific model expresses transgenic bovine GCAP1(Y99C establishing a rapid RP-like phenotype, whereas the nonallele-specific model expresses mouse GCAP1(L151F producing a slowly progressing cone/rod dystrophy (CORD. The late onset GCAP1(L151F-CORD mimics the dystrophy observed in human GCAP1-CORD patients. Subretinal injection of scAAV2/8 carrying shRNA expression cassettes specific for bovine or mouse GCAP1 showed strong expression at one week post-injection. In both allele-specific (GCAP1(Y99C-RP and nonallele-specific (GCAP1(L151F-CORD models of dominant retinal dystrophy, RNAi-mediated gene silencing enhanced photoreceptor survival, delayed onset of degeneration and improved visual function. Such results provide a proof of concept toward effective RNAi-based gene therapy mediated by scAAV2/8 for dominant retinal disease based on GCAP1 mutation. Further, nonallele-specific RNAi knockdown of GCAP1 may prove generally applicable toward the rescue of any human GCAP1-based dominant cone-rod dystrophy.

  7. Radon-induced lung cancer in smokers and non-smokers: risk implications using a two-mutation carcinogenesis model

    International Nuclear Information System (INIS)

    Leenhouts, H.P.

    1999-01-01

    Three sets of data (population statistics in non-smokers, data from an investigation of the smoking habits of British doctors and a study of Colorado uranium miners) were used to analyse lung cancer in humans as a function of exposure to radon and smoking. One of the aims was to derive implications for radon risk estimates. The data were analysed using a two-mutation radiation carcinogenesis model and a stepwise determination of the model parameters. The basic model parameters for lung cancer were derived from the age dependence fit of the spontaneous lung cancer incidence in non-smokers. The effect of smoking was described by two additional parameters and, subsequently, the effect of radon by three other parameters; these five parameters define the dependence of the two mutation steps on smoking and exposure to radon. Using this approach, a consistent fit and comprehensive description of the three sets of data have been achieved, and the parameters could, at least partly, be related to cellular radiobiological data. The model results explain the different effect of radon on non-smokers and smokers as seen in epidemiological data. Although the analysis was only applied to a limited number of populations, lung cancer incidence as a result of radon exposure is estimated to be about ten times higher for people exposed at the age of about 15 than at about 50, although this effect is masked (especially for smokers) by the high lung cancer incidence from smoking. Using the model to calculate the lung cancer risks from lifetime exposure to radon, as is the case for indoor radon, higher risks were estimated than previously derived from epidemiological studies of the miners' data. The excess absolute risk per unit exposure of radon is about 1.7 times higher for smokers of 30 cigarettes per day than for non-smokers, even though, as a result of the low spontaneous tumour incidence in the non-smokers, the excess relative risk per unit exposure for the smokers is about 20 times

  8. Biochemical evidence for a mitochondrial genetic modifier in the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation.

    Science.gov (United States)

    Jiang, Pingping; Liang, Min; Zhang, Chaofan; Zhao, Xiaoxu; He, Qiufen; Cui, Limei; Liu, Xiaoling; Sun, Yan-Hong; Fu, Qun; Ji, Yanchun; Bai, Yidong; Huang, Taosheng; Guan, Min-Xin

    2016-08-15

    Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disease. Mitochondrial modifiers are proposed to modify the phenotypic expression of primary LHON-associated mitochondrial DNA (mtDNA) mutations. In this study, we demonstrated that the LHON susceptibility allele (m.14502T > C, p. 58I > V) in the ND6 gene modulated the phenotypic expression of primary LHON-associated m.11778G > A mutation. Twenty-two Han Chinese pedigrees carrying m.14502T > C and m.11778G > A mutations exhibited significantly higher penetrance of optic neuropathy than those carrying only m.11778G > A mutation. We performed functional assays using the cybrid cell models, generated by fusing mtDNA-less ρ o cells with enucleated cells from LHON patients carrying both m.11778G > A and m.14502T > C mutations, only m.14502T > C or m.11778G > A mutation and a control belonging to the same mtDNA haplogroup. These cybrids cell lines bearing m.14502T > C mutation exhibited mild effects on mitochondrial functions compared with those carrying only m.11778G > A mutation. However, more severe mitochondrial dysfunctions were observed in cell lines bearing both m.14502T > C and m.11778G > A mutations than those carrying only m.11778G > A or m.14502T > C mutation. In particular, the m.14502T > C mutation altered assemble of complex I, thereby aggravating the respiratory phenotypes associated with m.11778G > A mutation, resulted in a more defective complex I. Furthermore, more reductions in the levels of mitochondrial ATP and increasing production of reactive oxygen species were also observed in mutant cells bearing both m.14502T > C and m.11778G > A mutation than those carrying only 11778G > A mutation. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between primary and secondary mtDNA mutations. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Insights into the latent multinomial model through mark-resight data on female grizzly bears with cubs-of-the-year

    Science.gov (United States)

    Higgs, Megan D.; Link, William; White, Gary C.; Haroldson, Mark A.; Bjornlie, Daniel D.

    2013-01-01

    Mark-resight designs for estimation of population abundance are common and attractive to researchers. However, inference from such designs is very limited when faced with sparse data, either from a low number of marked animals, a low probability of detection, or both. In the Greater Yellowstone Ecosystem, yearly mark-resight data are collected for female grizzly bears with cubs-of-the-year (FCOY), and inference suffers from both limitations. To overcome difficulties due to sparseness, we assume homogeneity in sighting probabilities over 16 years of bi-annual aerial surveys. We model counts of marked and unmarked animals as multinomial random variables, using the capture frequencies of marked animals for inference about the latent multinomial frequencies for unmarked animals. We discuss undesirable behavior of the commonly used discrete uniform prior distribution on the population size parameter and provide OpenBUGS code for fitting such models. The application provides valuable insights into subtleties of implementing Bayesian inference for latent multinomial models. We tie the discussion to our application, though the insights are broadly useful for applications of the latent multinomial model.

  10. The role of human outdoor recreation in shaping patterns of grizzly bear-black bear co-occurrence.

    Directory of Open Access Journals (Sweden)

    Andrew Ladle

    Full Text Available Species' distributions are influenced by a combination of landscape variables and biotic interactions with other species, including people. Grizzly bears and black bears are sympatric, competing omnivores that also share habitats with human recreationists. By adapting models for multi-species occupancy analysis, we analyzed trail camera data from 192 trail camera locations in and around Jasper National Park, Canada to estimate grizzly bear and black bear occurrence and intensity of trail use. We documented (a occurrence of grizzly bears and black bears relative to habitat variables (b occurrence and intensity of use relative to competing bear species and motorised and non-motorised recreational activity, and (c temporal overlap in activity patterns among the two bear species and recreationists. Grizzly bears were spatially separated from black bears, selecting higher elevations and locations farther from roads. Both species co-occurred with motorised and non-motorised recreation, however, grizzly bears reduced their intensity of use of sites with motorised recreation present. Black bears showed higher temporal activity overlap with recreational activity than grizzly bears, however differences in bear daily activity patterns between sites with and without motorised and non-motorised recreation were not significant. Reduced intensity of use by grizzly bears of sites where motorised recreation was present is a concern given off-road recreation is becoming increasingly popular in North America, and can negatively influence grizzly bear recovery by reducing foraging opportunities near or on trails. Camera traps and multi-species occurrence models offer non-invasive methods for identifying how habitat use by animals changes relative to sympatric species, including humans. These conclusions emphasise the need for integrated land-use planning, access management, and grizzly bear conservation efforts to consider the implications of continued access for

  11. The role of human outdoor recreation in shaping patterns of grizzly bear-black bear co-occurrence.

    Science.gov (United States)

    Ladle, Andrew; Steenweg, Robin; Shepherd, Brenda; Boyce, Mark S

    2018-01-01

    Species' distributions are influenced by a combination of landscape variables and biotic interactions with other species, including people. Grizzly bears and black bears are sympatric, competing omnivores that also share habitats with human recreationists. By adapting models for multi-species occupancy analysis, we analyzed trail camera data from 192 trail camera locations in and around Jasper National Park, Canada to estimate grizzly bear and black bear occurrence and intensity of trail use. We documented (a) occurrence of grizzly bears and black bears relative to habitat variables (b) occurrence and intensity of use relative to competing bear species and motorised and non-motorised recreational activity, and (c) temporal overlap in activity patterns among the two bear species and recreationists. Grizzly bears were spatially separated from black bears, selecting higher elevations and locations farther from roads. Both species co-occurred with motorised and non-motorised recreation, however, grizzly bears reduced their intensity of use of sites with motorised recreation present. Black bears showed higher temporal activity overlap with recreational activity than grizzly bears, however differences in bear daily activity patterns between sites with and without motorised and non-motorised recreation were not significant. Reduced intensity of use by grizzly bears of sites where motorised recreation was present is a concern given off-road recreation is becoming increasingly popular in North America, and can negatively influence grizzly bear recovery by reducing foraging opportunities near or on trails. Camera traps and multi-species occurrence models offer non-invasive methods for identifying how habitat use by animals changes relative to sympatric species, including humans. These conclusions emphasise the need for integrated land-use planning, access management, and grizzly bear conservation efforts to consider the implications of continued access for motorised

  12. On Controllable Elastohydrodynamic Fluid Film Bearings

    DEFF Research Database (Denmark)

    Haugaard, Martin Asger

    This thesis gives a theoretical description of the active tilting-pad journal bearing (ATPJB). It provides the qualified reader with the tools to model an ATPJB, while staying clear of pitfalls. The model is based on well known techniques and allows for local stability analyses, harmonic stationary...... are performed for a tilting-pad journal bearing (TPJB) and an ATPJB under static conditions, followed by a generalisation to dynamic conditions (transient as well as stationary harmonic). These analyses will be of interest to experimentalists, since they permit experiments performed on scaled down test rigs...... the addition of a control system may just as well harm rotor-bearing performance as improve it....

  13. Rotational decay torques of superconducting magnetic bearing

    International Nuclear Information System (INIS)

    Takahata, R.; Yotsuya, T.

    1991-01-01

    This paper proposes a superconducting magnetic bearing as one of application of a high critical temperature (Tc) oxide superconducting material. The authors have assembled new models of bearing with free rotation axis. In these models, superconductor, YBa 2 Cu 3 O X , prepared by the quench and melt growth (QMG) method was applied to the bearing section and a permanent magnet was used for a rotor. This development originated from the knowledge that YBa 2 Cu 3 O X prepared by QMG method had a stronger pinning force of magnetic flux than that of conventional superconductors

  14. Why did the bear cross the road? Comparing the performance of multiple resistance surfaces and connectivity modeling methods

    Science.gov (United States)

    Samuel A. Cushman; Jesse S. Lewis; Erin L. Landguth

    2014-01-01

    There have been few assessments of the performance of alternative resistance surfaces, and little is known about how connectivity modeling approaches differ in their ability to predict organism movements. In this paper, we evaluate the performance of four connectivity modeling approaches applied to two resistance surfaces in predicting the locations of highway...

  15. Nonlinear electromagnetic effects on magnetic bearing performance and power loss

    Science.gov (United States)

    Kenny, Andrew

    Magnetic bearings are now being used in many applications. One of their features is their ability to apply force without contact. Thus they do not wear out from friction and are quiet. Magnetic bearings have very low levels of parasitic drag torque and force, especially at lower speeds. Active magnetic bearings can utilize microprocessors and feedback to control or excite vibrations in a manner that is unique from all other types of bearings. This dissertation presents methods to design magnetic bearings and makes some advances to them. The circuit model equations for a homopolar bearing are presented and a solution is found including the effects of magnetic flux saturation and laminate stacking. Circuit model equations for thrust bearings are presented. Linearized frequency dependent reluctance elements are incorporated into these equations. The equations are arranged to predict the frequency dependence of thrust bearings and the predictions agree with measurements. Finite element models are used extensively to back up the circuit model results. The drag torque caused by high rotation speed is calculated by the finite element method. The accuracy of these calculations is confirmed by comparison to measurements available in previously published experiments. Predictions of the drag torque in homopolar bearing rotor spacers are presented. The finite element method is also used to confirm the performance equations derived for a novel thrust bearing and a novel radial bearing, and it is also used to confirm the advanced circuit equations which are demonstrated on homopolar bearings.

  16. Trends in Controllable Oil Film Bearings

    DEFF Research Database (Denmark)

    Santos, Ilmar

    2011-01-01

    This work gives an overview about the theoretical and experimental achievements of mechatronics applied to oil film bearings, with the aim of: controlling the lateral vibration of flexible rotating shafts; modifying bearing dynamic characteristics, as stiffness and damping properties; increasing...... the rotational speed ranges by improving damping and eliminating instability problems, for example, by compensating cross-coupling destabilizing effects; reducing startup torque and energy dissipation in bearings; compensating thermal effects. It is shown that such controllable bearings can act as "smart......" components and be applied to rotating machines with the goal of avoiding unexpected stops of plants, performing rotordynamic tests and identifying model parameters "on site". Emphasis is given to the controllable lubrication (active lubrication) applied to different types of oil film bearings, i...

  17. Fluorine lubricated bearing technology

    Science.gov (United States)

    Mallaire, F. R.

    1973-01-01

    An experimental program was conducted to evaluate and select materials for ball bearings intended for use in liquid fluorine and/or FLOX. The ability of three different ball-separator materials, each containing nickel, to form and transfer a nickel fluoride film to provide effective lubrication at the required areas of a ball bearing operating in liquid fluorine was evaluated. In addition, solid lubrication of a ball bearing operating in liquid fluorine by either a fused fluoride coating applied to all surfaces of the ball separator or by a fluoride impregnation of porous sintered material ball separators was evaluated. Less bearing wear occurred when tests were conducted in the less reactive FLOX. Bearings fabricated from any of the materials tested would have relatively short wear lives and would require frequent replacement in a reusable engine.

  18. STAT3 mutations correlated with hyper-IgE syndrome lead to ...

    Indian Academy of Sciences (India)

    Using STAT3-null human colon carcinoma cell line A4 cells, we generated seven mutants of STAT3 bearing single mutations clinically identified in AD-HIES patients' cells and studied the functional loss of these mutants in IL-6-Jak/STAT3 signalling pathway. Our results show that five STAT3 mutants bearing mutations in the ...

  19. Modified effective medium model for gas hydrate bearing,clay-dominated sediments in the Krishna-Godavari Basin

    Digital Repository Service at National Institute of Oceanography (India)

    Sriram, G.; Dewangan, P.; Ramprasad, T.

    of unconsolidated marine sediments as well as with hydrate. In this paper, we study the friction-dependent effective medium model (EMM) to understand these grain interactions. The compressional (P) and shear (S) wave velocities of fluid saturated sediments...

  20. Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3

    Czech Academy of Sciences Publication Activity Database

    Christé, G.; Chahine, M.; Chevalier, P.; Pásek, Michal

    2008-01-01

    Roč. 96, - (2008), s. 281-293 ISSN 0079-6107 Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac cell * SCN5A mutation * Long QT syndrome * quantitative modelling Subject RIV: BO - Biophysics Impact factor: 6.388, year: 2008

  1. Discerning between recurrent gene flow and recent divergence under a finite-site mutation model applied to North Atlantic and Mediterranean Sea fin whale (Balaenoptera physalus) populations

    NARCIS (Netherlands)

    Palsboll, PJ; Berube, M; Aguilar, A; Notarbartolo-Di-Sciara, G; Nielsen, R

    Genetic divergence among conspecific subpopulations can be due to either low recurrent gene flow or recent divergence and no gene flow. Here we present a modification of an earlier method developed by Nielsen and Wakeley (2001), which accommodates a finite-site mutation model, to assess which of the

  2. Heuristic Value of a “Virtual Fruit” Model of Peach Fruit Quality and Sensitivity to Brown Rot : Impact of a Single Mutation and Design of Ideotypes

    OpenAIRE

    Génard, Michel; Quilot-Turion, Bénédicte; Ould Sidi, Mohamed Mahmoud; Kadrani, Abdeslam; Hilgert, Nadine; Lescourret, Francoise

    2015-01-01

    This work aimed at investigating the heuristic potential of a process-based model of peach fruit expressing seasonal changes in several quality attributes of fruit (e.g., size, percentages of flesh, water, sugar and acid contents) and fruit sensitivity to brown rot (skin density of cracks).[br/] Firstly, we showed that this “Virtual Fruit” could be used to analyze the impact of a single mutation which decreased the fruit’s requirement for carbon on peach fruit behavior. The mutation trigge...

  3. Research on Bored Bearing Characteristics in Xi’an

    Directory of Open Access Journals (Sweden)

    Zhang Lipeng

    2015-01-01

    Full Text Available To analyze the influence of different soil properties on pile foundation load-bearing characteristics, taking a section of railway in Xi’an and a bridge of Xi’an as test area, and by field static load test to study load transfer characteristics after the test piles under axial pressure, including the distribution of axial force, pile lateral friction, tip resistance traits, ultimate bearing capacity determine, and compare with the theory bearing capacity. Experimental results show that, adjacent soil properties change large, axial force and lateral friction mutation at the junction of corresponding soil layer. Silty clay in different parts is below ground, and its lateral friction plays much difference. Pile lateral friction plays an important role in bearing capacity, but the role of round gravel soil end bearing capacity to pile bearing capacity can’t be ignored. Tests calculate pile bearing capacity significantly larger than standardized formula calculation bearing capacity, which are respectively 55.35% and 119.1%. And give the similar project condition the suggested values of pile bearing capacity and soil friction, to provide reference for similar pile foundation design.

  4. Modeling sulfate reduction in methane hydrate-bearing continental margin sediments: Does a sulfate-methane transition require anaerobic oxidation of methane?

    Science.gov (United States)

    Malinverno, A.; Pohlman, J.W.

    2011-01-01

    The sulfate-methane transition (SMT), a biogeochemical zone where sulfate and methane are metabolized, is commonly observed at shallow depths (1-30 mbsf) in methane-bearing marine sediments. Two processes consume sulfate at and above the SMT, anaerobic oxidation of methane (AOM) and organoclastic sulfate reduction (OSR). Differentiating the relative contribution of each process is critical to estimate methane flux into the SMT, which, in turn, is necessary to predict deeper occurrences of gas hydrates in continental margin sediments. To evaluate the relative importance of these two sulfate reduction pathways, we developed a diagenetic model to compute the pore water concentrations of sulfate, methane, and dissolved inorganic carbon (DIC). By separately tracking DIC containing 12C and 13C, the model also computes ??13C-DIC values. The model reproduces common observations from methane-rich sediments: a well-defined SMT with no methane above and no sulfate below and a ??13C-DIC minimum at the SMT. The model also highlights the role of upward diffusing 13C-enriched DIC in contributing to the carbon isotope mass balance of DIC. A combination of OSR and AOM, each consuming similar amounts of sulfate, matches observations from Site U1325 (Integrated Ocean Drilling Program Expedition 311, northern Cascadia margin). Without AOM, methane diffuses above the SMT, which contradicts existing field data. The modeling results are generalized with a dimensional analysis to the range of SMT depths and sedimentation rates typical of continental margins. The modeling shows that AOM must be active to establish an SMT wherein methane is quantitatively consumed and the ??13C-DIC minimum occurs. The presence of an SMT generally requires active AOM. Copyright 2011 by the American Geophysical Union.

