WorldWideScience

Sample records for numerous critical roles

  1. Numerical Study of Critical Role of Rock Heterogeneity in Hydraulic Fracture Propagation

    Energy Technology Data Exchange (ETDEWEB)

    J. Zhou; H. Huang; M. Deo

    2016-03-01

    Log and seismic data indicate that most shale formations have strong heterogeneity. Conventional analytical and semi-analytical fracture models are not enough to simulate the complex fracture propagation in these highly heterogeneous formation. Without considering the intrinsic heterogeneity, predicted morphology of hydraulic fracture may be biased and misleading in optimizing the completion strategy. In this paper, a fully coupling fluid flow and geomechanics hydraulic fracture simulator based on dual-lattice Discrete Element Method (DEM) is used to predict the hydraulic fracture propagation in heterogeneous reservoir. The heterogeneity of rock is simulated by assigning different material force constant and critical strain to different particles and is adjusted by conditioning to the measured data and observed geological features. Based on proposed model, the effects of heterogeneity at different scale on micromechanical behavior and induced macroscopic fractures are examined. From the numerical results, the microcrack will be more inclined to form at the grain weaker interface. The conventional simulator with homogeneous assumption is not applicable for highly heterogeneous shale formation.

  2. Numerical Simulation of the Kinetic Critical Nucleus

    OpenAIRE

    Sanada, Masaaki; Nishioka, Kazumi; Okada, Masahumi; Maksimov, Igor, L.

    1997-01-01

    Our main interest is to see whether the number density indicates a peak at the kinetically stable critical nucleus due to its kinetical stability. We have numerically calculated the time evolution of the number densities of clusters in the case of water vapor nucleation. We employ the condition in which the difference between the size of the thermodynamic crtitical nucleus and that of the kinetic one is appreciable. The results show that the peak does not appear in the number densities of clu...

  3. Numerical Study on Critical Wedge Angle of Cellular Detonation Reflections

    International Nuclear Information System (INIS)

    Gang, Wang; Kai-Xin, Liu; De-Liang, Zhang

    2010-01-01

    The critical wedge angle (CWA) for the transition from regular reflection (RR) to Mach reflection (MR) of a cellular detonation wave is studied numerically by an improved space-time conservation element and solution element method together with a two-step chemical reaction model. The accuracy of that numerical way is verified by simulating cellular detonation reflections at a 19.3° wedge. The planar and cellular detonation reflections over 45°–55° wedges are also simulated. When the cellular detonation wave is over a 50° wedge, numerical results show a new phenomenon that RR and MR occur alternately. The transition process between RR and MR is investigated with the local pressure contours. Numerical analysis shows that the cellular structure is the essential reason for the new phenomenon and the CWA of detonation reflection is not a certain angle but an angle range. (fundamental areas of phenomenology(including applications))

  4. A note on numerical solution to the problem of criticality

    International Nuclear Information System (INIS)

    Kyncl, J.

    2002-01-01

    The contribution deals with numerical solution to the problem of criticality for neutron transport equation by the external source iteration method. Especially, the speed of convergence is examined. It is shown that if neutron absorption in the medium considered is high and if the space region occupied by the medium is large then a slow convergence of the iterations can be expected. This expectation is confirmed by results to CB4 benchmark obtained by MCNP code. Besides the results presented some questions concerning applications of them to criticality calculations are pointed out (Author)

  5. Numerical solutions to critical problem of reflected cylindrical reactor

    International Nuclear Information System (INIS)

    Horie, Junnosuke

    1977-01-01

    The multi-region critical problem can be transformed into an eigenvalue problem in the classical sense by using the method of Kuscer and Corngold and of Wing. This transformation is applied to derive a variational formulation for a reflected reactor. An approximate critical value of the multiplying factor is determined by maximizing the Rayleigh quotient for radially and totally reflected cylindrical reactors. It is shown that this approximate critical value is an upper bound of the true critical value. From the facts that the operator is self-adjoint and the eigenfunction is positive, an expression is derived for the upper and lower bounds of the true eigenvalue, by making use of the approximate distribution. The difference of the upper and lower bounds is an uncertainty of the presumption of the true critical value. It is found that we can compute the bounds to any required precision. The narrow bounds are calculated for two radially and one totally reflected cylindrical reactors. (auth.)

  6. Numerical analysis of critical two-phase flow in a convergent-divergent nozzle

    International Nuclear Information System (INIS)

    Romstedt, P.; Werner, W.

    1985-01-01

    The numerical calculation of critical two-phase flow in a convergent-divergent nozzle is complicated by a singularity of the fluid flow equations at the unknown critical point. This paper describes a method which is able to calculate critical state and its location without any additional assumptions. The critical state is identified by its mathematical properties: characteristics and solvability of linear systems with singular matrix. Because the numerically evaluable mathematical properties are only necessary conditions for the existence of critical flow, some physical ''compatibility-criteria'' (flow velocity equals two-phase sonic velocity, critical flow is independent of downstream flow state variations) are used as a substitute for mathematically sufficient conditions. Numerical results are shown for the critical flow in a LOBI nozzle; the two-phase flow is described by a model with equal phase velocities and thermodynamic non-equilibrium

  7. On the theories, techniques, and computer codes used in numerical reactor criticality and burnup calculations

    International Nuclear Information System (INIS)

    El-Osery, I.A.

    1981-01-01

    The purpose of this paper is to discuss the theories, techniques and computer codes that are frequently used in numerical reactor criticality and burnup calculations. It is a part of an integrated nuclear reactor calculation scheme conducted by the Reactors Department, Inshas Nuclear Research Centre. The crude part in numerical reactor criticality and burnup calculations includes the determination of neutron flux distribution which can be obtained in principle as a solution of Boltzmann transport equation. Numerical methods used for solving transport equations are discussed. Emphasis are made on numerical techniques based on multigroup diffusion theory. These numerical techniques include nodal, modal, and finite difference ones. The most commonly known computer codes utilizing these techniques are reviewed. Some of the main computer codes that have been already developed at the Reactors Department and related to numerical reactor criticality and burnup calculations have been presented

  8. Numerical simulation of trans-critical carbon dioxide (R744) flow through short tube orifices

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Valladares, O. [Centro de Investigacion en Energia de la Universidad Nacional Autonoma de Mexico, Privada Xochicalco S/N, Apdo. Postal 34, 62580 Temixco, Morelos (Mexico)

    2006-02-01

    A detailed one-dimensional numerical simulation of the fluid-dynamic behaviour of short tube orifices expansion devices working with trans-critical carbon dioxide (CO{sub 2} or R744) has been developed. The discretized governing equations are coupled using an implicit step by step method. A special treatment has been implemented in order to consider transitions (subcooled liquid region and equilibrium two-phase region). The numerical model allows analysis of aspects such as geometry, different working conditions, critical or non-critical flow conditions, etc. Comparison of the numerical simulation with experimental data presented in the technical literature will be shown in the present article. (author)

  9. Numerical difficulties to obtain 3-d critical exponents from platonic solids

    International Nuclear Information System (INIS)

    Alcaraz, F.C.; Herrmann, H.J.