  5. The role of human outdoor recreation in shaping patterns of grizzly bear-black bear co-occurrence

    OpenAIRE

    Ladle, Andrew; Steenweg, Robin; Shepherd, Brenda; Boyce, Mark S.

    2018-01-01

    Species’ distributions are influenced by a combination of landscape variables and biotic interactions with other species, including people. Grizzly bears and black bears are sympatric, competing omnivores that also share habitats with human recreationists. By adapting models for multi-species occupancy analysis, we analyzed trail camera data from 192 trail camera locations in and around Jasper National Park, Canada to estimate grizzly bear and black bear occurrence and intensity of trail use....

  6. A double-layer structure model of uranium-bearing horizon in inland basins of medium to big size, North-west China, and its significance in metallogenic potential assessment

    International Nuclear Information System (INIS)

    Wang Zhilong.

    1985-01-01

    This paper presents a double-layer structure model of uranium-bearing horizon, i.e. uranium-bearing horizon = source rock (arkose red beds) + uranium trap (grey beds favourable to uranium precipitation) in inland basins of medium to big size, North-west China. The mechanism of its formation is: during diagenetic-epigenetic processes resulted in arkose red bed formation, feldspar was hydromicatized, feldspar and quartz were replaced by authigenic hematite, goethite and hydrogoethite and became red. In such oxidation process, part of uranium in detritus of silicates such as feldspar, quartz etc. was mobilized and released, but the released uranium can not be precipitated because of the oxidation environment, and it can be diffused during diagenetic dehydration and then precipitated in nearby grey beds with low Eh together with uranium-bearing 'stagnant water' fixed in pores, forming economic uranium concentration. It is evident that uranium deposit could not be formed owing to uranium dispersion in the case of absence of certain pervious grey beds rich in reductants, although arkose red beds could provide sufficient uranium source. Therefore, only the two conditions existed simultaneously, could the uranium-bearing horizons be formed. The significance of the model for uranium prospecting are as follows: 1. Uranium source range is much expanded concerning uranium prospecting in sandstone. Except the source in basement of the basin and its margins, we must also pay attention to the overlying red beds, especially the arkose red beds in inland basin of medium to big size. 2. For the potential assessment of basin and the selection of potential area, the model is an important prospecting criterion. 3. If we apply the main criterion uranium-bearing horizon-arkose red beds well, the buried ore bodies can be found provided that arkose red beds were regarded as a significant criterion of uranium-bearing horizon

  7. Development of hydrodynamic micro-bearings

    Science.gov (United States)

    Wang, P.; Zhang, J.; Spikes, H. A.; Reddyhoff, T.; Holmes, A. S.

    2016-11-01

    This paper describes the modelling and testing of mm-scale hydrodynamic bearings which are being developed to improve the efficiency of a cm-scale turbine energy harvester, whose efficiency was previously limited by poorly lubricated commercial jewel-bearings. The bearings were fabricated using DRIE and their performance was assessed using a custom built MEMS tribometer. Results demonstrate that acceptably low friction is achieved when low viscosity liquid lubricants are used in combination with an appropriate choice of friction modifier additive. Further reduction in friction is demonstrated when the step height of bearing is adjusted in accordance with hydrodynamic theory. In parallel with the experiments, hydrodynamic lubricant modelling has been carried out to predict and further optimize film thickness and friction performance. Modelling results are presented and validated against experimental friction data.

  8. The Tightness of the Kesten-Stigum Reconstruction Bound of Symmetric Model with Multiple Mutations

    Science.gov (United States)

    Liu, Wenjian; Jammalamadaka, Sreenivasa Rao; Ning, Ning

    2017-12-01

    It is well known that reconstruction problems, as the interdisciplinary subject, have been studied in numerous contexts including statistical physics, information theory and computational biology, to name a few. We consider a 2q-state symmetric model, with two categories of q states in each category, and 3 transition probabilities: the probability to remain in the same state, the probability to change states but remain in the same category, and the probability to change categories. We construct a nonlinear second-order dynamical system based on this model and show that the Kesten-Stigum reconstruction bound is not tight when q ≥ 4.

  9. Human SOD1 ALS Mutations in a Drosophila Knock-In Model Cause Severe Phenotypes and Reveal Dosage-Sensitive Gain- and Loss-of-Function Components.

    Science.gov (United States)

    Şahin, Aslı; Held, Aaron; Bredvik, Kirsten; Major, Paxton; Achilli, Toni-Marie; Kerson, Abigail G; Wharton, Kristi; Stilwell, Geoff; Reenan, Robert

    2017-02-01

    Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset motor neuron disease and familial forms can be caused by numerous dominant mutations of the copper-zinc superoxide dismutase 1 (SOD1) gene. Substantial efforts have been invested in studying SOD1-ALS transgenic animal models; yet, the molecular mechanisms by which ALS-mutant SOD1 protein acquires toxicity are not well understood. ALS-like phenotypes in animal models are highly dependent on transgene dosage. Thus, issues of whether the ALS-like phenotypes of these models stem from overexpression of mutant alleles or from aspects of the SOD1 mutation itself are not easily deconvolved. To address concerns about levels of mutant SOD1 in disease pathogenesis, we have genetically engineered four human ALS-causing SOD1 point mutations (G37R, H48R, H71Y, and G85R) into the endogenous locus of Drosophila SOD1 (dsod) via ends-out homologous recombination and analyzed the resulting molecular, biochemical, and behavioral phenotypes. Contrary to previous transgenic models, we have recapitulated ALS-like phenotypes without overexpression of the mutant protein. Drosophila carrying homozygous mutations rendering SOD1 protein enzymatically inactive (G85R, H48R, and H71Y) exhibited neurodegeneration, locomotor deficits, and shortened life span. The mutation retaining enzymatic activity (G37R) was phenotypically indistinguishable from controls. While the observed mutant dsod phenotypes were recessive, a gain-of-function component was uncovered through dosage studies and comparisons with age-matched dsod null animals, which failed to show severe locomotor defects or nerve degeneration. We conclude that the Drosophila knock-in model captures important aspects of human SOD1-based ALS and provides a powerful and useful tool for further genetic studies. Copyright © 2017 by the Genetics Society of America.

  10. Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with KitWv Mutations

    Directory of Open Access Journals (Sweden)

    Ayano Yurino

    2016-09-01

    Full Text Available In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous KitWv mutations into C57BL/6.Rag2nullIl2rgnull mice with NOD-Sirpa (BRGS strongly promoted human multi-lineage reconstitution. After xenotransplantation of human CD34+CD38− cord blood cells, these newly generated C57BL/6.Rag2nullIl2rgnullNOD-Sirpa KitWv/Wv (BRGSKWv/Wv mice showed significantly higher levels of human cell chimerism and long-term multi-lineage reconstitution compared with BRGS mice. Strikingly, this mouse displayed a robust reconstitution of human erythropoiesis and thrombopoiesis with terminal maturation in the bone marrow. Furthermore, depletion of host macrophages by clodronate administration resulted in the presence of human erythrocytes and platelets in the circulation. Thus, attenuation of mouse KIT signaling greatly enhances the multi-lineage differentiation of human hematopoietic stem and progenitor cells (HSPCs in mouse bone marrow, presumably by outcompeting mouse HSPCs to occupy suitable microenvironments. The BRGSKWv/Wv mouse model is a useful tool to study human multi-lineage hematopoiesis.

  11. Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2017-03-01

    Full Text Available The truncated mutant form of the charged multivesicular body protein 2B (CHMP2B is causative for frontotemporal dementia linked to chromosome 3 (FTD3. CHMP2B is a constituent of the endosomal sorting complex required for transport (ESCRT and, when mutated, disrupts endosome-to-lysosome trafficking and substrate degradation. To understand the underlying molecular pathology, FTD3 patient induced pluripotent stem cells (iPSCs were differentiated into forebrain-type cortical neurons. FTD3 neurons exhibited abnormal endosomes, as previously shown in patients. Moreover, mitochondria of FTD3 neurons displayed defective cristae formation, accompanied by deficiencies in mitochondrial respiration and increased levels of reactive oxygen. In addition, we provide evidence for perturbed iron homeostasis, presenting an in vitro patient-specific model to study the effects of iron accumulation in neurodegenerative diseases. All phenotypes observed in FTD3 neurons were rescued in CRISPR/Cas9-edited isogenic controls. These findings illustrate the relevance of our patient-specific in vitro models and open up possibilities for drug target development.

  12. A nonlinear delayed model for the immune response in the presence of viral mutation

    Science.gov (United States)

    Messias, D.; Gleria, Iram; Albuquerque, S. S.; Canabarro, Askery; Stanley, H. E.

    2018-02-01

    We consider a delayed nonlinear model of the dynamics of the immune system against a viral infection that contains a wild-type virus and a mutant. We consider the finite response time of the immune system and find sustained oscillatory behavior as well as chaotic behavior triggered by the presence of delays. We present a numeric analysis and some analytical results.

  13. Ultra-precision bearings

    CERN Document Server

    Wardle, F

    2015-01-01

    Ultra-precision bearings can achieve extreme accuracy of rotation, making them ideal for use in numerous applications across a variety of fields, including hard disk drives, roundness measuring machines and optical scanners. Ultraprecision Bearings provides a detailed review of the different types of bearing and their properties, as well as an analysis of the factors that influence motion error, stiffness and damping. Following an introduction to basic principles of motion error, each chapter of the book is then devoted to the basic principles and properties of a specific type of bearin

  14. Knock-in of a FLT3/ITD mutation cooperates with a NUP98-HOXD13 fusion to generate acute myeloid leukemia in a mouse model.

    Science.gov (United States)

    Greenblatt, Sarah; Li, Li; Slape, Christopher; Nguyen, Bao; Novak, Rachel; Duffield, Amy; Huso, David; Desiderio, Stephen; Borowitz, Michael J; Aplan, Peter; Small, Donald

    2012-03-22

    Constitutive activation of FLT3 by internal tandem duplication (ITD) is one of the most common molecular alterations in acute myeloid leukemia (AML). FLT3/ITD mutations have also been observed in myelodysplastic syndrome patients both before and during progression to AML. Previous work has shown that insertion of an FLT3/ITD mutation into the murine Flt3 gene induces a myeloproliferative neoplasm, but not progression to acute leukemia, suggesting that additional cooperating events are required. We therefore combined the FLT3/ITD mutation with a model of myelodysplastic syndrome involving transgenic expression of the Nup98-HoxD13 (NHD13) fusion gene. Mice expressing both the FLT3/ITD and NHD13 transgene developed AML with 100% penetrance and short latency. These leukemias were driven by mutant FLT3 expression and were susceptible to treatment with FLT3 tyrosine kinase inhibitors. We also observed a spontaneous loss of the wild-type Flt3 allele in these AMLs, further modeling the loss of the heterozygosity phenomenon that is seen in human AML with FLT3-activating mutations. Because resistance to FLT3 inhibitors remains an important clinical issue, this model may help identify new molecular targets in collaborative signaling pathways.

  15. Genomic evidence for island population conversion resolves conflicting theories of polar bear evolution.

    Directory of Open Access Journals (Sweden)

    James A Cahill

    Full Text Available Despite extensive genetic analysis, the evolutionary relationship between polar bears (Ursus maritimus and brown bears (U. arctos remains unclear. The two most recent comprehensive reports indicate a recent divergence with little subsequent admixture or a much more ancient divergence followed by extensive admixture. At the center of this controversy are the Alaskan ABC Islands brown bears that show evidence of shared ancestry with polar bears. We present an analysis of genome-wide sequence data for seven polar bears, one ABC Islands brown bear, one mainland Alaskan brown bear, and a black bear (U. americanus, plus recently published datasets from other bears. Surprisingly, we find clear evidence for gene flow from polar bears into ABC Islands brown bears but no evidence of gene flow from brown bears into polar bears. Importantly, while polar bears contributed <1% of the autosomal genome of the ABC Islands brown bear, they contributed 6.5% of the X chromosome. The magnitude of sex-biased polar bear ancestry and the clear direction of gene flow suggest a model wherein the enigmatic ABC Island brown bears are the descendants of a polar bear population that was gradually converted into brown bears via male-dominated brown bear admixture. We present a model that reconciles heretofore conflicting genetic observations. We posit that the enigmatic ABC Islands brown bears derive from a population of polar bears likely stranded by the receding ice at the end of the last glacial period. Since then, male brown bear migration onto the island has gradually converted these bears into an admixed population whose phenotype and genotype are principally brown bear, except at mtDNA and X-linked loci. This process of genome erosion and conversion may be a common outcome when climate change or other forces cause a population to become isolated and then overrun by species with which it can hybridize.

  16. Genomic evidence for island population conversion resolves conflicting theories of polar bear evolution.

    Science.gov (United States)

    Cahill, James A; Green, Richard E; Fulton, Tara L; Stiller, Mathias; Jay, Flora; Ovsyanikov, Nikita; Salamzade, Rauf; St John, John; Stirling, Ian; Slatkin, Montgomery; Shapiro, Beth

    2013-01-01

    Despite extensive genetic analysis, the evolutionary relationship between polar bears (Ursus maritimus) and brown bears (U. arctos) remains unclear. The two most recent comprehensive reports indicate a recent divergence with little subsequent admixture or a much more ancient divergence followed by extensive admixture. At the center of this controversy are the Alaskan ABC Islands brown bears that show evidence of shared ancestry with polar bears. We present an analysis of genome-wide sequence data for seven polar bears, one ABC Islands brown bear, one mainland Alaskan brown bear, and a black bear (U. americanus), plus recently published datasets from other bears. Surprisingly, we find clear evidence for gene flow from polar bears into ABC Islands brown bears but no evidence of gene flow from brown bears into polar bears. Importantly, while polar bears contributed bear, they contributed 6.5% of the X chromosome. The magnitude of sex-biased polar bear ancestry and the clear direction of gene flow suggest a model wherein the enigmatic ABC Island brown bears are the descendants of a polar bear population that was gradually converted into brown bears via male-dominated brown bear admixture. We present a model that reconciles heretofore conflicting genetic observations. We posit that the enigmatic ABC Islands brown bears derive from a population of polar bears likely stranded by the receding ice at the end of the last glacial period. Since then, male brown bear migration onto the island has gradually converted these bears into an admixed population whose phenotype and genotype are principally brown bear, except at mtDNA and X-linked loci. This process of genome erosion and conversion may be a common outcome when climate change or other forces cause a population to become isolated and then overrun by species with which it can hybridize.

  17. Analysis of thermoelastohydrodynamic performance of journal misaligned engine main bearings

    Science.gov (United States)

    Bi, Fengrong; Shao, Kang; Liu, Changwen; Wang, Xia; Zhang, Jian

    2015-05-01

    To understand the engine main bearings' working condition is important in order to improve the performance of engine. However, thermal effects and thermal effect deformations of engine main bearings are rarely considered simultaneously in most studies. A typical finite element model is selected and the effect of thermoelastohydrodynamic(TEHD) reaction on engine main bearings is investigated. The calculated method of main bearing's thermal hydrodynamic reaction and journal misalignment effect is finite difference method, and its deformation reaction is calculated by using finite element method. The oil film pressure is solved numerically with Reynolds boundary conditions when various bearing characteristics are calculated. The whole model considers a temperature-pressure-viscosity relationship for the lubricant, surface roughness effect, and also an angular misalignment between the journal and the bearing. Numerical simulations of operation of a typical I6 diesel engine main bearing is conducted and importance of several contributing factors in mixed lubrication is discussed. The performance characteristics of journal misaligned main bearings under elastohydrodynamic(EHD) and TEHD loads of an I6 diesel engine are received, and then the journal center orbit movement, minimum oil film thickness and maximum oil film pressure of main bearings are estimated over a wide range of engine operation. The model is verified through the comparison with other present models. The TEHD performance of engine main bearings with various effects under the influences of journal misalignment is revealed, this is helpful to understand EHD and TEHD effect of misaligned engine main bearings.

  18. Investigation of Bearing Technology

    National Research Council Canada - National Science Library

    Maciag, Walter

    1998-01-01

    .... They eliminate roller needles and balls in bearings. Since the GC design does not require lubrication maintenance, there is no need for the u-joint cross to contain lubrication reservoirs and distribution channels and their input fitting...

  19. DW_BEAR

    Data.gov (United States)

    Department of Homeland Security — Subset of BEAR (Bi-Weekly Examination Analysis and Reporting) data used for financial audit remediation reporting within the Coast Guard Business Intelligence (CGBI)...

  20. Gear bearing drive

    Science.gov (United States)

    Weinberg, Brian (Inventor); Mavroidis, Constantinos (Inventor); Vranish, John M. (Inventor)

    2011-01-01

    A gear bearing drive provides a compact mechanism that operates as an actuator providing torque and as a joint providing support. The drive includes a gear arrangement integrating an external rotor DC motor within a sun gear. Locking surfaces maintain the components of the drive in alignment and provide support for axial loads and moments. The gear bearing drive has a variety of applications, including as a joint in robotic arms and prosthetic limbs.

  1. Rolling bearing analysis

    CERN Document Server

    Harris, Tedric A

    2001-01-01

    One of the most well-known experts in the field brings cutting-edge research to practitioners in the new edition of this important reference. Covers the improved mathematical calculations for rolling bearing endurance developed by the American Society of Mechanical Engineers and the Society of Lubrication and Tribology Engineers. Updated with new material on Condition-Based Maintenance, new testing methods, and new bearing materials.

  2. Load responsive hydrodynamic bearing

    Science.gov (United States)

    Kalsi, Manmohan S.; Somogyi, Dezso; Dietle, Lannie L.

    2002-01-01

    A load responsive hydrodynamic bearing is provided in the form of a thrust bearing or journal bearing for supporting, guiding and lubricating a relatively rotatable member to minimize wear thereof responsive to relative rotation under severe load. In the space between spaced relatively rotatable members and in the presence of a liquid or grease lubricant, one or more continuous ring shaped integral generally circular bearing bodies each define at least one dynamic surface and a plurality of support regions. Each of the support regions defines a static surface which is oriented in generally opposed relation with the dynamic surface for contact with one of the relatively rotatable members. A plurality of flexing regions are defined by the generally circular body of the bearing and are integral with and located between adjacent support regions. Each of the flexing regions has a first beam-like element being connected by an integral flexible hinge with one of the support regions and a second beam-like element having an integral flexible hinge connection with an adjacent support region. A least one local weakening geometry of the flexing region is located intermediate the first and second beam-like elements. In response to application of load from one of the relatively rotatable elements to the bearing, the beam-like elements and the local weakening geometry become flexed, causing the dynamic surface to deform and establish a hydrodynamic geometry for wedging lubricant into the dynamic interface.

  3. Autosomal dominant hypercalciuria in a mouse model due to a mutation of the epithelial calcium channel, TRPV5.

    Directory of Open Access Journals (Sweden)

    Nellie Y Loh

    Full Text Available Hypercalciuria is a major cause of nephrolithiasis, and is a common and complex disorder involving genetic and environmental factors. Identification of genetic factors for monogenic forms of hypercalciuria is hampered by the limited availability of large families, and to facilitate such studies, we screened for hypercalciuria in mice from an N-ethyl-N-nitrosourea mutagenesis programme. We identified a mouse with autosomal dominant hypercalciuria (HCALC1. Linkage studies mapped the Hcalc1 locus to a 11.94 Mb region on chromosome 6 containing the transient receptor potential cation channel, subfamily V, members 5 (Trpv5 and 6 (Trpv6 genes. DNA sequence analysis of coding regions, intron-exon boundaries and promoters of Trpv5 and Trpv6 identified a novel T to C transition in codon 682 of TRPV5, mutating a conserved serine to a proline (S682P. Compared to wild-type littermates, heterozygous (Trpv5(682P/+ and homozygous (Trpv5(682P/682P mutant mice had hypercalciuria, polyuria, hyperphosphaturia and a more acidic urine, and ∼10% of males developed tubulointerstitial nephritis. Trpv5(682P/682P mice also had normal plasma parathyroid hormone but increased 1,25-dihydroxyvitamin D(3 concentrations without increased bone resorption, consistent with a renal defect for the hypercalciuria. Expression of the S682P mutation in human embryonic kidney cells revealed that TRPV5-S682P-expressing cells had a lower baseline intracellular calcium concentration than wild-type TRPV5-expressing cells, suggesting an altered calcium permeability. Immunohistological studies revealed a selective decrease in TRPV5-expression from the renal distal convoluted tubules of Trpv5(682P/+ and Trpv5(682P/682P mice consistent with a trafficking defect. In addition, Trpv5(682P/682P mice had a reduction in renal expression of the intracellular calcium-binding protein, calbindin-D(28K, consistent with a specific defect in TRPV5-mediated renal calcium reabsorption. Thus, our findings

  4. Is Polar Bear Hair Fiber Optic?

    Science.gov (United States)

    Koon, Daniel W.

    1998-05-01

    New direct measurement of high optical attenuation rates in polar bear hairs 2 8 dB mm in the visible and reanalysis of the data of Tributsch et al . Sol. Energy Mater. 21, 219 (1990) seem to rule out the UV waveguiding proposed by Grojean et al . Appl. Opt. 19, 339 (1980) . The case against fiber-optic polar bear hairs is summarized, and four conditions are given that any variation of the model of Grojean et al . would have to satisfy.

  5. Investigation Of Tribologic Processes in Bearing Nodes with the Use of the Fam-C And Fdm-A Methods – The Model With Elevated Passive Resistance

    Directory of Open Access Journals (Sweden)

    Gębura Andrzej

    2014-12-01

    Full Text Available The paper discloses selected results of application of the FAM-C (a.c. generator and FDM-A (d.c. generator methods for comprehensive troubleshooting of bearing nodes in single-spool turbojet engines.

  6. Polar bears and sea ice habitat change

    Science.gov (United States)

    Durner, George M.; Atwood, Todd C.; Butterworth, Andy

    2017-01-01

    The polar bear (Ursus maritimus) is an obligate apex predator of Arctic sea ice and as such can be affected by climate warming-induced changes in the extent and composition of pack ice and its impacts on their seal prey. Sea ice declines have negatively impacted some polar bear subpopulations through reduced energy input because of loss of hunting habitats, higher energy costs due to greater ice drift, ice fracturing and open water, and ultimately greater challenges to recruit young. Projections made from the output of global climate models suggest that polar bears in peripheral Arctic and sub-Arctic seas will be reduced in numbers or become extirpated by the end of the twenty-first century if the rate of climate warming continues on its present trajectory. The same projections also suggest that polar bears may persist in the high-latitude Arctic where heavy multiyear sea ice that has been typical in that region is being replaced by thinner annual ice. Underlying physical and biological oceanography provides clues as to why polar bear in some regions are negatively impacted, while bears in other regions have shown no apparent changes. However, continued declines in sea ice will eventually challenge the survival of polar bears and efforts to conserve them in all regions of the Arctic.

  7. Selected mice models based on APP, MAPT and presenilin gene mutations in research on the pathogenesis of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Magdalena Więdłocha

    2012-06-01

    Full Text Available  The research conducted on animal models of Alzheimer’s disease (AD has provided valuable information about the pathogenesis of this disease and associated behavioral and cognitive deficits as well as the disease-associated anatomical and histopathological lesions of the brain. Transgenic technologies have enabled the creation of animal models based on mutations in APP, MAPT, presenilin genes, tau protein and apoE. Due to economic reasons studies are mainly conducted on mice. Their brain tissue, depending on the mutation, is characterized by histopathological changes, such as the presence of amyloid plaques, tau protein deposits and dystrophic neurites, gliosis, hippocampal atrophy and amyloid accumulation in vessels. Animal cognitive impairment and behavior, which can be demonstrated in behavioral tests, primarily relate to the working and reference memory, alternation and anxiety. Unfortunately, despite the various modifications specific to AD in the genome of animals, scientists have failed to create an animal model characterized by all the pathological changes that can occur in Alzheimer’s disease. Nevertheless, the role of transgenic animals is undeniable, both in research on AD neuropathology and for testing new therapies, such as immunotherapy. Despite the occurrence of abundant Alzheimer’s disease mice models this article is dedicated to selected models with mutations in the APP, MAPT and presenilin genes and their application for behavioral studies.

  8. Repurposing Pan-HDAC Inhibitors for ARID1A-Mutated Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Takeshi Fukumoto

    2018-03-01

    Full Text Available Summary: ARID1A, a subunit of the SWI/SNF complex, is among the most frequently mutated genes across cancer types. ARID1A is mutated in more than 50% of ovarian clear cell carcinomas (OCCCs, diseases that have no effective therapy. Here, we show that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in ovarian cancers. This correlated with enhanced growth suppression induced by the inhibition of HDAC2 activity in ARID1A-mutated cells. HDAC2 interacts with EZH2 in an ARID1A status-dependent manner. HDAC2 functions as a co-repressor of EZH2 to suppress the expression of EZH2/ARID1A target tumor suppressor genes such as PIK3IP1 to inhibit proliferation and promote apoptosis. SAHA reduced the growth and ascites of the ARID1A-inactivated OCCCs in both orthotopic and genetic mouse models. This correlated with a significant improvement of survival of mice bearing ARID1A-mutated OCCCs. These findings provided preclinical rationales for repurposing FDA-approved pan-HDAC inhibitors for treating ARID1A-mutated cancers. : Fukumoto et al. show that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in ovarian cancers. This correlated with enhanced growth suppression induced by the inhibition of HDAC2 activity in ARID1A-mutated cells. These findings provided preclinical rationales for repurposing FDA-approved pan-HDAC inhibitors for treating ARID1A-mutated cancers. Keywords: ovarian cancer, ARID1A, HDAC2, pan-HDAC inhibitor, SAHA, SWI/SNF, chromatin remodeling

  9. An "ex vivo model" contributing to the diagnosis and evaluation of new drugs in cystic fibrosis.

    Science.gov (United States)

    Di Lullo, A M; Scorza, M; Amato, F; Comegna, M; Raia, V; Maiuri, L; Ilardi, G; Cantone, E; Castaldo, G; Iengo, M

    2017-06-01

    Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. About 2000 mutations have been described so far. We setup an ex vivo model of human nasal epithelial cells (HNECs) to study CF patients testing the effect of novel mutations and molecular therapies. We performed sampling (by brushing), followed by culture and analysis of HNECs using a series of molecular techniques. We performed 50 brushings from CF patients and controls. Using cultured cells, we: i) demonstrated the widely heterogeneous CFTR expression in patients and in controls; ii) defined the splicing effect of a CFTR mutation; iii) assessed the CFTR gating activity in patients bearing different mutations; iv) demonstrated that butyrate significantly enhances CFTR expression. Based on our data, we can conclude: 1) HNEC brushing is performed without anaesthesia and is well tolerated in all CF patients (children and adults); 2) HNECs can be preserved for up to 48 hours before culture allowings multicentre studies; 3) HNECs culture can be considered a suitable model to study the molecular effects of new CFTR gene mutations and/or uncertain meaning specific mutations of carriers; 4) an ex vivo model of HNECs may be used to evaluate, before human use, the effect of new drugs on patients' cells bearing specific CFTR mutations; 5) the methodology is adequate for a quantitative measurement, by fluorescence, of the CFTR gating activity of the HNECs from patients with different genotypes identifying: a) CF patients bearing two severe mutations with an activity < 10% (compared to controls - 100%); b) CF patients bearing at least a mild mutation with an activity of 10-20%; c) CF carriers (heterozygous subjects) with an activity between 40-70%. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.

  10. Glycerol hypersensitivity in a Drosophila model for glycerol kinase deficiency is affected by mutations in eye pigmentation genes.

    Directory of Open Access Journals (Sweden)

    Patrick J Wightman

    Full Text Available Glycerol kinase plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP dependent reaction. In humans, glycerol kinase deficiency results in a wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. In an effort to help understand the pathogenic mechanisms underlying the phenotypic variation, we have created a Drosophila model for glycerol kinase deficiency by RNAi targeting of dGyk (CG18374 and dGK (CG7995. As expected, RNAi flies have reduced glycerol kinase RNA expression, reduced phosphorylation activity and elevated glycerol levels. Further investigation revealed these flies to be hypersensitive to fly food supplemented with glycerol. Due to the hygroscopic nature of glycerol, we predict glycerol hypersensitivity is a result of greater susceptibility to desiccation, suggesting glycerol kinase to play an important role in desiccation resistance in insects. To evaluate a role for genetic modifier loci in determining severity of the glycerol hypersensitivity observed in knockdown flies, we performed a preliminary screen of lethal transposon insertion mutant flies using a glycerol hypersensitive survivorship assay. We demonstrate that this type of screen can identify both enhancer and suppressor genetic loci of glycerol hypersensitivity. Furthermore, we found that the glycerol hypersensitivity phenotype can be enhanced or suppressed by null mutations in eye pigmentation genes. Taken together, our data suggest proteins encoded by eye pigmentation genes play an important role in desiccation resistance and that eye pigmentation genes are strong modifiers of the glycerol hypersensitive phenotype identified in our Drosophila model for glycerol kinase deficiency.

  11. Evidence for a dualistic model of high-grade serous carcinoma: BRCA mutation status, histology, and tubal intraepithelial carcinoma.

    Science.gov (United States)

    Howitt, Brooke E; Hanamornroongruang, Suchanan; Lin, Douglas I; Conner, James E; Schulte, Stephanie; Horowitz, Neil; Crum, Christopher P; Meserve, Emily E

    2015-03-01

    Most early adnexal carcinomas detected in asymptomatic women with germline BRCA mutations (BRCA) present as serous tubal intraepithelial carcinomas (STIC). However, STICs are found in only ∼40% of symptomatic high-grade serous carcinomas (HGSCs) and less frequently in pseudoendometrioid variants of HGSC. Consecutive cases of untreated HGSC from BRCA and BRCA women with detailed fallopian tube examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined, and tumors were classified morphologically as SET ("SET", >50% solid, pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET tumors trended toward a higher frequency in BRCA versus BRCA women (50% vs. 28%, P=0.11), had a significantly younger mean age than those with classic HGSC in BRCA women (mean 56.2 vs. 64.8 y, P=0.04), and displayed a better clinical outcome in both groups combined (P=0.024). STIC was significantly more frequent in tumors from the BRCA cohort (66% vs. 31%, P=0.017) and specifically the BRCA tumors with classic morphology (83%) versus those with SET morphology (22%, P=0.003). Overall, several covariables-histology, BRCA status, age, coexisting STIC, and response to therapy-define 2 categories of HGSC with differences in precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic HGSC model that could shed light on the differences in frequency of STIC between symptomatic and asymptomatic women with HGSC. This model emphasizes the need for further study of HGSC precursors to determine their relevance to the prevention of this lethal malignancy.

  12. Glycerol Hypersensitivity in a Drosophila Model for Glycerol Kinase Deficiency Is Affected by Mutations in Eye Pigmentation Genes

    Science.gov (United States)

    Wightman, Patrick J.; Jackson, George R.; Dipple, Katrina M.

    2012-01-01

    Glycerol kinase plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP dependent reaction. In humans, glycerol kinase deficiency results in a wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. In an effort to help understand the pathogenic mechanisms underlying the phenotypic variation, we have created a Drosophila model for glycerol kinase deficiency by RNAi targeting of dGyk (CG18374) and dGK (CG7995). As expected, RNAi flies have reduced glycerol kinase RNA expression, reduced phosphorylation activity and elevated glycerol levels. Further investigation revealed these flies to be hypersensitive to fly food supplemented with glycerol. Due to the hygroscopic nature of glycerol, we predict glycerol hypersensitivity is a result of greater susceptibility to desiccation, suggesting glycerol kinase to play an important role in desiccation resistance in insects. To evaluate a role for genetic modifier loci in determining severity of the glycerol hypersensitivity observed in knockdown flies, we performed a preliminary screen of lethal transposon insertion mutant flies using a glycerol hypersensitive survivorship assay. We demonstrate that this type of screen can identify both enhancer and suppressor genetic loci of glycerol hypersensitivity. Furthermore, we found that the glycerol hypersensitivity phenotype can be enhanced or suppressed by null mutations in eye pigmentation genes. Taken together, our data suggest proteins encoded by eye pigmentation genes play an important role in desiccation resistance and that eye pigmentation genes are strong modifiers of the glycerol hypersensitive phenotype identified in our Drosophila model for glycerol kinase deficiency. PMID:22427807

  13. Watchable Wildlife: The Black Bear

    Science.gov (United States)

    Lynn L. Rogers

    1992-01-01

    Black bears are the bears people most often encounter. Black bears live in forests over much of North America, unlike grizzlies that live only in Alaska, northern and western Canada, and the northern Rocky Mountains. This brochure presents the latest information on black bear life and how this species responds to an ever-increasing number of campers, hikers, and...

  14. Climate Drives Polar Bear Origins

    Science.gov (United States)

    In their provocative analysis of northern bears (“Nuclear genomic sequences reveal that polar bears are an old and distinct bear lineage,” Reports, 20 April, p. 344), F. Hailer et al. use independent nuclear loci to show that polar bears originated during the middle Pleistocene, rather than during t...

  15. Morphological comparison of the craniofacial phenotypes of mouse models expressing the Apert FGFR2 S252W mutation in neural crest- or mesoderm-derived tissues.

    Science.gov (United States)

    Heuzé, Yann; Singh, Nandini; Basilico, Claudio; Jabs, Ethylin Wang; Holmes, Greg; Richtsmeier, Joan T

    2014-06-01

    Bones of the craniofacial skeleton are derived from two distinct cell lineages, cranial neural crest and mesoderm, and articulate at sutures and synchondroses which represent major bone growth sites. Premature fusion of cranial suture(s) is associated with craniofacial dysmorphogenesis caused in part by alteration in the growth potential at sutures and can occur as an isolated birth defect or as part of a syndrome, such as Apert syndrome. Conditional expression of the Apert FGFR2 S252W mutation in cells derived from mesoderm was previously shown to be necessary and sufficient to cause coronal craniosynostosis. Here we used micro computed tomography images of mice expressing the Apert mutation constitutively in either mesoderm- or neural crest-derived cells to quantify craniofacial shape variation and suture fusion patterns, and to identify shape changes in craniofacial bones derived from the lineage not expressing the mutation, referred to here as secondary shape changes. Our results show that at postnatal day 0: (i) conditional expression of the FGFR2 S252W mutation in neural crest-derived tissues causes a more severe craniofacial phenotype than when expressed in mesoderm-derived tissues; and (ii) both mesoderm- and neural crest-specific mouse models display secondary shape changes. We also show that premature suture fusion is not necessarily dependent on the expression of the FGFR2 S252W mutation in the sutural mesenchyme. More specifically, it appears that suture fusion patterns in both mouse models are suture-specific resulting from a complex combination of the influence of primary abnormalities of biogenesis or signaling within the sutures, and timing. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Structural insight with mutational impact on tyrosinase and PKC-β interaction from Homo sapiens: Molecular modeling and docking studies for melanogenesis, albinism and increased risk for melanoma.