    1985-01-01

    The possibility to extract critical exponents of 3-d systems exploring the mass gap amplitudes of platonic solids is tested. For the Ising model the proposed method does not work for numerical reasons. (Author) [pt

  10. Experimental and numerical investigations of resonant acoustic waves in near-critical carbon dioxide.

    Science.gov (United States)

    Hasan, Nusair; Farouk, Bakhtier

    2015-10-01

    Flow and transport induced by resonant acoustic waves in a near-critical fluid filled cylindrical enclosure is investigated both experimentally and numerically. Supercritical carbon dioxide (near the critical or the pseudo-critical states) in a confined resonator is subjected to acoustic field created by an electro-mechanical acoustic transducer and the induced pressure waves are measured by a fast response pressure field microphone. The frequency of the acoustic transducer is chosen such that the lowest acoustic mode propagates along the enclosure. For numerical simulations, a real-fluid computational fluid dynamics model representing the thermo-physical and transport properties of the supercritical fluid is considered. The simulated acoustic field in the resonator is compared with measurements. The formation of acoustic streaming structures in the highly compressible medium is revealed by time-averaging the numerical solutions over a given period. Due to diverging thermo-physical properties of supercritical fluid near the critical point, large scale oscillations are generated even for small sound field intensity. The strength of the acoustic wave field is found to be in direct relation with the thermodynamic state of the fluid. The effects of near-critical property variations and the operating pressure on the formation process of the streaming structures are also investigated. Irregular streaming patterns with significantly higher streaming velocities are observed for near-pseudo-critical states at operating pressures close to the critical pressure. However, these structures quickly re-orient to the typical Rayleigh streaming patterns with the increase operating pressure.

  11. Experimental and Numerical Analysis of S-CO2 Critical Flow for SFR Recovery System Design

    International Nuclear Information System (INIS)

    Kim, Min Seok; Jung, Hwa-Young; Ahn, Yoonhan; Lee, Jekyoung; Lee, Jeong Ik

    2016-01-01

    This paper presents both numerical and experimental studies of the critical flow of S-CO 2 while special attention is given to the turbo-machinery seal design. A computational critical flow model is described first. The experiments were conducted to validate the critical flow model. Various conditions have been tested to study the flow characteristic and provide validation data for the model. The comparison of numerical and experimental results of S-CO 2 critical flow will be presented. In order to eliminate SWR, a concept of coupling the Supercritical CO 2 (S-CO 2 ) cycle with SFR has been proposed. It is known that for a closed system controlling the inventory is important for stable operation and achieving high efficiency. Since the S-CO 2 power cycle is a highly pressurized system, certain amount of leakage flow is inevitable in the rotating turbo-machinery via seals. To simulate the CO 2 leak flow in a turbo-machinery with higher accuracy in the future, the real gas effect and friction factor will be considered for the CO 2 critical flow model. Moreover, experimentally obtained temperature data were somewhat different from the numerically obtained temperature due to the insufficient insulation and large thermal inertia of the CO 2 critical flow facility. Insulation in connecting pipes and the low-pressure tank will be added and additional tests will be conducted

  12. The Role of Critical Thinking in Science Education

    Science.gov (United States)

    Santos, Luis Fernando

    2017-01-01

    This review aims to respond various questions regarding the role of Critical Thinking in Science Education from aspects concerning the importance or relevance of critical thinking in science education, the situation in the classroom and curriculum, and the conception of critical thinking and fostering in science education. This review is specially…

  13. Numerical verification of the theory of coupled reactors for a deuterium critical assembly using MCNP5

    International Nuclear Information System (INIS)

    Hussein, M.S.; Bonin, H.W.; Lewis, B.J.

    2013-01-01

    The theory of multipoint coupled reactors developed by multi-group transport is verified by using the probabilistic transport code MCNP5. The verification was performed by calculating the multiplication factors (or criticality factors) and coupling coefficients for a two-region test reactor known as Deuterium Critical Assembly, (DCA). The variations of the criticality factors and the coupling coefficients were investigated by changing of the water levels in the inner and outer cores. The numerical results of the model developed with MCNP5 code were validated and verified against published results and the mathematical model based on coupled reactor theory. (author)

  14. Numerical verification of the theory of coupled reactors for a deuterium critical assembly using MCNP5

    Energy Technology Data Exchange (ETDEWEB)

    Hussein, M.S.; Bonin, H.W.; Lewis, B.J., E-mail: mohamed.hussein@rmc.ca, E-mail: bonin-h@rmc.ca, E-mail: lewis-b@rmc.ca [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada)

    2013-07-01

    The theory of multipoint coupled reactors developed by multi-group transport is verified by using the probabilistic transport code MCNP5. The verification was performed by calculating the multiplication factors (or criticality factors) and coupling coefficients for a two-region test reactor known as Deuterium Critical Assembly, (DCA). The variations of the criticality factors and the coupling coefficients were investigated by changing of the water levels in the inner and outer cores. The numerical results of the model developed with MCNP5 code were validated and verified against published results and the mathematical model based on coupled reactor theory. (author)

  15. Stability in shifting sands: contemporary leadership roles in critical care.

    Science.gov (United States)

    Endacott, R; Boulanger, C; Chamberlain, W; Hendry, J; Ryan, H; Chaboyer, W

    2008-10-01

    Contemporary nursing leadership roles in critical care are a reflection of the changing environment in which critical care is provided. In the UK, critical care nursing faces challenges in the form of: reduced number and seniority of medical staff cover for acute wards; mandated responsibility for management of patients outside of critical care units, without corresponding responsibility for managing staff; increased public and political awareness of deficits in critical care; increased use of Assistant Practitioners; and emphasis on longer-term outcomes from intensive care. New leadership roles have met these challenges head on with two main foci: patient management across the acute/critical care interface and hospital wide policies and practice. The leadership roles examined in this paper highlight three underpinning goals: improved quality and safety of patient care; improved communication between professionals; and empowerment of junior nurses and doctors. There has been considerable investment in strategic leadership roles for critical care nursing; evidence is developing of the return on this investment for patient and service outcomes. Consideration must now be given to the preparation, mentorship and development of leadership roles for the next generation of nurse leaders.

  16. The role of visualisation in developing critical thinking in mathematics

    African Journals Online (AJOL)

    Research has been conducted on the role and importance of visualisation in many fields, including psychology, but very little has been done to extend its role to mathematics education in particular. Furthermore, much research has been done on the importance of critical thinking. However, to date not much has been done ...