    Science.gov (United States)

    Banerjee, Arundhati; Ray, Sujay

    2016-10-30

    Human tyrosinase, is an important protein for biosynthetic pathway of melanin. It was studied to be phosphorylated and activated by protein kinase-C, β-subunit (PKC-β) through earlier experimentations with in vivo evidences. Documentation documents that mutation in two essentially vital serine residues in C-terminal end of tyrosinase leads to albinism. Due to the deficiency of protective shield like enzyme; melanin, albinos are at an increased peril for melanoma and other skin cancers. So, computational and residue-level insight including a mutational exploration with evolutionary importance into this mechanism lies obligatory for future pathological and therapeutic developments. Therefore, functional tertiary models of the relevant proteins were analyzed after satisfying their stereo-chemical features. Evolutionarily paramount residues for the activation of tyrosinase were perceived via multiple sequence alignment phenomena. Mutant-type tyrosinase protein (S98A and S102A) was thereby modeled, maintaining the wild-type proteins' functionality. Furthermore, this present comparative study discloses the variation in the stable residual participation (for mutant-type and wild-type tyrosinase-PKCβ complex). Mainly, an increased number of polar negatively charged residues from the wild-type tyrosinase participated with PKC-β, predominantly. Fascinatingly supported by evaluation of statistical significances, mutation even led to a destabilizing impact in tyrosinase accompanied by conformational switches with a helix-to-coil transition in the mutated protein. Even the allosteric sites in the protein got poorly hampered upon mutation leading to weaker tendency for binding partners to interact. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Rotordynamic and friction loss measurements on a high speed Laval rotor supported by floating ring bearings

    NARCIS (Netherlands)

    Eling, R.P.T.; te Wierik, M.; van Ostayen, R.A.J.; Rixen, DJ

    2017-01-01

    Floating ring bearings are the commonly used type of bearing for automotive turbochargers. The automotive industry continuously investigates how to reduce the bearing friction losses and how to create silent turbochargers. Many of these studies involve creating a numerical model of the rotor-bearing

  18. Spatial Distribution of Black Bear Incident Reports in Michigan.

    Directory of Open Access Journals (Sweden)

    Jamie E McFadden-Hiller

    Full Text Available Interactions between humans and carnivores have existed for centuries due to competition for food and space. American black bears are increasing in abundance and populations are expanding geographically in many portions of its range, including areas that are also increasing in human density, often resulting in associated increases in human-bear conflict (hereafter, bear incidents. We used public reports of bear incidents in Michigan, USA, from 2003-2011 to assess the relative contributions of ecological and anthropogenic variables in explaining the spatial distribution of bear incidents and estimated the potential risk of bear incidents. We used weighted Normalized Difference Vegetation Index mean as an index of primary productivity, region (i.e., Upper Peninsula or Lower Peninsula, primary and secondary road densities, and percentage land cover type within 6.5-km2 circular buffers around bear incidents and random points. We developed 22 a priori models and used generalized linear models and Akaike's Information Criterion (AIC to rank models. The global model was the best compromise between model complexity and model fit (w = 0.99, with a ΔAIC 8.99 units from the second best performing model. We found that as deciduous forest cover increased, the probability of bear incident occurrence increased. Among the measured anthropogenic variables, cultivated crops and primary roads were the most important in our AIC-best model and were both positively related to the probability of bear incident occurrence. The spatial distribution of relative bear incident risk varied markedly throughout Michigan. Forest cover fragmented with agriculture and other anthropogenic activities presents an environment that likely facilitates bear incidents. Our map can help wildlife managers identify areas of bear incident occurrence, which in turn can be used to help develop strategies aimed at reducing incidents. Researchers and wildlife managers can use similar mapping

  19. Spatial Distribution of Black Bear Incident Reports in Michigan.

    Science.gov (United States)

    McFadden-Hiller, Jamie E; Beyer, Dean E; Belant, Jerrold L

    2016-01-01

    Interactions between humans and carnivores have existed for centuries due to competition for food and space. American black bears are increasing in abundance and populations are expanding geographically in many portions of its range, including areas that are also increasing in human density, often resulting in associated increases in human-bear conflict (hereafter, bear incidents). We used public reports of bear incidents in Michigan, USA, from 2003-2011 to assess the relative contributions of ecological and anthropogenic variables in explaining the spatial distribution of bear incidents and estimated the potential risk of bear incidents. We used weighted Normalized Difference Vegetation Index mean as an index of primary productivity, region (i.e., Upper Peninsula or Lower Peninsula), primary and secondary road densities, and percentage land cover type within 6.5-km2 circular buffers around bear incidents and random points. We developed 22 a priori models and used generalized linear models and Akaike's Information Criterion (AIC) to rank models. The global model was the best compromise between model complexity and model fit (w = 0.99), with a ΔAIC 8.99 units from the second best performing model. We found that as deciduous forest cover increased, the probability of bear incident occurrence increased. Among the measured anthropogenic variables, cultivated crops and primary roads were the most important in our AIC-best model and were both positively related to the probability of bear incident occurrence. The spatial distribution of relative bear incident risk varied markedly throughout Michigan. Forest cover fragmented with agriculture and other anthropogenic activities presents an environment that likely facilitates bear incidents. Our map can help wildlife managers identify areas of bear incident occurrence, which in turn can be used to help develop strategies aimed at reducing incidents. Researchers and wildlife managers can use similar mapping techniques to

  20. Radial Halbach Magnetic Bearings

    Science.gov (United States)

    Eichenberg, Dennis J.; Gallo, Christopher A.; Thompson, William K.

    2009-01-01

    Radial Halbach magnetic bearings have been investigated as part of an effort to develop increasingly reliable noncontact bearings for future high-speed rotary machines that may be used in such applications as aircraft, industrial, and land-vehicle power systems and in some medical and scientific instrumentation systems. Radial Halbach magnetic bearings are based on the same principle as that of axial Halbach magnetic bearings, differing in geometry as the names of these two types of bearings suggest. Both radial and axial Halbach magnetic bearings are passive in the sense that unlike most other magnetic bearings that have been developed in recent years, they effect stable magnetic levitation without need for complex active control. Axial Halbach magnetic bearings were described in Axial Halbach Magnetic Bearings (LEW-18066-1), NASA Tech Briefs, Vol. 32, No. 7 (July 2008), page 85. In the remainder of this article, the description of the principle of operation from the cited prior article is recapitulated and updated to incorporate the present radial geometry. In simplest terms, the basic principle of levitation in an axial or radial Halbach magnetic bearing is that of the repulsive electromagnetic force between (1) a moving permanent magnet and (2) an electric current induced in a stationary electrical conductor by the motion of the magnetic field. An axial or radial Halbach bearing includes multiple permanent magnets arranged in a Halbach array ("Halbach array" is defined below) in a rotor and multiple conductors in the form of wire coils in a stator, all arranged so the rotary motion produces an axial or radial repulsion that is sufficient to levitate the rotor. A basic Halbach array (see Figure 1) consists of a row of permanent magnets, each oriented so that its magnetic field is at a right angle to that of the adjacent magnet, and the right-angle turns are sequenced so as to maximize the magnitude of the magnetic flux density on one side of the row while

  1. Cauli: a mouse strain with an Ift140 mutation that results in a skeletal ciliopathy modelling Jeune syndrome.

    Directory of Open Access Journals (Sweden)

    Kerry A Miller

    2013-08-01

    Full Text Available Cilia are architecturally complex organelles that protrude from the cell membrane and have signalling, sensory and motility functions that are central to normal tissue development and homeostasis. There are two broad categories of cilia; motile and non-motile, or primary, cilia. The central role of primary cilia in health and disease has become prominent in the past decade with the recognition of a number of human syndromes that result from defects in the formation or function of primary cilia. This rapidly growing class of conditions, now known as ciliopathies, impact the development of a diverse range of tissues including the neural axis, craniofacial structures, skeleton, kidneys, eyes and lungs. The broad impact of cilia dysfunction on development reflects the pivotal position of the primary cilia within a signalling nexus involving a growing number of growth factor systems including Hedgehog, Pdgf, Fgf, Hippo, Notch and both canonical Wnt and planar cell polarity. We have identified a novel ENU mutant allele of Ift140, which causes a mid-gestation embryonic lethal phenotype in homozygous mutant mice. Mutant embryos exhibit a range of phenotypes including exencephaly and spina bifida, craniofacial dysmorphism, digit anomalies, cardiac anomalies and somite patterning defects. A number of these phenotypes can be attributed to alterations in Hedgehog signalling, although additional signalling systems are also likely to be involved. We also report the identification of a homozygous recessive mutation in IFT140 in a Jeune syndrome patient. This ENU-induced Jeune syndrome model will be useful in delineating the origins of dysmorphology in human ciliopathies.

  2. A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.

    Directory of Open Access Journals (Sweden)

    Barbara Klink

    Full Text Available Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment.

  3. On the computation of electrical resistance of hydrodynamic journal bearing

    Directory of Open Access Journals (Sweden)

    Eleonora Pop

    2014-12-01

    Full Text Available The paper approaches the mathematical model of electrical resistance of hydrodynamic journal bearing under different parameters of operation so as to predict bearing performance and safe load carrying capacity. The currents circulating in the journal bearing of electrical machine causes reducing of lifespan by appearance of pitting on their surface and the degradation of the lubricant. In a hydrodynamic journal bearing, the zone of minimum film thickness, load-carrying oil film varies along the circumference of a bearing through its length. This has been found to form a capacitor of varying capacitance between the journal and the bearings dependent on permittivity of the lubricant used, the bearing length, the eccentricity ratio and the clearance ratio. Besides this, load-carrying on oil film offers resistance that depends on operating parameters and resistivity of the lubricant.

  4. Molecular modeling of sulfoxaflor and neonicotinoid binding in insect nicotinic acetylcholine receptors: impact of the Myzus β1 R81T mutation.

    Science.gov (United States)

    Wang, Nick X; Watson, Gerald B; Loso, Michael R; Sparks, Thomas C

    2016-08-01

    Sulfoxaflor (Isoclast™ active), a new sulfoximine-class insecticide, targets sap-feeding insect pests, including those resistant to neonicotinoids. Sulfoxaflor acts on the insect nicotinic acetylcholine receptor (nAChR) in a distinct manner relative to neonicotinoids. Unlike any of the neonicotinoids, sulfoxaflor has four stereoisomers. A homology model of Myzus persicae (green peach aphid) based on the ACh binding protein from Aplysia californica, overlaid with M. persicae nAChR sequence (α2 and β1 subunits) was used to investigate the interactions of the sulfoxaflor stereoisomers with WT and R81T versions of the nAChR. Whole-molecule van der Waals interactions are highly correlated with the binding affinity for the neonicotinoids and correctly predict the rank order of binding affinity for neonicotinoids and sulfoxaflor. The R81T mutation in M. persicae nAChR is predicted to have much less effect on binding of sulfoxaflor's stereoisomers than that of the neonicotinoids. All four stereoisomers predictably contribute to the activity of sulfoxaflor. The WT and R81T nAChR homology models suggest that changes in a whole-molecule electrostatic energy component can potentially explain the effects of this target-site mutation on the pattern of reduced efficacy for the modeled neonicotinoids, and provide a basis for the reduced effect of this mutation on sulfoxaflor. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  5. Research on bearing life prediction based on support vector machine and its application

    International Nuclear Information System (INIS)

    Sun Chuang; Zhang Zhousuo; He Zhengjia

    2011-01-01

    Life prediction of rolling element bearing is the urgent demand in engineering practice, and the effective life prediction technique is beneficial to predictive maintenance. Support vector machine (SVM) is a novel machine learning method based on statistical learning theory, and is of advantage in prediction. This paper develops SVM-based model for bearing life prediction. The inputs of the model are features of bearing vibration signal and the output is the bearing running time-bearing failure time ratio. The model is built base on a few failed bearing data, and it can fuse information of the predicted bearing. So it is of advantage to bearing life prediction in practice. The model is applied to life prediction of a bearing, and the result shows the proposed model is of high precision.

  6. Investigation of the local delivery of an intelligent chitosan-based 188Re thermosensitive in situ-forming hydrogel in an orthotopic hepatoma-bearing rat model

    International Nuclear Information System (INIS)

    Huang, Feng-Yun J.; Guo-Yi Gan; Ling-Kuen Huang; Jhen-Jie Hong; Bor-Tsung Hsieh; Wan-Yu Lin; Tsai-Yueh Luo

    2014-01-01

    In this study, in vitro and in vivo evaluations of the local delivery of 188 Re-Tin colloid and doxorubicin (Dox) through chitosan (C)-based thermosensitive in situ-forming hydrogels by intratumoral injection in an orthotopic hepatoma-bearing rat model were carried out. Selective internal radiation therapy has been increasingly used as an alternative therapy option for hepatocellular carcinoma (HCC) and combined with biodegradable drug carrier systems to improve drug delivery and systemic toxicity. The C-based thermosensitive hydrogel (C/GP), an injectable thermogelling solution crosslinked between C and β-glycerophosphate (GP), was induced as an implanted carrier to combine the 188 Re-Tin colloid and Dox as a novel treatment strategy. The compounded hydrogel characteristics, including the gelation time, controlled release of Dox, and morphology, were examined. In the animal study, the biodistribution, scintigraphy, therapeutic efficacy, and histopathology were also evaluated. The characterization results reveal that C/GP/Dox hydrogels have similar gelation times of 4-4.5 min and pore sizes of as small as 10 μm compared with C/GP hydrogels. The C/GP/Dox/ 188 Re-Tin colloids have the longest release time for Dox at 2-3 days. In the in vivo experiments, both the biodistribution and scintigraphy studies have the highest hydrogel uptakes in the tumor at different time points, as well as localized radioactivities for a certain time. The therapeutic evaluation indicates that C/GP/Dox/ 188 Re-Tin colloids can more significantly inhibit tumors compared with the control group at 2 and 4 weeks post-treatment. These results indicate that this novel treatment system is a promising option for inoperable HCC. (author)

  7. Pro-arrhythmogenic Effects of the V141M KCNQ1 Mutation in Short QT Syndrome and Its Potential Therapeutic Targets: Insights from Modeling.

    Science.gov (United States)

    Lee, Hsiang-Chun; Rudy, Yoram; Liang, Hongwu; Chen, Chih-Chieh; Luo, Ching-Hsing; Sheu, Sheng-Hsiung; Cui, Jianmin

    2017-10-01

    Gain-of-function mutations in the pore-forming subunit of I Ks channels, KCNQ1, lead to short QT syndrome (SQTS) and lethal arrhythmias. However, how mutant I Ks channels cause SQTS and the possibility of I Ks -specific pharmacological treatment remain unclear. V141M KCNQ1 is a SQTS associated mutation. We studied its effect on I Ks gating properties and changes in the action potentials (AP) of human ventricular myocytes. Xenopus oocytes were used to study the gating mechanisms of expressed V141M KCNQ1/KCNE1 channels. Computational models were used to simulate human APs in endocardial, mid-myocardial, and epicardial ventricular myocytes with and without β-adrenergic stimulation. V141M KCNQ1 caused a gain-of-function in I Ks characterized by increased current density, faster activation, and slower deactivation leading to I Ks accumulation. V141M KCNQ1 also caused a leftward shift of the conductance-voltage curve compared to wild type (WT) I Ks (V 1/2 = 33.6 ± 4.0 mV for WT, and 24.0 ± 1.3 mV for heterozygous V141M). A Markov model of heterozygous V141M mutant I Ks was developed and incorporated into the O'Hara-Rudy model. Compared to the WT, AP simulations demonstrated marked rate-dependent shortening of AP duration (APD) for V141M, predicting a SQTS phenotype. Transmural electrical heterogeneity was enhanced in heterozygous V141M AP simulations, especially under β-adrenergic stimulation. Computational simulations identified specific I K1 blockade as a beneficial pharmacologic target for reducing the transmural APD heterogeneity associated with V141M KCNQ1 mutation. V141M KCNQ1 mutation shortens ventricular APs and enhances transmural APD heterogeneity under β-adrenergic stimulation. Computational simulations identified I K1 blockers as a potential antiarrhythmic drug of choice for SQTS.

  8. Shaking table test of a base isolated model in main control room of nuclear power plant using LRB (lead rubber bearing)

    International Nuclear Information System (INIS)

    Ham, K. W.; Lee, K. J.; Suh, Y. P.

    2005-01-01

    LRB(Lead Rubber Bearing) is a widely used isolation system which is installed between equipment and foundation to reduce seismic vibration from ground. LRB is consist of bearings which are resistant to lateral motion and torsion and has a high vertical stiffness. For that reason, several studies are conducted to apply LRB to the nuclear power plant. In this study, we designed two types of main control floor systems (type I, type II) and a number of shaking table tests with and without isolation system were conducted to evaluate floor isolation effectiveness of LRB

  9. Hybrid superconductor magnet bearings

    Science.gov (United States)

    Chu, Wei-Kan

    1995-01-01

    Hybrid superconductor magnet bearings (HSMB's) utilize high temperature superconductors (HTS's) together with permanent magnets to form a frictionless interface between relatively rotating parts. They are low mass, stable, and do not incur expenditure of energy during normal operation. There is no direct physical contact between rotor and stator, and hence there is no wear and tear. However, just as any other applications of HTS's, it requires a very cold temperature to function. Whereas this might be perceived as a disadvantage on earth, it is of no great concern in space or on the moon. To astronomers, the moon is an excellent site for an observatory, but the cold and dusty vacuum environment on the moon precludes the use of mechanical bearings on the telescope mounts. Furthermore, drive mechanisms with very fine steps, and hence bearings with extremely low friction are needed to track a star from the moon, because the moon rotates very slowly. All aspects considered, the HSMB is about the only candidate that fits in naturally. Here, we present a design for one such bearing, capable of supporting a telescope that weighs about 3 lbs on Earth.

  10. Experimental Contribution to High Precision Characterization of Magnetic Forces in Active Magnetic Bearings

    DEFF Research Database (Denmark)

    Kjølhede, Klaus; Santos, Ilmar

    2006-01-01

    Parameter identification procedures and model validation are major steps towards intelligent machines supported by active magnetic bearings (AMB). The ability of measuring the electromagnetic bearing forces, or deriving them from measuring the magnetic flux, strongly contributes to the model vali...

  11. Adaptive mutation: has the unicorn landed?

    Science.gov (United States)

    Foster, P L

    1998-01-01

    Reversion of an episomal Lac- allele during lactose selection has been studied as a model for adaptive mutation. Although recent results show that the mutations that arise during selection are not "adaptive" in the original sense, the mutagenic mechanism that produces these mutations may nonetheless be of evolutionary significance. In addition, a transient mutational state induced in a subpopulation of starving cells could provide a species with a mechanism for adaptive evolution. PMID:9560365

  12. Design optimization and probabilistic analysis of a hydrodynamic journal bearing

    Science.gov (United States)

    Liniecki, Alexander G.

    1990-01-01

    A nonlinear constrained optimization of a hydrodynamic bearing was performed yielding three main variables: radial clearance, bearing length to diameter ratio, and lubricating oil viscosity. As an objective function a combined model of temperature rise and oil supply has been adopted. The optimized model of the bearing has been simulated for population of 1000 cases using Monte Carlo statistical method. It appeared that the so called 'optimal solution' generated more than 50 percent of failed bearings, because their minimum oil film thickness violated stipulated minimum constraint value. As a remedy change of oil viscosity is suggested after several sensitivities of variables have been investigated.

  13. Modeling the Mutational and Phenotypic Landscapes of Pelizaeus-Merzbacher Disease with Human iPSC-Derived Oligodendrocytes

    DEFF Research Database (Denmark)

    Nevin, Zachary S; Factor, Daniel C; Karl, Robert T

    2017-01-01

    testing of small-molecule modulators of the endoplasmic reticulum stress response, which improved both morphologic and myelination defects. Collectively, these data provide insights into the pathogeneses of a variety of PLP1 mutations and suggest that disparate etiologies of PMD could require specific...