  17. Foundations of children's numerical and mathematical skills: the roles of symbolic and nonsymbolic representations of numerical magnitude.

    Science.gov (United States)

    Lyons, Ian M; Ansari, Daniel

    2015-01-01

    Numerical and mathematical skills are critical predictors of academic success. The last three decades have seen a substantial growth in our understanding of how the human mind and brain represent and process numbers. In particular, research has shown that we share with animals the ability to represent numerical magnitude (the total number of items in a set) and that preverbal infants can process numerical magnitude. Further research has shown that similar processing signatures characterize numerical magnitude processing across species and developmental time. These findings suggest that an approximate system for nonsymbolic (e.g., dot arrays) numerical magnitude representation serves as the basis for the acquisition of cultural, symbolic (e.g., Arabic numerals) representations of numerical magnitude. This chapter explores this hypothesis by reviewing studies that have examined the relation between individual differences in nonsymbolic numerical magnitude processing and symbolic math abilities (e.g., arithmetic). Furthermore, we examine the extent to which the available literature provides strong evidence for a link between symbolic and nonsymbolic representations of numerical magnitude at the behavioral and neural levels of analysis. We conclude that claims that symbolic number abilities are grounded in the approximate system for the nonsymbolic representation of numerical magnitude are not strongly supported by the available evidence. Alternative models and future research directions are discussed. © 2015 Elsevier Inc. All rights reserved.

  18. Healthcare reform: the role of coordinated critical care.

    Science.gov (United States)

    Cerra, F B

    1993-03-01

    To evaluate and editorialize the evolving role of the discipline of critical care as a healthcare delivery system in the process of healthcare reform. The sources included material from the Federal Office of Management and Budget, Health Care Financing Review, President Bush's Office, Association of American Medical Colleges, and publications of the Society of Critical Care Medicine. Data were selected that the author felt was relevant to the healthcare reform process and its implications for the discipline of critical care. The data were extracted by the author to illustrate the forces behind healthcare reform, the implications for the practice of critical care, and role of critical care as a coordinated (managed) care system in the process of healthcare reform. Healthcare reform has been initiated because of a number of considerations that arise in evaluating the current healthcare delivery system: access, financing, cost, dissatisfactions with the mechanisms of delivery, and political issues. The reform process will occur with or without the involvement of critical care practitioners. Reforms may greatly alter the delivery of critical care services, education, training, and research in critical care. Critical care has evolved into a healthcare delivery system that provides services to patients who need and request them and provides these services in a coordinated (managed) care model. Critical care practitioners must become involved in the healthcare reform process, and critical care services that are effective must be preserved, as must the education, training, and research programs. Critical care as a healthcare delivery system utilizing a coordinated (managed) care model has the potential to provide services to all patients who need them and to deliver them in a manner that is cost effective and recognized as providing added value.

  19. Numerical solutions to the critical state in a magnet-high temperature superconductor interaction

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz-Alonso, D; Coombs, T A; Campbell, A M [Cambridge University Engineering Department, Trumpington Street, Cambridge CB2 1PZ (United Kingdom)

    2005-02-01

    This paper presents an algorithm to simulate the electromagnetic behaviour of devices containing high temperature superconductors in axially symmetric problems. The numerical method is built within the finite element method. The electromagnetic properties of HTSCs are described through the critical-state model. Measurements of the axial force between a permanent magnet and a melt-textured YBCO puck are obtained in order to validate the method. This simple system is modelled so that the proposed method obtains the current distribution and electromagnetic fields in the HTSC. The forces in the interaction between the magnet and the HTSC puck can then be calculated. A comparison between experimental and simulation results shows good matching. The simplification of using the critical-state model and ignoring flux creep in this type of configuration is also explored.

  20. Maximizing Team Performance: The Critical Role of the Nurse Leader.

    Science.gov (United States)

    Manges, Kirstin; Scott-Cawiezell, Jill; Ward, Marcia M

    2017-01-01

    Facilitating team development is challenging, yet critical for ongoing improvement across healthcare settings. The purpose of this exemplary case study is to examine the role of nurse leaders in facilitating the development of a high-performing Change Team in implementing a patient safety initiative (TeamSTEPPs) using the Tuckman Model of Group Development as a guiding framework. The case study is the synthesis of 2.5 years of critical access hospital key informant interviews (n = 50). Critical juncture points related to team development and key nurse leader actions are analyzed, suggesting that nurse leaders are essential to maximize clinical teams' performance. © 2016 Wiley Periodicals, Inc.

  1. Numerical versus analytical Ic(H) patterns in Josephson junctions with periodically alternating critical current density

    International Nuclear Information System (INIS)

    Lazarides, N

    2004-01-01

    An analytical expression for the magnetic-field-dependent critical current I c (H) of Josephson junctions with periodically alternating critical current density J c (x) is derived within the uniform field approximation. Comparison with numerically calculated I c (H) patterns for junctions with identical, thick, periodically arranged defects with the corresponding analytical expression reveals fair agreement for a wide range of parameters, due to increased characteristic length. Based on qualitative arguments, we give the dependence of the new characteristic length on the geometrical parameters of the junction, which is in agreement with self-consistent calculations with the static sine-Gordon equation. The analytical expression captures the observed qualitative features of the I c (H) patterns, while it is practically exact for short junctions or high fields. It also produces the shift of the major peak from the zero-field position of the standard Fraunhofer pattern to another position related to the periodicity of the critical current density in φ-junctions

  2. Experimental and numerical study of influence of ferromagnetic cover on critical current of BiSCCO-2223/Ag tape superconductor

    International Nuclear Information System (INIS)

    Vojenciak, M; Souc, J; Goemoery, F

    2009-01-01

    Samples of commercially available BiSCCO-2223/Ag tape have been partially covered by the ferromagnetic material. Improvement of the self-field critical current up to 15 % has been achieved by this procedure. A critical current of such tape strongly depends on geometric and magnetic properties of both, the superconducting tape as well as the ferromagnetic cover. Numerical simulations, based on the critical state model using commercial finite element method (FEM) code, have been performed. Properties of superconductor are characterized by anisotropic dependence of the critical current density on magnetic field as well as detail geometry of filaments. The ferromagnetic material is characterized by nonlinear magnetization curve. Nonlinear dependences of the critical current on selected parameters are shown in this work. Optimization of the cover parameters using these curves has been made. Samples with various parameters have been manufactured for the confirmation of numerical simulations results. Experimental results are in good qualitative agreement with results obtained by numerical simulations.

  3. Developing group investigation-based book on numerical analysis to increase critical thinking student’s ability

    Science.gov (United States)

    Maharani, S.; Suprapto, E.

    2018-03-01

    Critical thinking is very important in Mathematics; it can make student more understanding mathematics concept. Critical thinking is also needed in numerical analysis. The Numerical analysis's book is not yet including critical thinking in them. This research aims to develop group investigation-based book on numerical analysis to increase critical thinking student’s ability, to know the quality of the group investigation-based book on numerical analysis is valid, practical, and effective. The research method is Research and Development (R&D) with the subject are 30 student college department of Mathematics education at Universitas PGRI Madiun. The development model used is 4-D modified to 3-D until the stage development. The type of data used is descriptive qualitative data. Instruments used are sheets of validation, test, and questionnaire. Development results indicate that group investigation-based book on numerical analysis in the category of valid a value 84.25%. Students response to the books very positive, so group investigation-based book on numerical analysis category practical, i.e., 86.00%. The use of group investigation-based book on numerical analysis has been meeting the completeness criteria classical learning that is 84.32 %. Based on research result of this study concluded that group investigation-based book on numerical analysis is feasible because it meets the criteria valid, practical, and effective. So, the book can be used by every mathematics academician. The next research can be observed that book based group investigation in other subjects.

  4. Numerical investigation on critical heat flux and coolant volume required for transpiration cooling with phase change

    International Nuclear Information System (INIS)

    He, Fei; Wang, Jianhua

    2014-01-01

    Highlights: • Five states during the transpiration cooling are discussed. • A suit of applicable program is developed. • The variations of the thickness of two-phase region and the pressure are analyzed. • The relationship between heat flux and coolant mass flow rate is presented. • An approach is given to define the desired case of transpiration cooling. - Abstract: The mechanism of transpiration cooling with liquid phase change is numerically investigated to protect the thermal structure exposed to extremely high heat flux. According to the results of theoretical analysis, there is a lower critical and an upper critical external heat flux corresponding a certain coolant mass flow rate, between the two critical values, the phase change of liquid coolant occurs within porous structure. A strongly applicable self-edit program is developed to solve the states of fluid flow and heat transfer probably occurring during the phase change procedure. The distributions of temperature and saturation in these states are presented. The variations of the thickness of two-phase region and the pressure including capillary are analyzed, and capillary pressure is found to be the main factor causing pressure change. From the relationships between the external heat flux and coolant mass flow rate obtained at different cooling cases, an approach is given to estimate the maximal heat flux afforded and the minimal coolant consumption required by the desired case of transpiration cooling. Thus the pressure and coolant consumption required in a certain thermal circumstance can be determined, which are important in the practical application of transpiration cooling

  5. The role of similarity in updating numerical information in working memory: decomposing the numerical distance effect.

    Science.gov (United States)

    Lendínez, Cristina; Pelegrina, Santiago; Lechuga, M Teresa

    2014-01-01

    The present study investigates the process of updating representations in working memory (WM) and how similarity between the information involved influences this process. In WM updating tasks, the similarity in terms of numerical distance between the number to be substituted and the new one facilitates the updating process. We aimed to disentangle the possible effect of two dimensions of similarity that may contribute to this numerical effect: numerical distance itself and common digits shared between the numbers involved. Three experiments were conducted in which different ranges of distances and the coincidence between the digits of the two numbers involved in updating were manipulated. Results showed that the two dimensions of similarity had an effect on updating times. The greater the similarity between the information maintained in memory and the new information that substituted it, the faster the updating. This is consistent both with the idea of distributed representations based on features, and with a selective updating process based on a feature overwriting mechanism. Thus, updating in WM can be understood as a selective substitution process influenced by similarity in which only certain parts of the representation stored in memory are changed.

  6. Criticism in izibongo zamakhosi : The changing role of the modern ...

    African Journals Online (AJOL)

    The imbongi was free in the times of the really powerful Zulu kings to pass any criticism he saw fit within the ambit of the king's praises, in order to alert the king to his peoples' opinions as well as caution him on certain actions. Today the role of the imbongi is far more tenuous. In times gone by, this man not only played a ...

  7. Numerical

    Directory of Open Access Journals (Sweden)

    M. Boumaza

    2015-07-01

    Full Text Available Transient convection heat transfer is of fundamental interest in many industrial and environmental situations, as well as in electronic devices and security of energy systems. Transient fluid flow problems are among the more difficult to analyze and yet are very often encountered in modern day technology. The main objective of this research project is to carry out a theoretical and numerical analysis of transient convective heat transfer in vertical flows, when the thermal field is due to different kinds of variation, in time and space of some boundary conditions, such as wall temperature or wall heat flux. This is achieved by the development of a mathematical model and its resolution by suitable numerical methods, as well as performing various sensitivity analyses. These objectives are achieved through a theoretical investigation of the effects of wall and fluid axial conduction, physical properties and heat capacity of the pipe wall on the transient downward mixed convection in a circular duct experiencing a sudden change in the applied heat flux on the outside surface of a central zone.

  8. A critical role of hypocretin deficiency in pregnancy.

    Science.gov (United States)

    Bastianini, Stefano; Berteotti, Chiara; Lo Martire, Viviana; Silvani, Alessandro; Zoccoli, Giovanna

    2014-04-01

    Hypocretin/orexin peptides are known for their role in the control of the wake–sleep cycle and narcolepsy–cataplexy pathophysiology. Recent studies suggested that hypocretin peptides also have a role in pregnancy. We tested this hypothesis by conducting a retrospective analysis on pregnancy complications in two different mouse models of hypocretin deficiency. We recorded 85 pregnancies of mice lacking either hypocretin peptides (knockout) or hypocretin-releasing neurons (transgenic) and their wild-type controls. Pregnancy was associated with unexplained dam death before delivery in 3/15 pregnancies in knockout mice, and in 3/23 pregnancies in transgenic mice. No casualties occurred in wild-type pregnant dams (P hypocretin-deficient mice as a whole). Hypocretin deficiency did not impact either on litter size or the number of weaned pups per litter. These data provide preliminary evidence of a critical role of hypocretin deficiency in pregnancy.