  14. A mutate-and-map strategy accurately infers the base pairs of a 35-nucleotide model RNA

    Science.gov (United States)

    Kladwang, Wipapat; Cordero, Pablo; Das, Rhiju

    2011-01-01

    We present a rapid experimental strategy for inferring base pairs in structured RNAs via an information-rich extension of classic chemical mapping approaches. The mutate-and-map method, previously applied to a DNA/RNA helix, systematically searches for single mutations that enhance the chemical accessibility of base-pairing partners distant in sequence. To test this strategy for structured RNAs, we have carried out mutate-and-map measurements for a 35-nt hairpin, called the MedLoop RNA, embedded within an 80-nt sequence. We demonstrate the synthesis of all 105 single mutants of the MedLoop RNA sequence and present high-throughput DMS, CMCT, and SHAPE modification measurements for this library at single-nucleotide resolution. The resulting two-dimensional data reveal visually clear, punctate features corresponding to RNA base pair interactions as well as more complex features; these signals can be qualitatively rationalized by comparison to secondary structure predictions. Finally, we present an automated, sequence-blind analysis that permits the confident identification of nine of the 10 MedLoop RNA base pairs at single-nucleotide resolution, while discriminating against all 1460 false-positive base pairs. These results establish the accuracy and information content of the mutate-and-map strategy and support its feasibility for rapidly characterizing the base-pairing patterns of larger and more complex RNA systems. PMID:21239468

  15. Mutation in the AP4M1 Gene Provides a Model for Neuroaxonal Injury in Cerebral Palsy

    NARCIS (Netherlands)

    A.J.H.M. Verkerk (Annemieke); R. Schot (Rachel); B. Dumee (Belinda); K. Schellekens (Karlijn); S.M.A. Swagemakers (Sigrid); A.M. Bertoli Avella (Aida); M. Leguin (Maarten); J. Dudink (Jeroen); P. Govaert (Paul); A.L. van Zwol (Arjen); J. Hirst (Jennifer); M.W. Wessels (Marja); C.E. Catsman-Berrevoets (Coriene); F.W. Verheijen (Frans); E. de Graaff (Esther); I.F.M. de Coo (René); J.M. Kros (Johan); R. Willemsen (Rob); P.J. Willems (Patrick); P.J. van der Spek (Peter); G.M.S. Mancini (Grazia)

    2009-01-01

    textabstractCerebral palsy due to perinatal injury to cerebral white matter is usually not caused by genetic mutations, but by ischemia and/or inflammation. Here, we describe an autosomal-recessive type of tetraplegic cerebral palsy with mental retardation, reduction of cerebral white matter, and

  16. Primary hyperoxaluria type I: a model for multiple mutations in a monogenic disease within a distinct ethnic group

    NARCIS (Netherlands)

    Rinat, C.; Wanders, R. J.; Drukker, A.; Halle, D.; Frishberg, Y.

    1999-01-01

    Primary hyperoxaluria type 1 is an autosomal recessive inherited metabolic disease in which excessive oxalates are formed by the liver and excreted by the kidneys, causing a wide spectrum of phenotypes ranging from renal failure in infancy to mere renal stones in late adulthood. Mutations in the

  17. Substrate compositional variation with tissue/region and Gba1 mutations in mouse models--implications for Gaucher disease.

    Directory of Open Access Journals (Sweden)

    Ying Sun

    Full Text Available Gaucher disease results from GBA1 mutations that lead to defective acid β-glucosidase (GCase mediated cleavage of glucosylceramide (GC and glucosylsphingosine as well as heterogeneous manifestations in the viscera and CNS. The mutation, tissue, and age-dependent accumulations of different GC species were characterized in mice with Gba1 missense mutations alone or in combination with isolated saposin C deficiency (C*. Gba1 heteroallelism for D409V and null alleles (9V/null led to GC excesses primarily in the visceral tissues with preferential accumulations of lung GC24∶0, but not in liver, spleen, or brain. Age-dependent increases of different GC species were observed. The combined saposin C deficiency (C* with V394L homozygosity (4L;C* showed major GC18:0 degradation defects in the brain, whereas the analogous mice with D409H homozygosity and C* (9H;C* led to all GC species accumulating in visceral tissues. Glucosylsphingosine was poorly degraded in brain by V394L and D409H GCases and in visceral tissues by D409V GCase. The neonatal lethal N370S/N370S genotype had insignificant substrate accumulations in any tissue. These results demonstrate age, organ, and mutation-specific quantitative differences in GC species and glucosylsphingosine accumulations that can have influence in the tissue/regional expression of Gaucher disease phenotypes.

  18. Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation.

    Science.gov (United States)

    Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger

    2014-11-05

    Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

  19. A coarse-grained elastic network atom contact model and its use in the simulation of protein dynamics and the prediction of the effect of mutations.

    Directory of Open Access Journals (Sweden)

    Vincent Frappier

    2014-04-01

    Full Text Available Normal mode analysis (NMA methods are widely used to study dynamic aspects of protein structures. Two critical components of NMA methods are coarse-graining in the level of simplification used to represent protein structures and the choice of potential energy functional form. There is a trade-off between speed and accuracy in different choices. In one extreme one finds accurate but slow molecular-dynamics based methods with all-atom representations and detailed atom potentials. On the other extreme, fast elastic network model (ENM methods with Cα-only representations and simplified potentials that based on geometry alone, thus oblivious to protein sequence. Here we present ENCoM, an Elastic Network Contact Model that employs a potential energy function that includes a pairwise atom-type non-bonded interaction term and thus makes it possible to consider the effect of the specific nature of amino-acids on dynamics within the context of NMA. ENCoM is as fast as existing ENM methods and outperforms such methods in the generation of conformational ensembles. Here we introduce a new application for NMA methods with the use of ENCoM in the prediction of the effect of mutations on protein stability. While existing methods are based on machine learning or enthalpic considerations, the use of ENCoM, based on vibrational normal modes, is based on entropic considerations. This represents a novel area of application for NMA methods and a novel approach for the prediction of the effect of mutations. We compare ENCoM to a large number of methods in terms of accuracy and self-consistency. We show that the accuracy of ENCoM is comparable to that of the best existing methods. We show that existing methods are biased towards the prediction of destabilizing mutations and that ENCoM is less biased at predicting stabilizing mutations.

  20. The Effect of Non-Circular Bearing Shapes in Hydrodynamic Journal Bearings on the Vibration Behavior of Turbocharger Structures

    Directory of Open Access Journals (Sweden)

    Lukas Bernhauser

    2017-03-01

    Full Text Available Increasing quality demands of combustion engines require, amongst others, improvements of the engine’s acoustics and all (subcomponents mounted to the latter. A significant impact to the audible tonal noise spectrum results from the vibratory motions of fast-rotating turbocharger rotor systems in multiple hydrodynamic bearings such as floating bearing rings. Particularly, the study of self-excited non-linear vibrations of the rotor-bearing systems is crucial for the understanding, prevention or reduction of the noise and, consequently, for a sustainable engine acoustics development. This work presents an efficient modeling approach for the investigation, optimization, and design improvement of complex turbocharger rotors in hydrodynamic journal bearings, including floating bearing rings with circular and non-circular bearing geometries. The capability of tonal non-synchronous vibration prevention using non-circular bearing shapes is demonstrated with dynamic run-up simulations of the presented model. These findings and the performance of our model are compared and validated with results of a classical Laval/Jeffcott rotor-bearing model and a specific turbocharger model found in the literature. It is shown that the presented simulation method yields fast and accurate results and furthermore, that non-circular bearing shapes are an effective measure to reduce or even prevent self-excited tonal noise.

  1. A spontaneous Fatp4/Scl27a4 splice site mutation in a new murine model for congenital ichthyosis.

    Science.gov (United States)

    Tao, Jianning; Koster, Maranke I; Harrison, Wilbur; Moran, Jennifer L; Beier, David R; Roop, Dennis R; Overbeek, Paul A

    2012-01-01

    Congenital ichthyoses are life-threatening conditions in humans. We describe here the identification and molecular characterization of a novel recessive mutation in mice that results in newborn lethality with severe congenital lamellar ichthyosis. Mutant newborns have a taut, shiny, non-expandable epidermis that resembles cornified manifestations of autosomal-recessive congenital ichthyosis in humans. The skin is stretched so tightly that the newborn mice are immobilized. The genetic defect was mapped to a region near the proximal end of chromosome 2 by SNP analysis, suggesting Fatp4/Slc27a4 as a candidate gene. FATP4 mutations in humans cause ichthyosis prematurity syndrome (IPS), and mutations of Fatp4 in mice have previously been found to cause a phenotype that resembles human congenital ichthyoses. Characterization of the Fatp4 cDNA revealed a fusion of exon 8 to exon 10, with deletion of exon 9. Genomic sequencing identified an A to T mutation in the splice donor sequence at the 3'-end of exon 9. Loss of exon 9 results in a frame shift mutation upstream from the conserved very long-chain acyl-CoA synthase (VLACS) domain. Histological studies revealed that the mutant mice have defects in keratinocyte differentiation, along with hyperproliferation of the stratum basale of the epidermis, a hyperkeratotic stratum corneum, and reduced numbers of secondary hair follicles. Since Fatp4 protein is present primarily at the stratum granulosum and the stratum spinosum, the hyperproliferation and the alterations in hair follicle induction suggest that very long chain fatty acids, in addition to being required for normal cornification, may influence signals from the stratum corneum to the basal cells that help to orchestrate normal skin differentiation.

  2. Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma.

    Science.gov (United States)

    Pellegatta, Serena; Valletta, Lorella; Corbetta, Cristina; Patanè, Monica; Zucca, Ileana; Riccardi Sirtori, Federico; Bruzzone, Maria Grazia; Fogliatto, Gianpaolo; Isacchi, Antonella; Pollo, Bianca; Finocchiaro, Gaetano

    2015-01-21

    The R132H mutation of cytosolic isocitrate dehydrogenase (IDH1) is present in the majority of low grade gliomas.Immunotherapy in these tumors has an interesting, still unexploited, therapeutic potential, as they are less immunosuppressive than glioblastomas. Using site-directed mutagenesis we introduced the R132H mutation into the murine glioma cell line GL261,creating mIDH1-GL261. Presence of the mutation was confirmed by immunoblotting and production of the oncometabolite 2-hydroxyglutarate (2HG), demonstrated by mass spectrometry (LC-MS/MS) performed on cell supernatant. In vitro mIDH1-GL261 had different morphology but similar growth rate than parental GL261 (p-GL261). After intracranial injection, MRI suggested that the initial growth rate was slower in mIDH1-GL261 than p-GL261 gliomas but overall survival was similar. mIDH1-GL261 gliomas showed evidence of R132H expression and of intratumoral 2HG production (evaluated by MRS and LC-MS/MS). Immunizations were performed nine days after intracranial implantation of mIDH1- or p-GL261 cells by three subcutaneous injections of five different peptides encompassing the IDH1 mutation site, all emulsified with Montanide ISA-51, in association with GM-CSF. Control mice were injected with four ovalbumin peptides or vehicle. Mice with mIDH1-GL261 but not p-GL261 gliomas treated with mIDH1 peptides survived longer than controls; 25% of them were cured. Immunized mice showed higher amounts of peripheral CD8+ T cells, higher production of IFN-γ, and evidence of anti-mIDH1 antibodies.Immunizations led to intratumoral up-regulation of IFN-γ, granzyme-b and perforin-1 and down-regulation of TGF-β2 and IL-10. These results support the translational potential of immunotherapeutic targeting of gliomas carrying IDH1 mutations.

  3. Reproductive performance in East Greenland polar bears (Ursus maritimus) may be affected by organohalogen contaminants as shown by physiologically-based pharmacokinetic (PBPK) modelling

    DEFF Research Database (Denmark)

    Sonne, Christian; Gustavson, Kim; Rigét, Frank F.

    2009-01-01

    Polar bears (Ursus maritimus) feed mainly on ringed seal (Phoca hispida) and consume large quantities of blubber and consequently have one of the highest tissue concentrations of organohalogen contaminants (OHCs) worldwide. In East Greenland, studies of OHC time trends and organ system health eff...

  4. Evolutionary Accessibility of Mutational Pathways

    Science.gov (United States)

    Franke, Jasper; Klözer, Alexander; de Visser, J. Arjan G. M.; Krug, Joachim

    2011-01-01

    Functional effects of different mutations are known to combine to the total effect in highly nontrivial ways. For the trait under evolutionary selection (‘fitness’), measured values over all possible combinations of a set of mutations yield a fitness landscape that determines which mutational states can be reached from a given initial genotype. Understanding the accessibility properties of fitness landscapes is conceptually important in answering questions about the predictability and repeatability of evolutionary adaptation. Here we theoretically investigate accessibility of the globally optimal state on a wide variety of model landscapes, including landscapes with tunable ruggedness as well as neutral ‘holey’ landscapes. We define a mutational pathway to be accessible if it contains the minimal number of mutations required to reach the target genotype, and if fitness increases in each mutational step. Under this definition accessibility is high, in the sense that at least one accessible pathway exists with a substantial probability that approaches unity as the dimensionality of the fitness landscape (set by the number of mutational loci) becomes large. At the same time the number of alternative accessible pathways grows without bounds. We test the model predictions against an empirical 8-locus fitness landscape obtained for the filamentous fungus Aspergillus niger. By analyzing subgraphs of the full landscape containing different subsets of mutations, we are able to probe the mutational distance scale in the empirical data. The predicted effect of high accessibility is supported by the empirical data and is very robust, which we argue reflects the generic topology of sequence spaces. Together with the restrictive assumptions that lie in our definition of accessibility, this implies that the globally optimal configuration should be accessible to genome wide evolution, but the repeatability of evolutionary trajectories is limited owing to the presence of a

  5. Efficacy and Molecular Mechanisms of Differentiated Response to the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Preclinical Models of p53-Mutated Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Anastasia A. Ionkina

    2017-05-01

    Full Text Available PurposeTriple-negative breast cancer (TNBC is a subtype associated with poor prognosis and for which there are limited therapeutic options. The purpose of this study was to evaluate the efficacy of ENMD-2076 in p53-mutated TNBC patient-derived xenograft (PDX models and describe patterns of terminal cell fate in models demonstrating sensitivity, intrinsic resistance, and acquired resistance to ENMD-2076.Experimental designp53-mutated, TNBC PDX models were treated with ENMD-2076 and evaluated for mechanisms of sensitivity or resistance to treatment. Correlative tissue testing was performed on tumor tissue to assess for markers of proliferation, apoptosis, senescence, and pathways of resistance after treatment and at the time of acquired resistance.ResultsSensitivity to ENMD-2076 200 mg/kg daily was associated with induction of apoptosis while models exhibiting intrinsic or acquired resistance to treatment presented with a senescent phenotype. Response to ENMD-2076 was accompanied by an increase in p53 and p73 levels, even within the background of mutant p53. Treatment with ENMD-2076 resulted in a decrease in pAurA and an increase in pHH3. We observed a TNBC subtype switch from the luminal androgen receptor to the basal-like subtype at acquired resistance.ConclusionENMD-2076 has antitumor activity in preclinical models of p53-mutated TNBC. Increased levels of p53 and p73 correlated with sensitivity whereas senescence was associated with resistance to ENMD-2076. The novel finding of a TNBC subtype switch at time of acquired resistance may provide mechanistic insights into the biologic effects of selective pressure of anticancer treatments on TNBC. ENMD-2076 is currently being evaluated in a Phase 2 clinical trial in patients with metastatic, previously treated TNBC where these biologic correlates can be further explored.

  6. A Simulation Study of Recessed Type Hydrostatic Journal Bearing

    Directory of Open Access Journals (Sweden)

    Wong Shih-Ming

    2016-01-01

    Full Text Available In this paper, a simulation model is established to study effects of the bearing system parameters on bearing performance. The static performance (such as load capacity, stiffness and flow about various dimensions of multi-recess type hydrostatic journal bearings with constant-resistant restrictor compensation was investigated. The parameters studied includes length/diameter ratio, number of recess, recess length ratio, recess width ratio, initial ratio between recess pressure to supply pressure, and eccentricity.

  7. Compliant hydrodynamic fluid journal bearing

    Science.gov (United States)

    Warren, E. L. (Inventor)

    1985-01-01

    An air bearing structure is described that prevents destructive bending moments within the top foil. Welds are eliminated by mounting the top bearing foil in the bearing cartridge sleeve without using a space block. Tabs or pins at the end of the top bearing foil are restrained by slots or stops formed in the cartridge sleeve. These structural members are free to move in a direction normal to the shaft while being restrained from movement in the direction of shaft rotation.

  8. Active Magnetic Bearings – Magnetic Forces

    DEFF Research Database (Denmark)

    Kjølhede, Klaus

    2006-01-01

    Parameter identification procedures and model validation are major steps towards intelligent machines supported by active magnetic bearings (AMB). The ability of measuring the electromagnetic bearing forces, or deriving them from measuring the magnetic flux, strongly contributes to the model...... of the work is the characterization of magnetic forces by using two experimental different experimental approaches. Such approaches are investigated and described in details. A special test rig is designed where the 4 poles - AMB is able to generate forces up to 1900 N. The high precision characterization...... of the magnetic forces are led by using different experimental tests: (I) by using hall sensors mounted directly on the poles (precise measurements of the magnetic flux) and by an auxiliary system, composed of strain gages and flexible beams attached to the rotor; (II) by measuring the input current and bearing...

  9. Magnetic bearing and motor

    Science.gov (United States)

    Studer, Philip A. (Inventor)

    1983-01-01

    A magnetic bearing assembly (10) has an intermediate rotatable section (33) having an outer cylindrical member (30) coaxially suspended by a torsion wire (72) around an axially polarized cylindrical magnet (32). Axial alignment between the pole faces (40-43) of the intermediate section (33) and end surfaces (50-53) of opposed end bells (20, 22) provides a path of least reluctance across intervening air gaps (60-63) for the magnetic flux emanating from magnet (32). Radial dislocation increases the reluctance and creates a radial restoring force. Substitution of radially polarized magnets 107 fixed to a magnetically permeable cylinder (32') and insertion of pairs of armature coil windings (109-112) between the cylinder pair (33') provides an integral magnetic bearing and torsion motor (100) able to provide arcuately limited rotational drive.

  10. Passive magnetic bearing system

    Science.gov (United States)

    Post, Richard F.

    2014-09-02

    An axial stabilizer for the rotor of a magnetic bearing provides external control of stiffness through switching in external inductances. External control also allows the stabilizer to become a part of a passive/active magnetic bearing system that requires no external source of power and no position sensor. Stabilizers for displacements transverse to the axis of rotation are provided that require only a single cylindrical Halbach array in its operation, and thus are especially suited for use in high rotation speed applications, such as flywheel energy storage systems. The elimination of the need of an inner cylindrical array solves the difficult mechanical problem of supplying support against centrifugal forces for the magnets of that array. Compensation is provided for the temperature variation of the strength of the magnetic fields of the permanent magnets in the levitating magnet arrays.

  11. Government Risk-Bearing

    CERN Document Server

    1993-01-01

    The u.s. government bulks large in the nation's financial markets. The huge volume of government-issued and -sponsored debt affects the pricing and volume ofprivate debt and, consequently, resource allocation between competing alternatives. What is often not fully appreciated is the substantial influence the federal government wields overresource allocation through its provisionofcreditandrisk-bearing services to the private economy. Because peopleand firms generally seekto avoid risk, atsomeprice they are willing to pay another party to assume the risk they would otherwise face. Insurance companies are a class of private-sector firms one commonly thinks of as providing these services. As the federal government has expanded its presence in the U.S. economy during this century, it has increasingly developed programs aimed at bearing risks that the private sector either would not take on at any price, or would take on but atapricethoughtto besogreatthatmostpotentialbeneficiarieswouldnotpurchase the coverage. To...

  12. COMPOSITION OF BLACK BEAR MILK.

    Science.gov (United States)

    An analysis of black bear ( Ursus americanus Pallas) milk showed that the total solids, fat and protein were much higher and the lactose lower than...either cow or human milk. In comparison with polar bear (Thalarcotos maritimus ), the black bear milk was lower in fat, protein and total calories. (Author)

  13. Frictionless Bearing Uses Permanent Magnets

    Science.gov (United States)

    1965-01-01

    The purpose of this innovation was to develop a frictionless bearing for high speed, light load applications. The device involves the incorporation of permanent magnets in the bearing design. The repulsion of like magnetic poles provides concentric support of the inner member so that no metallic contact occurs between the bearing surfaces.

  14. Rotating plug bearing and seal

    International Nuclear Information System (INIS)

    Wade, E.E.

    1977-01-01

    Disclosed is a bearing and seal structure for nuclear reactors utilizing rotating plugs above the nuclear reactor vessel. The structure permits lubrication of bearings and seals of the rotating plugs without risk of the lubricant draining into the reactor vessel below. The structure permits lubrication by utilizing a rotating outer race bearing. 19 claims, 3 figures

  15. Research on variational mode decomposition in rolling bearings fault diagnosis of the multistage centrifugal pump

    Science.gov (United States)

    Zhang, Ming; Jiang, Zhinong; Feng, Kun

    2017-09-01

    Rolling bearing faults are among the primary causes of breakdown in multistage centrifugal pump. A novel method of rolling bearings fault diagnosis based on variational mode decomposition is presented in this contribution. The rolling bearing fault signal calculating model of different location defect is established by failure mechanism analysis, and the simulation vibration signal of the proposed fault model is investigated by FFT and envelope analysis. A comparison has gone to evaluate the performance of bearing defect characteristic extraction for rolling bearings simulation signal by using VMD and EMD. The result of comparison verifies the VMD can accurately extract the principal mode of bearing fault signal, and it better than EMD in bearing defect characteristic extraction. The VMD is then applied to detect different location fault features for rolling bearings fault diagnosis via modeling simulation vibration signal and practical vibration signal. The analysis result of simulation and experiment proves that the proposed method can successfully diagnosis rolling bearings fault.

  16. Effects of tooth profile modification on dynamic responses of a high speed gear-rotor-bearing system

    Science.gov (United States)

    Hu, Zehua; Tang, Jinyuan; Zhong, Jue; Chen, Siyu; Yan, Haiyan

    2016-08-01

    A finite element node dynamic model of a high speed gear-rotor-bearing system considering the time-varying mesh stiffness, backlash, gyroscopic effect and transmission error excitation is developed. Different tooth profile modifications are introduced into the gear pair and corresponding time-varying mesh stiffness curves are obtained. Effects of the tooth profile modification on mesh stiffness are analyzed, and the natural frequencies and mode shapes of the gear-rotor-bearing transmission system are given. The dynamic responses with respect to a wide input speed region including dynamic factor, vibration amplitude near the bearing and dynamic transmission error are obtained by introducing the time-varying mesh stiffness in different tooth profile modification cases into the gear-rotor-bearing dynamic system. Effects of the tooth profile modification on the dynamic responses are studied in detail. The numerical simulation results show that both the short profile modification and the long profile modification can affect the mutation of the mesh stiffness when the number of engaging tooth pairs changes. A short profile modification with an appropriate modification amount can improve the dynamic property of the system in certain work condition.

  17. Radium bearing waste disposal

    International Nuclear Information System (INIS)

    Tope, W.G.; Nixon, D.A.; Smith, M.L.; Stone, T.J.; Vogel, R.A.; Schofield, W.D.

    1995-01-01

    Fernald radium bearing ore residue waste, stored within Silos 1 and 2 (K-65) and Silo 3, will be vitrified for disposal at the Nevada Test Site (NTS). A comprehensive, parametric evaluation of waste form, packaging, and transportation alternatives was completed to identify the most cost-effective approach. The impacts of waste loading, waste form, regulatory requirements, NTS waste acceptance criteria, as-low-as-reasonably-achievable principles, and material handling costs were factored into the recommended approach

  18. Biodistribution, pharmacokinetics and PET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc in a sarcoma- and inflammation-bearing mouse model.

    Science.gov (United States)

    Liu, Ren-Shyan; Chou, Ta-Kai; Chang, Chih-Hsien; Wu, Chun-Yi; Chang, Chi-Wei; Chang, Tsui-Jung; Wang, Shih-Jen; Lin, Wuu-Jyh; Wang, Hsin-Ell

    2009-04-01

    2-Deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG), [(18)F]fluoroacetate ([(18)F]FAc) and [(18)F]fluoromisonidazole ([(18)F]FMISO) were all considered to be positron emission tomography (PET) probes for tumor diagnosis, though based on different rationale of tissue uptake. This study compared the biodistribution, pharmacokinetics and imaging of these three tracers in a sarcoma- and inflammation-bearing mouse model. C3H mice were inoculated with 2x10(5) KHT sarcoma cells in the right thigh on Day 0. Turpentine oil (0.1 ml) was injected in the left thigh on Day 11 to induce inflammatory lesion. Biodistribution, pharmacokinetics and microPET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc were performed on Day 14 after tumor inoculation. The inflammatory lesions were clearly visualized by [(18)F]FDG/microPET and autoradiography at 3 days after turpentine oil injection. The tumor-to-muscle and inflammatory lesion-to-muscle ratios derived from microPET imaging were 6.79 and 1.48 for [(18)F]FMISO, 8.12 and 4.69 for [(18)F]FDG and 3.72 and 3.19 for [(18)F]FAc at 4 h post injection, respectively. Among these, the tumor-to-inflammation ratio was the highest (4.57) for [(18)F]FMISO compared with that of [(18)F]FDG (1.73) and [(18)F]FAc (1.17), whereas [(18)F]FAc has the highest bioavailability (area under concentration of radiotracer vs. time curve, 116.2 hxpercentage of injected dose per gram of tissue). MicroPET images and biodistribution studies showed that the accumulation of [(18)F]FMISO in the tumor is significantly higher than that in inflammatory lesion at 4 h post injection. [(18)F]FDG and [(18)F]FAc delineated both tumor and inflammatory lesions. Our results demonstrated the potential of [(18)F]FMISO/PET in distinguishing tumor from inflammatory lesion.

  19. Mutation discovery in regions of segmental cancer genome amplifications with CoNAn-SNV: a mixture model for next generation sequencing of tumors.

    Science.gov (United States)

    Crisan, Anamaria; Goya, Rodrigo; Ha, Gavin; Ding, Jiarui; Prentice, Leah M; Oloumi, Arusha; Senz, Janine; Zeng, Thomas; Tse, Kane; Delaney, Allen; Marra, Marco A; Huntsman, David G; Hirst, Martin; Aparicio, Sam; Shah, Sohrab

    2012-01-01

    Next generation sequencing has now enabled a cost-effective enumeration of the full mutational complement of a tumor genome-in particular single nucleotide variants (SNVs). Most current computational and statistical models for analyzing next generation sequencing data, however, do not account for cancer-specific biological properties, including somatic segmental copy number alterations (CNAs)-which require special treatment of the data. Here we present CoNAn-SNV (Copy Number Annotated SNV): a novel algorithm for the inference of single nucleotide variants (SNVs) that overlap copy number alterations. The method is based on modelling the notion that genomic regions of segmental duplication and amplification induce an extended genotype space where a subset of genotypes will exhibit heavily skewed allelic distributions in SNVs (and therefore render them undetectable by methods that assume diploidy). We introduce the concept of modelling allelic counts from sequencing data using a panel of Binomial mixture models where the number of mixtures for a given locus in the genome is informed by a discrete copy number state given as input. We applied CoNAn-SNV to a previously published whole genome shotgun data set obtained from a lobular breast cancer and show that it is able to discover 21 experimentally revalidated somatic non-synonymous mutations in a lobular breast cancer genome that were not detected using copy number insensitive SNV detection algorithms. Importantly, ROC analysis shows that the increased sensitivity of CoNAn-SNV does not result in disproportionate loss of specificity. This was also supported by analysis of a recently published lymphoma genome with a relatively quiescent karyotype, where CoNAn-SNV showed similar results to other callers except in regions of copy number gain where increased sensitivity was conferred. Our results indicate that in genomically unstable tumors, copy number annotation for SNV detection will be critical to fully characterize the

  20. The G46S-hPAH mutant protein: a model to study the rescue of aggregation-prone PKU mutations by chaperones.

    Science.gov (United States)

    Leandro, João; Saraste, Jaakko; Leandro, Paula; Flatmark, Torgeir

    2011-01-01

    Phenylketonuria (PKU), the most common inborn error of metabolism, is caused by dysfunction of the liver enzyme phenylalanine hydroxylase (PAH), with more than 550 PAH gene mutations identified to date. A large number of these mutations result in mutant forms of the enzyme displaying reduced stability, increased propensity to aggregate, and accelerated in cellulo degradation. Loss or reduction of human PAH activity results in hyperphenylalaninemia (HPA) which, if untreated, results in severe mental retardation and impaired cognitive development. Until now, strict low phenylalanine diet has been the most effective therapy, but as a protein misfolding disease PKU is a good candidate for treatment by natural/chemical/pharmacological chaperones. The natural cofactor of human PAH, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)), has already been approved for oral treatment of HPA, giving a positive response in mild forms of the disease showing considerable residual enzymatic activity. In the case of the most severe forms of PKU, ongoing studies with chemical and pharmacological chaperones to rescue misfolded mutant proteins from aggregation and degradation are providing promising results. The PKU mutation G46S is associated with a severe form of the disease, resulting in an aggregation-prone protein. The human PAH mutant G46S is rapidly degraded in the cellular environment and, in vitro (upon removal of its stabilizing fusion partner maltose binding protein (MBP)) self-associates to form higher-order oligomers/fibrils. Here, we present an in vitro experimental model system to study the modulation of G46S aggregation by chemical/pharmacological chaperones, which may represent a useful approach to study the rescue of other severe PKU mutations by chemical/pharmacological chaperones. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. KRAS exon 2 mutations influence activity of regorafenib in an SW48-based disease model of colorectal cancer.

    Science.gov (United States)

    Camaj, Peter; Primo, Stefano; Wang, Yan; Heinemann, Volker; Zhao, Yue; Laubender, Ruediger Paul; Stintzing, Sebastian; Giessen-Jung, Clemens; Jung, Andreas; Gamba, Sebastian; Bruns, Christiane Josephine; Modest, Dominik Paul

    2015-01-01

    To investigate the impact of KRAS mutation variants on the activity of regorafenib in SW48 colorectal cancer cells. Activity of regorafenib was evaluated in isogenic SW48 KRAS wild-type (WT) and mutant cells. Subcutaneous xenografts (KRAS WT and G12C mutant variants) in NOD/SCID mice were analyzed to elucidate the effect of regorafenib treatment in vivo. Compared with KRAS WT cells, all mutant variants seemed associated with some degree of resistance to regorafenib-treatment in vitro. In vivo, activation of apoptosis (TUNEL) and reduction of proliferation (Ki67) after treatment with regorafenib were more pronounced in KRAS WT tumors as compared with G12C variants. In SW48 cells, exon 2 mutations of the KRAS gene may influence antitumor effects of regorafenib.

  2. Dynamics of Mutator and Antibiotic-Resistant Populations in a Pharmacokinetic/Pharmacodynamic Model of Pseudomonas aeruginosa Biofilm Treatment

    DEFF Research Database (Denmark)

    Macià, María D.; Pérez, José L.; Molin, Søren

    2011-01-01

    tagged PAO1 and PAOMS (mutator [mutS] derivative) strains. Two-day-old biofilms were treated with ciprofloxacin (CIP) for 4 days (t4) at 2 µg/ml, which correlated with the mutant prevention concentration (MPC) and provided an AUC/MIC ratio of 384 that should predict therapeutic success. Biofilms were...... monitored by confocal laser scanning microscopy (CLSM), and the numbers of viable cells and resistant mutants (4- and 16-fold MICs) were determined. Despite optimized pharmacokinetic/pharmacodynamic (PK/PD) parameters, CIP treatment did not suppress resistance development in P. aeruginosa biofilms. One.......01 proportion, took over the whole biofilm after only 2 days of CIP treatment outnumbering PAO1 by 3 log at t4. Our results show that mutational mechanisms play a major role in biofilm antibiotic resistance and that theoretically optimized PK/PD parameters fail to suppress resistance development, suggesting...

  3. Inducing Somatic Pkd1 Mutations in Vivo in a Mouse Model of Autosomal-Dominant Polycystic Kidney Disease

    Science.gov (United States)

    2016-10-01

    inducing homozygous mutations of Pkd2 during embryonic kidney development . Specifically, the Six2cre enhancer drives the expression of cre in the...Cristina Cebrian-Ligero Funded Period : July 15, 2016 to July 14, 2017 Amount: $40,000 What other organizations were involved as partners? No change...Disease PRINCIPAL INVESTIGATOR: Cristina Cebrian-Ligero CONTRACTING ORGANIZATION : Regents of the University of Michigan Ann Arbor, MI, 48109-1340

  4. Using Drosophila melanogaster as a model for genotoxic chemical mutational studies with a new program, SnpSift

    Directory of Open Access Journals (Sweden)

    Douglas Mark Ruden

    2012-03-01

    Full Text Available This paper describes a new program SnpSift for filtering differential DNA sequence variants between two or more experimental genomes after genotoxic chemical exposure. Here, we illustrate how SnpSift can be used to identify candidate phenotype-relevant variants including single nucleotide polymorphisms (SNPs, multiple nucleotide polymorphisms (MNPs, insertions and deletions (InDels in mutant strains isolated from genome-wide chemical mutagenesis of Drosophila melanogaster. First, the genomes of two independently-isolated mutant fly strains that are allelic for a novel recessive male-sterile locus generated by genotoxic chemical exposure were sequenced using the Illumina next-generation DNA sequencer to obtain 20- to 29-fold coverage of the euchromatic sequences. The sequencing reads were processed and variants were called using standard bioinformatic tools. Next, SnpEff was used to annotate all sequence variants and their potential mutational effects on associated genes. Then, SnpSift was used to filter and select differential variants that potentially disrupt a common gene in the two allelic mutant strains. The potential causative DNA lesions were partially validated by capillary sequencing of PCR-amplified DNA in the genetic interval as defined by meiotic mapping and deletions that remove defined regions of the chromosome. Of the five candidate genes located in the genetic interval, the Pka-like gene CG12069 was found to carry a separate premature stop codon mutation in each of the two allelic mutants whereas the other 4 candidate genes within the interval have wild-type sequences. The Pka-like gene is therefore a strong candidate gene for the male-sterile locus. These results demonstrate that combining SnpEff and SnpSift can expedite the identification of candidate phenotype-causative mutations in chemically-mutagenized Drosophila strains. This technique can also be used to characterize the variety of mutations generated by genotoxic

  5. Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model

    Directory of Open Access Journals (Sweden)

    Guenther Simone M

    2007-03-01

    Full Text Available Abstract Background microRNAs (miRNAs are a group of non-coding single stranded RNAs measuring approximately 22 nucleotides in length that have been found to control cell growth, differentiation and apoptosis. They negatively regulate target genes and have recently been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. Recently, a point mutation in the BRAF gene leading to a V600E substitution has been identified as the most common genetic change in papillary thyroid carcinoma (PTC occurring in 29–69% of cases. This mutation leads to aberrant MAPK activation that is implicated in tumourigenesis. Aim The aim of this study was to identify the effect that BRAF oncogene has on post-transcriptional regulation in PTC by using microRNA analysis. Results A unique miRNA expression signature differentiated between PTC cell lines with BRAF mutations and a normal thyroid cell line. 15 miRNAs were found to be upregulated and 23 miRNAs were downregulated. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis. miRNA profiling will assist in the elucidation of disease pathogenesis and identification biomarkers and targets.

  6. Bearing for liquid metal pump

    International Nuclear Information System (INIS)

    Dickinson, R.J.; Pennell, W.E.; Wasko, J.

    1984-01-01

    A liquid metal pump bearing support comprises a series of tangentially oriented spokes that connect the bearing cylinder to the pump internals structure. The spokes may be arranged in a plurality of planes extending from the bearing cylinder to the pump internals with the spokes in one plane being arranged alternately with those in the next plane. The bearing support structure provides the pump with sufficient lateral support for the bearing structure together with the capability of accommodating differential thermal expansion without adversely affecting pump performance

  7. Bearing, gearing, and lubrication technology

    Science.gov (United States)

    Anderson, W. J.

    1978-01-01

    Results of selected NASA research programs on rolling-element and fluid-film bearings, gears, and elastohydrodynamic lubrication are reported. Advances in rolling-element bearing material technology, which have resulted in a significant improvement in fatigue life, and which make possible new applications for rolling bearings, are discussed. Research on whirl-resistant, fluid-film bearings, suitable for very high-speed applications, is discussed. An improved method for predicting gear pitting life is reported. An improved formula for calculating the thickness of elastohydrodynamic films (the existence of which help to define the operating regime of concentrated contact mechanisms such as bearings, gears, and cams) is described.

  8. Aphid thermal tolerance is governed by a point mutation in bacterial symbionts.

    Directory of Open Access Journals (Sweden)

    Helen E Dunbar

    2007-05-01

    Full Text Available Symbiosis is a ubiquitous phenomenon generating biological complexity, affecting adaptation, and expanding ecological capabilities. However, symbionts, which can be subject to genetic limitations such as clonality and genomic degradation, also impose constraints on hosts. A model of obligate symbiosis is that between aphids and the bacterium Buchnera aphidicola, which supplies essential nutrients. We report a mutation in Buchnera of the aphid Acyrthosiphon pisum that recurs in laboratory lines and occurs in field populations. This single nucleotide deletion affects a homopolymeric run within the heat-shock transcriptional promoter for ibpA, encoding a small heat-shock protein. This Buchnera mutation virtually eliminates the transcriptional response of ibpA to heat stress and lowers its expression even at cool or moderate temperatures. Furthermore, this symbiont mutation dramatically affects host fitness in a manner dependent on thermal environment. Following a short heat exposure as juveniles, aphids bearing short-allele symbionts produced few or no progeny and contained almost no Buchnera, in contrast to aphids bearing symbionts without the deletion. Conversely, under constant cool conditions, aphids containing symbionts with the short allele reproduced earlier and maintained higher reproductive rates. The short allele has appreciable frequencies in field populations (up to 20%, further supporting the view that lowering of ibpA expression improves host fitness under some conditions. This recurring Buchnera mutation governs thermal tolerance of aphid hosts. Other cases in which symbiont microevolution has a major effect on host ecological tolerance are likely to be widespread because of the high mutation rates of symbiotic bacteria and their crucial roles in host metabolism and development.