  9. Critical thinking and the role of the clinical ultrasound tutor

    International Nuclear Information System (INIS)

    Edwards, Hazel

    2006-01-01

    As radiographers continue to extend their role and take on more procedures associated traditionally with radiologists, it is essential that their critical thinking abilities keep pace with the new practical skills they are learning. This is particularly important in ultrasound where student sonographers must master a number of new skills including the technical dexterity required to perform a scan, the ability to form and discard hypotheses when trying to interpret the image, and the communication of their findings as a written report. Interpreting the image and producing an accurate, appropriate report involves the higher level cognitive processes of analysis, synthesis and evaluation. In other words, the student sonographer must be able to think critically to become a successful practitioner. This paper attempts to define and discuss critical thinking, and considers a range of simple strategies that the clinical teacher of ultrasound can employ to help develop critical thinking skills in their students. These methods are appropriate for use not only by clinical teachers of ultrasound but for all teachers and mentors wishing to improve reasoning skills in their pupils

  10. Numerical simulation and experimental validation of internal heat exchanger influence on CO{sub 2} trans-critical cycle performance

    Energy Technology Data Exchange (ETDEWEB)

    Rigola, Joaquim; Ablanque, Nicolas; Perez-Segarra, Carlos D.; Oliva, Assensi [Centre Tecnologic de Transferencia de Calor (CTTC), Universitat Politecnica de Catalunya (UPC), ETSEIAT, C. Colom 11, 08222 Terrassa (Barcelona) (Spain)

    2010-06-15

    The present paper is a numerical and experimental comparative study of the whole vapour compression refrigerating cycle in general, and reciprocating compressors in particular, with the aim of showing the possibilities that CO{sub 2} offers for commercial refrigeration, considering a single-stage trans-critical cycle using semi-hermetic reciprocating compressors under small cooling capacity systems. The present work is focussed on the influence of using an internal heat exchanger (IHX) in order to improve the cycle performance under real working conditions. In order to validate the numerical results, an experimental unit specially designed and built to analyze trans-critical refrigerating equipments considering IHX has been built. Both numerical results and experimental data show reasonable good agreement, while the comparative global values conclude the improvement of cooling capacity and COP when IHX is considered in the CO{sub 2} trans-critical cycle. (author)

  11. Multiple attractors and critical parameters and how to find them numerically: the right, the wrong and the gambling way

    DEFF Research Database (Denmark)

    True, Hans

    2013-01-01

    In recent years, several authors have proposed easier numerical methods to find the critical speed in railway dynamical problems. Actually, the methods do function in some cases, but in most cases it is really a gamble. In this article, the methods are discussed and the pros and contras are comme......In recent years, several authors have proposed easier numerical methods to find the critical speed in railway dynamical problems. Actually, the methods do function in some cases, but in most cases it is really a gamble. In this article, the methods are discussed and the pros and contras...

  12. Critical role of bicarbonate and bicarbonate transporters in cardiac function

    OpenAIRE

    Wang, Hong-Sheng; Chen, Yamei; Vairamani, Kanimozhi; Shull, Gary E

    2014-01-01

    Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2O, either spontaneously or via the catalytic activity of carbonic anhydrase. It serves as a component of the major buffer system, thereby playing a critical role in pH homeostasis. Bicarbonate can also be utilized by a variety of ion transporters, often working in coupled systems, to transport other ions and organic substrates across cell membrane...

  13. Experimental and Numerical Analysis of S-CO{sub 2} Critical Flow for SFR Recovery System Design

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Seok; Jung, Hwa-Young; Ahn, Yoonhan; Lee, Jekyoung; Lee, Jeong Ik [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2016-05-15

    This paper presents both numerical and experimental studies of the critical flow of S-CO{sub 2} while special attention is given to the turbo-machinery seal design. A computational critical flow model is described first. The experiments were conducted to validate the critical flow model. Various conditions have been tested to study the flow characteristic and provide validation data for the model. The comparison of numerical and experimental results of S-CO{sub 2} critical flow will be presented. In order to eliminate SWR, a concept of coupling the Supercritical CO{sub 2} (S-CO{sub 2}) cycle with SFR has been proposed. It is known that for a closed system controlling the inventory is important for stable operation and achieving high efficiency. Since the S-CO{sub 2} power cycle is a highly pressurized system, certain amount of leakage flow is inevitable in the rotating turbo-machinery via seals. To simulate the CO{sub 2} leak flow in a turbo-machinery with higher accuracy in the future, the real gas effect and friction factor will be considered for the CO{sub 2} critical flow model. Moreover, experimentally obtained temperature data were somewhat different from the numerically obtained temperature due to the insufficient insulation and large thermal inertia of the CO{sub 2} critical flow facility. Insulation in connecting pipes and the low-pressure tank will be added and additional tests will be conducted.

  14. Universal role of correlation entropy in critical phenomena

    International Nuclear Information System (INIS)

    Gu Shijian; Sun Changpu; Lin Haiqing

    2008-01-01

    In statistical physics, if we divide successively an equilibrium system into two parts, we will face a situation that, to a certain length ξ, the physics of a subsystem is no longer the same as the original one. The extensive property of the thermal entropy S(A union B) = S(A) + S(B) is then violated. This observation motivates us to introduce a concept of correlation entropy between two points, as measured by the mutual information in information theory, to study the critical phenomena. A rigorous relation is established to display some drastic features of the non-vanishing correlation entropy of a subsystem formed by any two distant particles with long-range correlation. This relation actually indicates a universal role played by the correlation entropy for understanding the critical phenomena. We also verify these analytical studies in terms of two well-studied models for both the thermal and quantum phase transitions: the two-dimensional Ising model and the one-dimensional transverse-field Ising model. Therefore, the correlation entropy provides us with a new physical intuition of the critical phenomena from the point of view of information theory

  15. On multiple attractors and critical parameters and how to find them numerically: The right, the wrong and "the American way"

    DEFF Research Database (Denmark)

    True, Hans

    2011-01-01

    In recent years several authors have proposed, "easier" numerical methods' to find the critical speed in railway dynamical problems. Actually the methods do function in some cases, but in most cases it is really a gamble. In this presentation the methods will be discussed and the pros and contras...

  16. Critical role of environmental factors in the pathogenesis of psoriasis.

    Science.gov (United States)

    Zeng, Jinrong; Luo, Shuaihantian; Huang, Yumeng; Lu, Qianjin

    2017-08-01

    Psoriasis is a common cutaneous disease with multifactorial etiology including genetic and non-genetic factors, such as drugs, smoking, drinking, diet, infection and mental stress. Now, the role of the interaction between environmental factors and genetics are considered to be a main factor in the pathogenesis of psoriasis. However, it is a challenge to explore the mechanisms how the environmental factors break the body balance to affect the onset and development of psoriasis. In this article, we review the pathogenesis of psoriasis and summarize numerous clinical data to reveal the association between environmental factors and psoriasis. In addition, we focus on the mechanisms of environmental risk factors impact on psoriasis and provide a series of potential treatments against environmental risk factors. © 2017 Japanese Dermatological Association.

  17. Critical role of NKT cells in posttransplant alloantibody production.

    Science.gov (United States)

    Zimmerer, J M; Swamy, P; Sanghavi, P B; Wright, C L; Abdel-Rasoul, M; Elzein, S M; Brutkiewicz, R R; Bumgardner, G L

    2014-11-01

    We previously reported that posttransplant alloantibody production in CD8-deficient hosts is IL-4+ CD4+ T cell-dependent and IgG1 isotype-dominant. The current studies investigated the hypothesis that IL-4-producing natural killer T cells (NKT cells) contribute to maximal alloantibody production. To investigate this, alloantibody levels were examined in CD8-deficient WT, CD1d KO and Jα18 KO transplant recipients. We found that the magnitude of IgG1 alloantibody production was critically dependent on the presence of type I NKT cells, which are activated by day 1 posttransplant. Unexpectedly, type I NKT cell contribution to enhanced IgG1 alloantibody levels was interferon-γ-dependent and IL-4-independent. Cognate interactions between type I NKT and B cells alone do not stimulate alloantibody production. Instead, NKT cells appear to enhance maturation of IL-4+ CD4+ T cells. To our knowledge, this is the first report to substantiate a critical role for type I NKT cells in enhancing in vivo antibody production in response to endogenous antigenic stimuli. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  18. NUMERICAL ANALYSIS OF THE CRITICAL STATE OF THIN-WALLED STRUCTURE WITH Z-PROFILE CROSS SECTION

    Directory of Open Access Journals (Sweden)

    Patryk Różyło

    2017-03-01

    Full Text Available The object of the study was the thin-walled profile with Z-shaped cross section made of the carbon-epoxy composite. Material model was prepared based on the implemented orthotropic properties. The purpose of study was to determine the value of the critical load at which buckling occurs, the form of buckling and operating characteristics in critical condition. In order to achieve this numerical analysis were carried out. Additionally, the effects of the modification in arrangement of layers of the laminate to the stability and strength of thin-walled composite structures was presented. Numerical studies were carried out using commercial simulation software - ABAQUS®. Within the FEM research, both forms of buckling and the associated critical load, dependent on the configuration the layers of the composite were achieved. Analysis of the obtained results, allowed the evaluation of the structure's work in relation to the level of energy consumption or rigidity estimation. In the paper only numerical simulations of the critical state were conducted.

  19. ROLE, INTERESTS AND CRITICS OF CREDIT RATING AGENCIES

    Directory of Open Access Journals (Sweden)

    Suzana Baresa

    2012-06-01

    Full Text Available Key role of credit rating agencies is reducing the asymmetry information about credit quality (of governments, business entities or securities between issuers and investors, and ensuring a common standard of measuring the creditworthiness. Credit rating agencies are engaged in the sale of opinions about creditworthiness in the form of an alphabetical letter or symbol, which represents a unique ranking. Their opinion is not a guarantee, but it largely dictates the costs and the profits in the financial markets. This work shows the influence of credit rating agencies to investors and publishers, and their role as market regulators. Conflict of interest is a fundamental problem, which is caused by their way of doing business, it arises from their two main objectives: profit and market regulation, which will be explored in the work. Looking back in history credit rating agencies often selected goal of making a profit at the cost of market regulation, therefore they have caused the collapse of the market, and founded themselves criticized by the public.

  20. Numerical Study of the Critical Impact Velocity in Shear. Appendix Number 1

    National Research Council Canada - National Science Library

    Klosak, M

    1996-01-01

    .... A numerical study of impact shearing of a layer has been performed by the FE code ABAQUS. It was intended to verify available experimental results for VAR 4340 steel 52 HRC, obtained by direct...

  1. The critical role of myostatin in differentiation of sheep myoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chenxi [College of Life Science and Technology, Xinjiang University, Urumqi (China); Xinjiang Laboratory of Animal Biotechnology, Urumqi (China); Li, Wenrong; Zhang, Xuemei; Zhang, Ning; He, Sangang; Huang, Juncheng [Xinjiang Laboratory of Animal Biotechnology, Urumqi (China); Laboratory of Grass-fed Animal Genetics, Breeding and Reproduction of Ministry of Agriculture, Urumqi (China); Animal Biotechnological Research Center, Xinjiang Academy of Animal Science, Urumqi (China); Ge, Yubin [The State Engineering Laboratory of AIDS Vaccine, College of Life Science, Jilin University, Changchun (China); Liu, Mingjun, E-mail: xjlmj2004@yahoo.com.cn [Xinjiang Laboratory of Animal Biotechnology, Urumqi (China); Laboratory of Grass-fed Animal Genetics, Breeding and Reproduction of Ministry of Agriculture, Urumqi (China); Animal Biotechnological Research Center, Xinjiang Academy of Animal Science, Urumqi (China)

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer Identification of the effective and specific shRNA to knockdown MSTN. Black-Right-Pointing-Pointer Overexpression of MSTN reversibly suppressed myogenic differentiation. Black-Right-Pointing-Pointer shRNA knockdown of endogenous MSTN promoted ovine myoblast differentiation. Black-Right-Pointing-Pointer MSTN inhibits myogenic differentiation through down-regulation of MyoD and Myogenin and up-regulation of Smad3. Black-Right-Pointing-Pointer Provides a promise for the generation of transgenic sheep to improve meat productivity. -- Abstract: Myostatin [MSTN, also known as growth differentiation factor 8 (GDF8)], is an inhibitor of skeletal muscle growth. Blockade of MSTN function has been reported to result in increased muscle mass in mice. However, its role in myoblast differentiation in farm animals has not been determined. In the present study, we sought to determine the role of MSTN in the differentiation of primary sheep myoblasts. We found that ectopic overexpression of MSTN resulted in lower fusion index in sheep myoblasts, which indicated the repression of myoblast differentiation. This phenotypic change was reversed by shRNA knockdown of the ectopically expressed MSTN in the cells. In contrast, shRNA knockdown of the endogenous MSTN resulted in induction of myogenic differentiation. Additional studies revealed that the induction of differentiation by knocking down the ectopically or endogenously expressed MSTN was accompanied by up-regulation of MyoD and myogenin, and down-regulation of Smad3. Our results demonstrate that MSTN plays critical role in myoblast differentiation in sheep, analogous to that in mice. This study also suggests that shRNA knockdown of MSTN could be a potentially promising approach to improve sheep muscle growth, so as to increase meat productivity.