  9. Food availability and foraging near human developments by black bears

    Science.gov (United States)

    Merkle, Jerod A.; Robinson, Hugh S.; Krausman, Paul R.; Alaback, Paul B.

    2013-01-01

    Understanding the relationship between foraging ecology and the presence of human-dominated landscapes is important, particularly for American black bears (Ursus americanus), which sometimes move between wildlands and urban areas to forage. The food-related factors influencing this movement have not been explored, but can be important for understanding the benefits and costs to black bear foraging behavior and the fundamental origins of bear conflicts. We tested whether the scarcity of wildland foods or the availability of urban foods can explain when black bears forage near houses, examined the extent to which male bears use urban areas in comparison to females, and identified the most important food items influencing bear movement into urban areas. We monitored 16 collared black bears in and around Missoula, Montana, during 2009 and 2010, while quantifying the rate of change in green vegetation and the availability of 5 native berry-producing species outside the urban area, the rate of change in green vegetation, and the availability of apples and garbage inside the urban area. We used parametric time-to-event models in which an event was a bear location collected within 100 m of a house. We also visited feeding sites located near houses and quantified food items bears had eaten. The probability of a bear being located near a house was 1.6 times higher for males, and increased during apple season and the urban green-up. Fruit trees accounted for most of the forage items at urban feeding sites (49%), whereas wildland foods composed Black bears foraged on human foods near houses even when wildland foods were available, suggesting that the absence of wildland foods may not influence the probability of bears foraging near houses. Additionally, other attractants, in this case fruit trees, appear to be more important than the availability of garbage in influencing when bears forage near houses.

  10. Interaction of Reinforced Elastomeric Bearings in Bridge Construction

    Directory of Open Access Journals (Sweden)

    Nittmannová Ľubica

    2016-03-01

    Full Text Available The aim of this paper is to demonstrate the behavior of reinforced elastomeric bearings under various loads. They are made of special types of bearings. The experimental verification of these special bearings has been tested on various types of loading. The results of the experimental measurements are compared with the results of the numerical modeling and calculations according to the standard assumptions in STN EN 1337-3. In the conclusion, the results are summarized for the selected types of bearings.

  11. Gearbox Reliability Collaborative Gearbox 3 Planet Bearing Calibration

    Energy Technology Data Exchange (ETDEWEB)

    Keller, Jonathan [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2017-03-24

    The Gearbox Reliability Collaborative gearbox was redesigned to improve its load-sharing characteristics and predicted fatigue life. The most important aspect of the redesign was to replace the cylindrical roller bearings with preloaded tapered roller bearings in the planetary section. Similar to previous work, the strain gages installed on the planet tapered roller bearings were calibrated in a load frame. This report describes the calibration tests and provides the factors necessary to convert the measured units from dynamometer testing to bearing loads, suitable for comparison to engineering models.

  12. Development and test of model apparatus of non-contact spin processor for photo mask production applying radial-type superconducting magnetic bearing

    International Nuclear Information System (INIS)

    Saito, Kimiyo; Fukui, Satoshi; Maezawa, Masaru; Ogawa, Jun; Oka, Tetsuo; Sato, Takao

    2013-01-01

    Highlights: ► We develop test spinner for non-contact spinning process in photo mask production. ► This test spinner shows improved spinning ability compared with our previous one. ► Large vertical movement of turn table still occurs during acceleration. ► Method to control vertical movement of turn table should be developed in next step. -- Abstract: In semiconductor devices, miniaturization of circuit patterning on wafers is required for higher integrations of circuit elements. Therefore, very high tolerance and quality are also required for patterning of microstructures of photo masks. The deposition of particulate dusts generated from mechanical bearings of the spin processor in the patterns of the photo mask is one of main causes of the deterioration of pattern preciseness. In our R and D, application of magnetic bearing utilizing bulk high temperature superconductors to the spin processors has been proposed. In this study, we develop a test spinner for the non-contact spinning process in the photo mask production system. The rotation test by using this test spinner shows that this test spinner accomplishes the improvement of the spinning ability compared with the test spinner developed in our previous study. This paper describes the rotation test results of the new test spinner applying the magnetic bearing with bulk high temperature superconductors

  13. An impulsive receptance technique for the time domain computation of the vibration of a whole aero-engine model with nonlinear bearings

    Science.gov (United States)

    Hai, Pham Minh; Bonello, Philip

    2008-12-01

    The direct study of the vibration of real engine structures with nonlinear bearings, particularly aero-engines, has been severely limited by the fact that current nonlinear computational techniques are not well-suited for complex large-order systems. This paper introduces a novel implicit "impulsive receptance method" (IRM) for the time domain analysis of such structures. The IRM's computational efficiency is largely immune to the number of modes used and dependent only on the number of nonlinear elements. This means that, apart from retaining numerical accuracy, a much more physically accurate solution is achievable within a short timeframe. Simulation tests on a realistically sized representative twin-spool aero-engine showed that the new method was around 40 times faster than a conventional implicit integration scheme. Preliminary results for a given rotor unbalance distribution revealed the varying degree of journal lift, orbit size and shape at the example engine's squeeze-film damper bearings, and the effect of end-sealing at these bearings.

  14. Progressive Aggregation of Alpha-Synuclein and Selective Degeneration of Lewy Inclusion-Bearing Neurons in a Mouse Model of Parkinsonism

    Directory of Open Access Journals (Sweden)

    Valerie R. Osterberg

    2015-03-01

    Full Text Available Aggregated alpha-synuclein inclusions are found where cell death occurs in several diseases, including Parkinson’s disease, dementia with Lewy bodies, and multiple-system atrophy. However, the relationship between inclusion formation and an individual cell’s fate has been difficult to study with conventional techniques. We developed a system that allows for in vivo imaging of the same neurons over months. We show that intracerebral injection of preformed fibrils of recombinant alpha-synuclein can seed aggregation of transgenically expressed and endogenous alpha-synuclein in neurons. Somatic inclusions undergo a stage-like maturation, with progressive compaction coinciding with decreased soluble somatic and nuclear alpha-synuclein. Mature inclusions bear the post-translational hallmarks of human Lewy pathology. Long-term imaging of inclusion-bearing neurons and neighboring neurons without inclusions demonstrates selective degeneration of inclusion-bearing cells. Our results indicate that inclusion formation is tightly correlated with cellular toxicity and that seeding may be a pathologically relevant mechanism of progressive neurodegeneration in many synucleinopathies.

  15. Bearing construction for refrigeration compresssor

    Science.gov (United States)

    Middleton, Marc G.; Nelson, Richard T.

    1988-01-01

    A hermetic refrigeration compressor has a cylinder block and a crankshaft rotatable about a vertical axis to reciprocate a piston in a cylinder on the cylinder block. A separate bearing housing is secured to the central portion of the cylinder block and extends vertically along the crankshaft, where it carries a pair of roller bearings to journal the crankshaft. The crankshaft has a radially extending flange which is journaled by a thrust-type roller bearing above the bearing housing to absorb the vertical forces on the crankshaft so that all three of the roller bearings are between the crankshaft and the bearing housing to maintain and control the close tolerances required by such bearings.

  16. 77 FR 70423 - Black Bear Hydro Partners, LLC and Black Bear Development Holdings, LLC and Black Bear SO, LLC...

    Science.gov (United States)

    2012-11-26

    ... Bear Hydro Partners, LLC and Black Bear Development Holdings, LLC and Black Bear SO, LLC; Notice of..., 2012, Black Bear Hydro Partners, LLC, sole licensee (transferor) and Black Bear Development Holdings, LLC and Black Bear SO, LLC (transferees) filed an application for the partial the transfer of licenses...

  17. Numerical investigation of cavitation flow in journal bearing geometry

    Directory of Open Access Journals (Sweden)

    Stücke P.

    2013-04-01

    Full Text Available The appearance of cavitation is still a problem in technical and industrial applications. Especially in automotive internal combustion engines, hydrodynamic journal bearings are used due to their favourable wearing quality and operating characteristics. Cavitation flows inside the bearings reduces the load capacity and leads to a risk of material damages. Therefore an understanding of the complex flow phenomena inside the bearing is necessary for the design development of hydrodynamic journal bearings. Experimental investigations in the fluid domain of the journal bearing are difficult to realize founded by the small dimensions of the bearing. In the recent years more and more the advantages of the computational fluid dynamics (CFD are used to investigate the detail of the cavitation flows. The analysis in the paper is carried out in a two-step approach. At first an experimental investigation of journal bearing including cavitation is selected from the literature. The complex numerical model validated with the experimental measured data. In a second step, typically design parameters, such as a groove and feed hole, which are necessary to distribute the oil supply across the gap were added into the model. The paper reflects on the influence of the used design parameters and the variation of the additional supply flow rate through the feed hole regarding to cavitation effects in the bearing. Detailed pictures of the three-dimensional flow structures and the cavitation regions inside the flow film of the bearing are presented.

  18. Numerical investigation of cavitation flow in journal bearing geometry

    Science.gov (United States)

    Riedel, M.; Schmidt, M.; Stücke, P.

    2013-04-01

    The appearance of cavitation is still a problem in technical and industrial applications. Especially in automotive internal combustion engines, hydrodynamic journal bearings are used due to their favourable wearing quality and operating characteristics. Cavitation flows inside the bearings reduces the load capacity and leads to a risk of material damages. Therefore an understanding of the complex flow phenomena inside the bearing is necessary for the design development of hydrodynamic journal bearings. Experimental investigations in the fluid domain of the journal bearing are difficult to realize founded by the small dimensions of the bearing. In the recent years more and more the advantages of the computational fluid dynamics (CFD) are used to investigate the detail of the cavitation flows. The analysis in the paper is carried out in a two-step approach. At first an experimental investigation of journal bearing including cavitation is selected from the literature. The complex numerical model validated with the experimental measured data. In a second step, typically design parameters, such as a groove and feed hole, which are necessary to distribute the oil supply across the gap were added into the model. The paper reflects on the influence of the used design parameters and the variation of the additional supply flow rate through the feed hole regarding to cavitation effects in the bearing. Detailed pictures of the three-dimensional flow structures and the cavitation regions inside the flow film of the bearing are presented.

  19. Introgressive hybridization: brown bears as vectors for polar bear alleles.

    Science.gov (United States)

    Hailer, Frank

    2015-03-01

    The dynamics and consequences of introgression can inform about numerous evolutionary processes. Biologists have therefore long been interested in hybridization. One challenge, however, lies in the identification of nonadmixed genotypes that can serve as a baseline for accurate quantification of admixture. In this issue of Molecular Ecology, Cahill et al. (2015) analyse a genomic data set of 28 polar bears, eight brown bears and one American black bear. Polar bear alleles are found to be introgressed into brown bears not only near a previously identified admixture zone on the Alaskan Admiralty, Baranof and Chichagof (ABC) Islands, but also far into the North American mainland. Elegantly contrasting admixture levels at autosomal and X chromosomal markers, Cahill and colleagues infer that male-biased dispersal has spread these introgressed alleles away from the Late Pleistocene contact zone. Compared to a previous study on the ABC Island population in which an Alaskan brown bear served as a putatively admixture-free reference, Cahill et al. (2015) utilize a newly sequenced Swedish brown bear as admixture baseline. This approach reveals that brown bears have been impacted by introgression from polar bears to a larger extent (up to 8.8% of their genome), than previously known, including the bear that had previously served as admixture baseline. No evidence for introgression of brown bear into polar bear is found, which the authors argue could be a consequence of selection. Besides adding new exciting pieces to the puzzle of polar/brown bear evolutionary history, the study by Cahill and colleagues highlights that wildlife genomics is moving from analysing single genomes towards a landscape genomics approach. © 2015 John Wiley & Sons Ltd.

  20. Thermo-hydrodynamic lubrication in hydrodynamic bearings

    CERN Document Server

    Bonneau, Dominique; Souchet, Dominique

    2014-01-01

    This Series provides the necessary elements to the development and validation of numerical prediction models for hydrodynamic bearings. This book describes the thermo-hydrodynamic and the thermo-elasto-hydrodynamic lubrication. The algorithms are methodically detailed and each section is thoroughly illustrated.

  1. Radiation-induced total-deletion mutations in the human hprt gene: a biophysical model based on random walk interphase chromatin geometry

    Science.gov (United States)

    Wu, H.; Sachs, R. K.; Yang, T. C.

    1998-01-01

    PURPOSE: To develop a biophysical model that explains the sizes of radiation-induced hprt deletions. METHODS: Key assumptions: (1) Deletions are produced by two DSB that are closer than an interaction distance at the time of DSB induction; (2) Interphase chromatin is modelled by a biphasic random walk distribution; and (3) Misrejoining of DSB from two separate tracks dominates at low-LET and misrejoining of DSB from a single track dominates at high-LET. RESULTS: The size spectra for radiation-induced total deletions of the hprt gene are calculated. Comparing with the results of Yamada and coworkers for gamma-irradiated human fibroblasts the study finds that an interaction distance of 0.75 microm will fit both the absolute frequency and the size spectrum of the total deletions. It is also shown that high-LET radiations produce, relatively, more total deletions of sizes below 0.5 Mb. The model predicts an essential gene to be located between 2 and 3 Mb from the hprt locus towards the centromere. Using the same assumptions and parameters as for evaluating mutation frequencies, a frequency of intra-arm chromosome deletions is calculated that is in agreement with experimental data. CONCLUSIONS: Radiation-induced total-deletion mutations of the human hprt gene and intrachange chromosome aberrations share a common mechanism for their induction.

  2. Bearing load distribution studies in a multi bearing rotor system and a remote computing method based on the internet

    International Nuclear Information System (INIS)

    Yang, Zhao Jian; Peng, Ze Jun; Kim, Seock Sam

    2004-01-01

    A model in the form of a Bearing Load Distribution (BLD) matrix in the Multi Bearing Rotor System (MBRS) is established by a transfer matrix equation with the consideration of a bearing load, elevation and uniform load distribution. The concept of Bearing Load Sensitivity (BLS) is proposed and matrices for load and elevation sensitivity are obtained. In order to share MBRS design resources on the internet with remote customers, the basic principle of Remote Computing (RC) based on the internet is introduced ; the RC of the BLD and BLS is achieved by Microsoft Active Server Pages (ASP) technology

  3. Acoustic analysis of an induction motor with viscoelastic bearing supports

    NARCIS (Netherlands)

    Tillema, H.G.; Wensing, J.A.; Selamet, Ahmet

    2002-01-01

    The demand for silent bearing applications has resulted in the development of an effective damping layer between the outer ring of a rolling bearing and the surrounding structure. By means of numerical modeling using both FEM and BEM techniques an induction motor for household appliances is

  4. Bears Arouse Interest in Microbiota's Role in Health.

    Science.gov (United States)

    Dill-McFarland, Kimberly A; Suen, Garret; Carey, Hannah V

    2016-04-01

    The first report of the effect of hibernation on the gut microbiota of bears reveals trends both similar and distinct from those found in small hibernators. A model mouse system also suggested possible roles of the microbiota for healthy weight gain and insulin tolerance in bears during their active season. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Analysing the Effect of Mutation on Protein Function and Discovering Potential Inhibitors of CDK4: Molecular Modelling and Dynamics Studies.

    Directory of Open Access Journals (Sweden)

    Nagasundaram N

    Full Text Available The cyclin-dependent kinase 4 (CDK4-cyclin D1 complex plays a crucial role in the transition from the G1 phase to S phase of the cell cycle. Among the CDKs, CDK4 is one of the genes most frequently affected by somatic genetic variations that are associated with various forms of cancer. Thus, because the abnormal function of the CDK4-cyclin D1 protein complex might play a vital role in causing cancer, CDK4 can be considered a genetically validated therapeutic target. In this study, we used a systematic, integrated computational approach to identify deleterious nsSNPs and predict their effects on protein-protein (CDK4-cyclin D1 and protein-ligand (CDK4-flavopiridol interactions. This analysis resulted in the identification of possible inhibitors of mutant CDK4 proteins that bind the conformations induced by deleterious nsSNPs. Using computational prediction methods, we identified five nsSNPs as highly deleterious: R24C, Y180H, A205T, R210P, and R246C. From molecular docking and molecular dynamic studies, we observed that these deleterious nsSNPs affected CDK4-cyclin D1 and CDK4-flavopiridol interactions. Furthermore, in a virtual screening approach, the drug 5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDROXYPHENYL _4H_CHROMEN_ 4_ONE displayed good binding affinity for proteins with the mutations R24C or R246C, the drug diosmin displayed good binding affinity for the protein with the mutation Y180H, and the drug rutin displayed good binding affinity for proteins with the mutations A205T and R210P. Overall, this computational investigation of the CDK4 gene highlights the link between genetic variation and biological phenomena in human cancer and aids in the discovery of molecularly targeted therapies for personalized treatment.

  6. Mutations in zebrafish pitx2 model congenital malformations in Axenfeld-Rieger syndrome but do not disrupt left-right placement of visceral organs.

    Science.gov (United States)

    Ji, Yongchang; Buel, Sharleen M; Amack, Jeffrey D

    2016-08-01

    Pitx2 is a conserved homeodomain transcription factor that has multiple functions during embryonic development. Mutations in human PITX2 cause autosomal dominant Axenfeld-Rieger syndrome (ARS), characterized by congenital eye and tooth malformations. Pitx2(-/-) knockout mouse models recapitulate aspects of ARS, but are embryonic lethal. To date, ARS treatments remain limited to managing individual symptoms due to an incomplete understanding of PITX2 function. In addition to regulating eye and tooth development, Pitx2 is a target of a conserved Nodal (TGFβ) signaling pathway that mediates left-right (LR) asymmetry of visceral organs. Based on its highly conserved asymmetric expression domain, the Nodal-Pitx2 axis has long been considered a common denominator of LR development in vertebrate embryos. However, functions of Pitx2 during asymmetric organ morphogenesis are not well understood. To gain new insight into Pitx2 function we used genome editing to create mutations in the zebrafish pitx2 gene. Mutations in the pitx2 homeodomain caused phenotypes reminiscent of ARS, including aberrant development of the cornea and anterior chamber of the eye and reduced or absent teeth. Intriguingly, LR asymmetric looping of the heart and gut was normal in pitx2 mutants. These results suggest conserved roles for Pitx2 in eye and tooth development and indicate Pitx2 is not required for asymmetric looping of zebrafish visceral organs. This work establishes zebrafish pitx2 mutants as a new animal model for investigating mechanisms underlying congenital malformations in ARS and high-throughput drug screening for ARS therapeutics. Additionally, pitx2 mutants present a unique opportunity to identify new genes involved in vertebrate LR patterning. We show Nodal signaling-independent of Pitx2-controls asymmetric expression of the fatty acid elongase elovl6 in zebrafish, pointing to a potential novel pathway during LR organogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Spontaneous asj-2J mutant mouse as a model for generalized arterial calcification of infancy: a large deletion/insertion mutation in the Enpp1 gene.