  2. The critical role of myostatin in differentiation of sheep myoblasts

    International Nuclear Information System (INIS)

    Liu, Chenxi; Li, Wenrong; Zhang, Xuemei; Zhang, Ning; He, Sangang; Huang, Juncheng; Ge, Yubin; Liu, Mingjun

    2012-01-01

    Highlights: ► Identification of the effective and specific shRNA to knockdown MSTN. ► Overexpression of MSTN reversibly suppressed myogenic differentiation. ► shRNA knockdown of endogenous MSTN promoted ovine myoblast differentiation. ► MSTN inhibits myogenic differentiation through down-regulation of MyoD and Myogenin and up-regulation of Smad3. ► Provides a promise for the generation of transgenic sheep to improve meat productivity. -- Abstract: Myostatin [MSTN, also known as growth differentiation factor 8 (GDF8)], is an inhibitor of skeletal muscle growth. Blockade of MSTN function has been reported to result in increased muscle mass in mice. However, its role in myoblast differentiation in farm animals has not been determined. In the present study, we sought to determine the role of MSTN in the differentiation of primary sheep myoblasts. We found that ectopic overexpression of MSTN resulted in lower fusion index in sheep myoblasts, which indicated the repression of myoblast differentiation. This phenotypic change was reversed by shRNA knockdown of the ectopically expressed MSTN in the cells. In contrast, shRNA knockdown of the endogenous MSTN resulted in induction of myogenic differentiation. Additional studies revealed that the induction of differentiation by knocking down the ectopically or endogenously expressed MSTN was accompanied by up-regulation of MyoD and myogenin, and down-regulation of Smad3. Our results demonstrate that MSTN plays critical role in myoblast differentiation in sheep, analogous to that in mice. This study also suggests that shRNA knockdown of MSTN could be a potentially promising approach to improve sheep muscle growth, so as to increase meat productivity.

  3. On the Critical Role of Divergent Selection in Evolvability

    Directory of Open Access Journals (Sweden)

    Joel Lehman

    2016-08-01

    Full Text Available An ambitious goal in evolutionary robotics is to evolve increasingly complex robotic behaviors with minimal human design effort. Reaching this goal requires evolutionary algorithms that can unlock from genetic encodings their latent potential for evolvability. One issue clouding this goal is conceptual confusion about evolvability, which often obscures the aspects of evolvability that are important or desirable. The danger from such confusion is that it may establish unrealistic goals for evolvability that prove unproductive in practice. An important issue separate from conceptual confusion is the common misalignment between selection and evolvability in evolutionary robotics. While more expressive encodings can represent higher-level adaptations (e.g. sexual reproduction or developmental systems that increase long-term evolutionary potential (i.e. evolvability, realizing such potential requires gradients of fitness and evolvability to align. In other words, selection is often a critical factor limiting increasing evolvability. Thus, drawing from a series of recent papers, this article seeks to both (1 clarify and focus the ways in which the term evolvability is used within artificial evolution, and (2 argue for the importance of one type of selection, i.e. divergent selection, for enabling evolvability. The main argument is that there is a fundamental connection between divergent selection and evolvability (on both the individual and population level that does not hold for typical goal-oriented selection. The conclusion is that selection pressure plays a critical role in realizing the potential for evolvability, and that divergent selection in particular provides a principled mechanism for encouraging evolvability in artificial evolution.

  4. Numerical study of criticality of the slab reactors with three regions in one-group transport theory

    International Nuclear Information System (INIS)

    Santos, A. dos.

    1979-01-01

    The criticality of slab reactors consisting of core, blanket, and reflector is studied numerically based on the singular-eigenfunction-expansion method in one-group transport theory. The purpose of this work is three-fold: (1) it is shown that the three-media problem can be converted, using a recently developed method, to a set of regular integral equations for the expansion coefficients, such that numerical solutions can be obtained for the first time based on an exact theory; (2) highly accurate numerical results that can serve as standards of comparison for various approximate methods are reported for representative sets of parameters; and (3) the accuracy of the P sub(N) approximation, one of the more often used methods, is analyzed compared to the exact results [pt

  5. [Critical role of clinical laboratories in hospital infection control].

    Science.gov (United States)

    Yagi, Tetsuya

    2010-11-01

    The hospital infection control and prevention is recognized to be more and more important according to the advances in modern medical treatment and care. Clinical microbiology laboratory play critical roles in the hospital infection control as a member of infection control team (ICT). They are the first in a hospital to identify outbreak of MRSA in NICU and molecular epidemiological analysis of the isolates lead proper intervention of ICT to the concerned ward. From a viewpoint of infectious disease specialist, rapid and precise microbiological information is essential for the appropriate diagnosis and treatment of infectious diseases. Each medical technologist need to make efforts to understand the characteristics of the examinations for infectious diseases and send out information useful for clinical practices. In our hospital, with the participation of all members of medical technologists, rapid reporting system was developed for blood culture examinations, which greatly contribute to the appropriate treatment of bloodstream infections. Collaborations of clinical microbiology laboratory with other members of ICT realize high quality hospital infection control. They also need to be aware of themselves as good practitioners of infection control measures to prevent hospital infections.

  6. Numerical prediction of a dip effect in the critical current density

    International Nuclear Information System (INIS)

    Al Khawaja, U.; Benkraouda, M.; Obaidat, I.M.

    2007-01-01

    We have conducted extensive series of molecular dynamic simulations on the properties of the critical current density in systems with periodic square arrays of pinning sites. The density of the pinning sites was kept fixed while the density of vortices, pinning strength, and temperature were varied several times. At zero temperature, we have observed a substantial dip in the critical current density that occurs only at a fixed value of the vortex density and for specific values of pinning strength. We have found that the occurrence of the dip depends mainly on the initial positions of the vortices with respect to the positions of the pinning sites. At the dip, we have found that the interstitial vortices form moving channels leading to the observed drop in the critical current density

  7. Numerical solution of critical state in superconductivity by finite element software

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Z; Campbell, A M; Coombs, T A [Cambridge University Engineering Department, Trumpington Street, Cambridge CB2 1PZ (United Kingdom)

    2006-12-15

    A numerical method is proposed to analyse the electromagnetic behaviour of systems including high-temperature superconductors (HTSCs) in time-varying external fields and superconducting cables carrying AC transport current. The E-J constitutive law together with an H-formulation is used to calculate the current distribution and electromagnetic fields in HTSCs, and the magnetization of HTSCs; then the forces in the interaction between the electromagnet and the superconductor and the AC loss of the superconducting cable can be obtained. This numerical method is based on solving the partial differential equations time dependently and is adapted to the commercial finite element software Comsol Multiphysics 3.2. The advantage of this method is to make the modelling of the superconductivity simple, flexible and extendable.

  8. Theoretical, experimental and numerical diagnose of critical power point of thermoelectric generators

    DEFF Research Database (Denmark)

    Chen, Min; Gao, Xin

    2014-01-01

    of the critical power point in the series and parallel TEM arrays. Secondly, experiments of a series-parallel hybrid interconnected TEG are presented to clearly quantify the theoretical analyses. Finally, the hierarchical simulation, based on the SPICE (simulation program with integrated circuit emphasis...

  9. Role of Glucagon in Catabolism and Muscle Wasting of Critical Illness and Modulation by Nutrition

    DEFF Research Database (Denmark)

    Thiessen, Steven E; Derde, Sarah; Derese, Inge

    2017-01-01

    of glucagon and its metabolic role during critical illness is lacking. OBJECTIVES: To evaluate whether macronutrient infusion can suppress plasma glucagon during critical illness and study the role of illness-induced glucagon abundance in the disturbed glucose, lipid, and amino acid homeostasis and in muscle...... wasting during critical illness. METHODS: In human and mouse studies, we infused macronutrients and manipulated glucagon availability up and down to investigate its acute and chronic metabolic role during critical illness. MEASUREMENTS AND MAIN RESULTS: In critically ill patients, infusing glucose...