    Directory of Open Access Journals (Sweden)

    Qiaoli Li

    Full Text Available Generalized arterial calcification of infancy (GACI, an autosomal recessive disorder caused by mutations in the ENPP1 gene, manifests with extensive mineralization of the cardiovascular system. The affected individuals in most cases die within the first year of life, and there is currently no effective treatment for this disorder. In this study, we characterized a spontaneous mutant mouse, asj-2J, as a model for GACI. These mice were identified as part of a phenotypic deviant search in a large-scale production colony of BALB/cJ mice at The Jackson Laboratory. They demonstrated a characteristic gait due to stiffening of the joints, with phenotypic similarity to a previously characterized asj ("ages with stiffened joints" mouse, caused by a missense mutation in the Enpp1 gene. Complementation testing indicated that asj-2J and asj were allelic. PCR-based mutation detection strategy revealed in asj-2J mice a large, 40,035 bp, deletion spanning from intron 1 to the 3'-untranslated region of the Enpp1 gene, coupled with a 74 bp insertion. This was accompanied with a significant reduction in the plasma PPi concentration and reduced PPi/Pi ratio. As a consequence, extensive aberrant mineralization affecting the arterial vasculature, a number of internal organs, and the dermal sheath of vibrissae, a progressive biomarker of the ectopic mineralization process, was demonstrated by a combination of micro computed tomography, histopathology with calcium-specific stains, and direct chemical assay of calcium. Comparison of the asj and asj-2J mice demonstrated that the latter ones, particularly when placed on an acceleration diet high in phosphate and low in magnesium, had more extensive mineralization. Thus, the asj-2J mouse serves as a novel model for GACI, a currently intractable disorder.

  8. Glutamate-system defects behind psychiatric manifestations in a familial hemiplegic migraine type 2 disease-mutation mouse model

    DEFF Research Database (Denmark)

    Bøttger, Pernille; Glerup, Simon; Gesslein, Bodil

    2016-01-01

    )) phenocopy several FHM2-relevant disease traits e.g., by mimicking mood depression and OCD. In vitro studies showed impaired glutamate uptake in hippocampal mixed astrocyte-neuron cultures from α2(G301R/G301R) E17 embryonic mice, and moreover, induction of cortical spreading depression (CSD) resulted......Migraine is a complex brain disorder, and understanding the complexity of this prevalent disease could improve quality of life for millions of people. Familial Hemiplegic Migraine type 2 (FHM2) is a subtype of migraine with aura and co-morbidities like epilepsy/seizures, cognitive impairments...... and psychiatric manifestations, such as obsessive-compulsive disorder (OCD). FHM2 disease-mutations locate to the ATP1A2 gene encoding the astrocyte-located α2-isoform of the sodium-potassium pump (α2Na(+)/K(+)-ATPase). We show that knock-in mice heterozygous for the FHM2-associated G301R-mutation (α2(+/G301R...

  9. Correction of compressor critical speed condition through fluid-film bearing optimization

    International Nuclear Information System (INIS)

    Spencer, J.W.; Obeid, V.E.

    1985-01-01

    A critical speed condition for an overhung centrifugal compressor was corrected through a relatively minor bearing modification. The resonant condition was evaluated analytically through rotor dynamic analyses (stability and forced response) which included fluid film bearing characterization and rotor model generation (experimentally evaluated by model analysis). The importance of adequate specification, inspection, and analytical characterization, of fluid film bearings are discussed. The effects of unbalance on the stability of plain journal bearings are also commented upon. 1 ref., 6 figs

  10. Bearing problems’ effects on the dynamic performance of pumping stations

    Directory of Open Access Journals (Sweden)

    Mostafa A. Abu-Zeid

    2013-09-01

    Pumping stations use large number of bearings with different types and applications. These bearings have a clear effect on the performance and efficiency of the pumps. Pump bearings in the arid regions are greatly affected by temperature, water quality, lubricants, and maintenance operations. This research focuses on analysis of damaged rolling element bearings of pumping system. The objective of the research is to enhance and control dynamic performance of pumping stations by avoiding damage and failure of bearings. The research proves that damaged bearings generate periodic, non-periodic, and transient forces causing high amplitude of vibration at high frequencies and increasing energy consumption. Bearing faults increase vibration level 85%, where power consumption increases 14% and pump efficiency decreases 18%. It is very important to take care of bearings during installation, alignment, balancing, and maintenance to assure safe and efficient pump operation for long period. As pump efficiency decreases, water power decreases and/or consumed power increases affecting water distribution and management system. Bearing faults break pumping system for long period affecting irrigation system. Optimum operation of pumping stations helps to save and manage water requirement for development and extension projects in arid regions. The measurements are performed on full scale model in the field, which proves reliable results on similar pumping stations.

  11. Targeting Faulty Bearings for an Ocean Turbine Dynamometer

    Directory of Open Access Journals (Sweden)

    David J. Vendittis

    2013-01-01

    Full Text Available A real-time, vibrations-based condition monitoring method used to detect, localize, and identify a faulty bearing in an ocean turbine electric motor is presented in this paper. The electric motor is installed in a dynamometer emulating the functions of the actual ocean turbine. High frequency modal analysis and power trending are combined to assess the operational health of the dynamometer’s bearings across an array of accelerometers. Once a defect has been detected, envelope analysis is used to identify the exact bearing containing the defect. After a brief background on bearing fault detection, this paper introduces a simplified mathematical model of the bearing fault, followed with the signal processing approach used to detect, locate, and identify the fault. In the results section, effectiveness of the methods of bearing fault detection presented in this paper is demonstrated through processing data collected, first, from a controlled lathe setup and, second, from the dynamometer. By mounting a bearing containing a defect punched into its inner raceway to a lathe and placing an array of accelerometers along the length of lathe, the bearing fault is clearly detected, localized, and identified as an inner raceway defect. Through retroactively trending the data leading to the near-failure of one of the electric motors in the dynamometer, the authors identified a positive trend in energy levels for a specific frequency band present across the array of accelerometers and identify two bearings as possible sources of the fault.

  12. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    Energy Technology Data Exchange (ETDEWEB)

    Andoh, T. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Sudo, T. [Section of Translational Research, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fujita, I.; Imabori, M. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Moritake, H. [Department of Pediatrics, Miyazaki University, Kiyotake 889-1692 (Japan); Sugimoto, T. [Department of Pediatrics, Saiseikai Shigaken Hospital, Ritto 520-3046 (Japan); Sakuma, Y. [Department of Pathology, Hyogo Cancer Center, Akashi 673-0021 (Japan); Takeuchi, T. [Department of Pathology, Kochi University, Nangoku 783-8505 (Japan); Kawabata, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Kirihata, M. [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai 599-8531 (Japan); Akisue, T. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Yayama, K. [Laboratory of Cardiovascular Pharmacology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Kurosaka, M. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Miyatake, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Fukumori, Y. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Ichikawa, H., E-mail: ichikawa@pharm.kobegakuin.ac.jp [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan)

    2011-12-15

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of {sup 10}B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  13. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    International Nuclear Information System (INIS)

    Andoh, T.; Fujimoto, T.; Sudo, T.; Fujita, I.; Imabori, M.; Moritake, H.; Sugimoto, T.; Sakuma, Y.; Takeuchi, T.; Kawabata, S.; Kirihata, M.; Akisue, T.; Yayama, K.; Kurosaka, M.; Miyatake, S.; Fukumori, Y.; Ichikawa, H.

    2011-01-01

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of 10 B (45–74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  14. Analysis of a Thrust Bearing with Flexible Pads and Flexible Supports

    DEFF Research Database (Denmark)

    Klit, Peder; Thomsen, Kim

    2007-01-01

    A theoretical analysis of a hydrodynamic thrust bearing is presented. The bearing investigated is used in an ndustrial product. The lubricant is water, but the results are valid also for other lubricants.At first the results from a 1-dimensional model for the fluid film forces and the associated...... deformation of the bearing geometry is presented. This model enlightens the influence of pad flexibility and support location and flexibility. Subsequently results from a 2-dimensional model of the bearing is presented. The model is used to carry out an optimization of the bearing design, and the obtained...

  15. Computational design of rolling bearings

    CERN Document Server

    Nguyen-Schäfer, Hung

    2016-01-01

    This book comprehensively presents the computational design of rolling bearings dealing with many interdisciplinary difficult working fields. They encompass elastohydrodynamics (EHD), Hertzian contact theory, oil-film thickness in elastohydrodynamic lubrication (EHL), bearing dynamics, tribology of surface textures, fatigue failure mechanisms, fatigue lifetimes of rolling bearings and lubricating greases, Weibull distribution, rotor balancing, and airborne noises (NVH) in the rolling bearings. Furthermore, the readers are provided with hands-on essential formulas based on the up-to-date DIN ISO norms and helpful examples for computational design of rolling bearings. The topics are intended for undergraduate and graduate students in mechanical and material engineering, research scientists, and practicing engineers who want to understand the interactions between these working fields and to know how to design the rolling bearings for automotive industry and many other industries.

  16. On the Design of Tilting-Pad Thrust Bearings

    DEFF Research Database (Denmark)

    Heinrichson, Niels

    2007-01-01

    Pockets are often machined in the surfaces of tilting-pad thrust bearings to allow for hydrostatic jacking in the start-up phase. Pockets and other recesses in the surfaces of bearing pads influence the pressure distribution and thereby the position of the pivot resulting in the most advantageous...... friction and a small pressure build-up. As in parallel-step bearings the recesses may also have a depth of the same order of magnitude as the oil film thickness. Such recesses are characterized by a strong pressure build-up caused by the reduction of the flow area at the end of the recess. Numerical models...... based on the Reynolds equation are used. They include the effects of variations of viscosity with temperature and the deformation of the bearing pads due to pressure and thermal gradients. The models are validated using measurements. Tilting-pad bearings of standard design are studied and the influences...

  17. Characterization of New Transgenic Mouse Models for Two Charcot-Marie-Tooth-Causing HspB1 Mutations using the Rosa26 Locus.

    Science.gov (United States)

    Bouhy, Delphine; Geuens, Thomas; De Winter, Vicky; Almeida-Souza, Leonardo; Katona, Istvan; Weis, Joachim; Hochepied, Tino; Goossens, Steven; Haigh, Jody J; Janssens, Sophie; Timmerman, Vincent

    2016-05-27

    Charcot-Marie-Tooth (CMT) and associated neuropathies, the most common inherited diseases of the peripheral nervous system, remain so far incurable. Three existing murine models of Charcot-Marie-Tooth type 2F (CMT2F) and/or distal hereditary motor neuropathy type IIb (dHMNIIb), caused by mutations in the small heat shock protein B1 gene (HSPB1/HSP27), partially recapitulate the hallmarks of peripheral neuropathy. Because these models overexpress the HSPB1 mutant proteins they differ from the patients' situation. To overcome the possible bias induced by overexpression, we generated and characterized a transgenic model in which the wild type or mutant HSPB1 protein was expressed at a moderate, more physiologically relevant level. We generated a new transgenic mouse model in which a human wild type (hHSPB1WT) or mutant (hHSPB1R127W; hHSPB1P182L) HSPB1 transgene was integrated in the mouse ROSA26 locus. The motor and sensory functions of the mice was assessed at 3, 6, 9, 12 and 18 month. However, the mice expressing the mutant hHSPB1 do not develop motor or sensory deficits and do not show any sign of axonal degeneration, even at late age. Quantitative PCR analyses reveal contrasting tissue-specific expression pattern for the endogenous mouse and exogenous human HSPB1 and show that the ratio of human HSPB1 to the endogenous mouse HspB1 is lower in the sciatic nerve and spinal cord compared to the brain. These results suggest that expressing the transgene at a physiological level using the ROSA26 locus may not be sufficient to model inherited peripheral neuropathies caused by mutation in HSPB1.

  18. Improvement of bearing support lubrication

    Directory of Open Access Journals (Sweden)

    Shehovtseva E. V.

    2016-12-01

    Full Text Available Gas turbine engine bearing supports is an important part in providing product efficiency of general and special-purpose engineering industry. Attempts are being made to increase efficiency of bearing support. Such attempts are caused by the modern tendency of the development of engineering striving for compact machines and units possessing increased reliability and durability. Researches on finding discrepancies in operation of support for this purpose have been executed. The reasons of occurrence the fatigue crumbling on external bearing races at different stages development of working surface damage have been investigated. The basic constructions of support of shaft for the aviation gas turbine engine and methods of their lubrication have been considered. Shortcomings of existing methods of lubrication of bearing supports have been marked. The upgraded construction of the module of gas turbine bearing shaft, which allows to improve conditions of lubrication and bearing cooling as a result of a uniform oil feed to the contact zones of outside bearing race and rolling elements and forced oil removal from contact zones of inside bearing race and rolling elements has been suggested. The task of improving conditions of lubrication supply to an internal holder of the bearing has been solved. The developed design allows applying unconventional methods of lubrication and cooling of a bearing support. Thus it is recommended to use process of regulation of a microrough on working surfaces bearing support during grinding-in. It will allow to improve a stage grinding-in and to increase reliability and durability of bearing support.

  19. The risk of extinction - the mutational meltdown or the overpopulation.

    Science.gov (United States)

    Malarz, Krzysztof

    2007-04-01

    The phase diagrams survival-extinction for the Penna model with parameters: (mutations rate)-(birth rate), (mutation rate)-(harmful mutations threshold), (harmful mutation threshold)-(minimal reproduction age) are presented. The extinction phase may be caused by either mutational meltdown or overpopulation. When the Verhulst factor is responsible for removing only newly born babies and does not act on adults the overpopulation is avoided and only genetic factors may lead to species extinction.

  20. The risk of extinction - the mutational meltdown or the overpopulation

    OpenAIRE

    Malarz, K.

    2006-01-01

    The phase diagrams survival-extinction for the Penna model with parameters: (mutations rate)-(birth rate), (mutation rate)-(harmful mutations threshold), (harmful mutation threshold)-(minimal reproduction age) are presented. The extinction phase may be caused by either mutational meltdown or overpopulation. When the Verhulst factor is responsible for removing only newly born babies and does not act on adults the overpopulation is avoided and only genetic factors may lead to species extinction.

  1. Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

    Science.gov (United States)

    McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Castillo, Alesha B; Kennedy, Oran; Condon, Keith W; Auger, Janene; Black, Hal L; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2009-12-01

    Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis.

  2. Hydrostatic and hybrid bearing design

    CERN Document Server

    Rowe, W B

    1983-01-01

    Hydrostatic and Hybrid Bearing Design is a 15-chapter book that focuses on the bearing design and testing. This book first describes the application of hydrostatic bearings, as well as the device pressure, flow, force, power, and temperature. Subsequent chapters discuss the load and flow rate of thrust pads; circuit design, flow control, load, and stiffness; and the basis of the design procedures and selection of tolerances. The specific types of bearings, their design, dynamics, and experimental methods and testing are also shown. This book will be very valuable to students of engineering des

  3. Sub-basalt Imaging of Hydrocarbon-Bearing Mesozoic Sediments Using Ray-Trace Inversion of First-Arrival Seismic Data and Elastic Finite-Difference Full-Wave Modeling Along Sinor-Valod Profile of Deccan Syneclise, India

    Science.gov (United States)

    Talukdar, Karabi; Behera, Laxmidhar

    2018-03-01

    Imaging below the basalt for hydrocarbon exploration is a global problem because of poor penetration and significant loss of seismic energy due to scattering, attenuation, absorption and mode-conversion when the seismic waves encounter a highly heterogeneous and rugose basalt layer. The conventional (short offset) seismic data acquisition, processing and modeling techniques adopted by the oil industry generally fails to image hydrocarbon-bearing sub-trappean Mesozoic sediments hidden below the basalt and is considered as a serious problem for hydrocarbon exploration in the world. To overcome this difficulty of sub-basalt imaging, we have generated dense synthetic seismic data with the help of elastic finite-difference full-wave modeling using staggered-grid scheme for the model derived from ray-trace inversion using sparse wide-angle seismic data acquired along Sinor-Valod profile in the Deccan Volcanic Province of India. The full-wave synthetic seismic data generated have been processed and imaged using conventional seismic data processing technique with Kirchhoff pre-stack time and depth migrations. The seismic image obtained correlates with all the structural features of the model obtained through ray-trace inversion of wide-angle seismic data, validating the effectiveness of robust elastic finite-difference full-wave modeling approach for imaging below thick basalts. Using the full-wave modeling also allows us to decipher small-scale heterogeneities imposed in the model as a measure of the rugose basalt interfaces, which could not be dealt with ray-trace inversion. Furthermore, we were able to accurately image thin low-velocity hydrocarbon-bearing Mesozoic sediments sandwiched between and hidden below two thick sequences of high-velocity basalt layers lying above the basement.

  4. Autosizing Control Panel for Needle Bearing

    OpenAIRE

    Prof.A.R.Wadhekar,; Ms Jyoti R. Rajput

    2016-01-01

    A needle roller bearing is a bearing which uses small cylindrical rollers. Bearings are used to reduce friction of any rotating surface. Needle bearings have a large surface in contact with the bearing outer surfaces as compared to ball bearings. There is less added clearance(Diameter of the shaft and the diameter of the bearing are different) so they are much compact. The structure consists of a needle cage which contains the needle rollersthemselves and an outer race (The housin...

  5. Spastic paraplegia mutation N256S in the neuronal microtubule motor KIF5A disrupts axonal transport in a Drosophila HSP model.

    Directory of Open Access Journals (Sweden)

    Petra Füger

    Full Text Available Hereditary spastic paraplegias (HSPs comprise a group of genetically heterogeneous neurodegenerative disorders characterized by spastic weakness of the lower extremities. We have generated a Drosophila model for HSP type 10 (SPG10, caused by mutations in KIF5A. KIF5A encodes the heavy chain of kinesin-1, a neuronal microtubule motor. Our results imply that SPG10 is not caused by haploinsufficiency but by the loss of endogenous kinesin-1 function due to a selective dominant-negative action of mutant KIF5A on kinesin-1 complexes. We have not found any evidence for an additional, more generalized toxicity of mutant Kinesin heavy chain (Khc or the affected kinesin-1 complexes. Ectopic expression of Drosophila Khc carrying a human SPG10-associated mutation (N256S is sufficient to disturb axonal transport and