  10. Critical technologies: The role of chemistry and chemical engineering

    International Nuclear Information System (INIS)

    1992-01-01

    The purpose of this report is to identify and illustrate key contributions of chemical and chemical engineering research to the development of technologies that have been deemed critical to the economy, security, and well-being of our nation. The report surveys a wide range of vital technologies that are heavily reliant or even critically dependent on chemical or chemical engineering research. Examples were taken from the fields of materials, manufacturing, energy, transportation, public health, information and communications, and the environment. While loosely following the structure of the critical technologies report of the NCTP, our committee decided on a different approach, that of using examples backed up by extensive illustrations

  11. Multiple attractors and critical parameters and how to find them numerically: the right, the wrong and the gambling way

    Science.gov (United States)

    True, Hans

    2013-03-01

    In recent years, several authors have proposed 'easier numerical methods' to find the critical speed in railway dynamical problems. Actually, the methods do function in some cases, but in most cases it is really a gamble. In this article, the methods are discussed and the pros and contras are commented upon. I also address the questions when a linearisation is allowed and the curious fact that the hunting motion is more robust than the ideal stationary-state motion on the track. Concepts such as 'multiple attractors', 'subcritical and supercritical bifurcations', 'permitted linearisation', 'the danger of running at supercritical speeds' and 'chaotic motion' are addressed.

  12. Numerical verification/validation of the theory of coupled reactors for deuterium critical assembly, using MCNP5 and Serpent codes

    International Nuclear Information System (INIS)

    Hussein, M.S; Lewis, B.J.; Bonin, H.W.

    2013-01-01

    The theory of multipoint coupled reactors developed by multi-group transport is verified by using the probabilistic transport code MCNP5 and the continuous-energy Monte Carlo reactor physics burnup calculation Serpent code. The verification was performed by calculating the multiplication factors (or criticality factors) and coupling coefficients for a two-region test reactor known as the Deuterium Critical Assembly, DCA. The multiplication factors k eff calculated numerically and independently from simulations of the DCA by MCNP5 and Serpent codes are compared with the multiplication factors k eff calculated based on the coupled reactor theory. Excellent agreement was obtained between the multiplication factors k eff calculated with the Serpent code, with MCNP5, and from the coupled reactor theory. This analysis demonstrates that the Serpent code is valid for the multipoint coupled reactor calculations. (author)

  13. Numerical verification/validation of the theory of coupled reactors for deuterium critical assembly, using MCNP5 and Serpent codes

    Energy Technology Data Exchange (ETDEWEB)

    Hussein, M.S, E-mail: mohamed.hussein@rmc.ca [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada); Lewis, B.J., E-mail: Brent.Lewis@uoit.ca [Univ. of Ontario Inst. of Technology, Faculty of Energy Systems and Nuclear Science, Oshawa, Ontario (Canada); Bonin, H.W., E-mail: bonin-h@rmc.ca [Royal Military College of Canada, Dept. of Chemistry and Chemical Engineering, Kingston, Ontario (Canada)

    2013-07-01

    The theory of multipoint coupled reactors developed by multi-group transport is verified by using the probabilistic transport code MCNP5 and the continuous-energy Monte Carlo reactor physics burnup calculation Serpent code. The verification was performed by calculating the multiplication factors (or criticality factors) and coupling coefficients for a two-region test reactor known as the Deuterium Critical Assembly, DCA. The multiplication factors k{sub eff} calculated numerically and independently from simulations of the DCA by MCNP5 and Serpent codes are compared with the multiplication factors k{sub eff} calculated based on the coupled reactor theory. Excellent agreement was obtained between the multiplication factors k{sub eff} calculated with the Serpent code, with MCNP5, and from the coupled reactor theory. This analysis demonstrates that the Serpent code is valid for the multipoint coupled reactor calculations. (author)

  14. Role of criticality models in ANSI standards for nuclear criticality safety

    International Nuclear Information System (INIS)

    Thomas, J.T.

    1976-01-01

    Two methods used in nuclear criticality safety evaluations in the area of neutron interaction among subcritical components of fissile materials are the solid angle and surface density techniques. The accuracy and use of these models are briefly discussed

  15. Numerical modeling of laser-driven ion acceleration from near-critical gas targets

    Science.gov (United States)

    Tatomirescu, Dragos; Vizman, Daniel; d’Humières, Emmanuel

    2018-06-01

    In the past two decades, laser-accelerated ion sources and their applications have been intensely researched. Recently, it has been shown through experiments that proton beams with characteristics comparable to those obtained with solid targets can be obtained from gaseous targets. By means of particle-in-cell simulations, this paper studies in detail the effects of a near-critical density gradient on ion and electron acceleration after the interaction with ultra high intensity lasers. We can observe that the peak density of the gas jet has a significant influence on the spectrum features. As the gas jet density increases, so does the peak energy of the central quasi-monoenergetic ion bunch due to the increase in laser absorption while at the same time having a broadening effect on the electron angular distribution.

  16. Numerical estimation of wall friction ratio near the pseudo-critical point with CFD-models

    International Nuclear Information System (INIS)

    Angelucci, M.; Ambrosini, W.; Forgione, N.

    2013-01-01

    In this paper, the STAR-CCM+ CFD code is used in the attempt to reproduce the values of friction factor observed in experimental data at supercritical pressures at various operating conditions. A short survey of available data and correlations for smooth pipe friction in circular pipes puts the basis for the discussion, reporting observed trends of friction factor in the liquid-like and the gas-like regions and within the transitional region across the pseudo-critical temperature. For smooth pipes, a general decrease of the friction factor in the transitional region is reported, constituting one of the relevant effects to be predicted by the computational fluid-dynamic models. A limited number of low-Reynolds number models are adopted, making use of refined near-wall discretisation as required by the constraint y + < 1 at the wall. In particular, the Lien k–ε and the SST k–ω models are considered. The values of the wall shear stress calculated by the code are then post-processed on the basis of bulk fluid properties to obtain the Fanning and then the Darcy–Weisbach friction factors, based on their classical definitions. The obtained values are compared with those provided by experimental tests and correlations, finding a reasonable qualitative agreement. Expectedly, the agreement is better in the gas-like and liquid-like regions, where fluid property changes are moderate, than in the transitional region, where the trends provided by available correlations are reproduced only in a qualitative way

  17. Numerical investigations on contactless methods for measuring critical current density in HTS: application of modified constitutive-relation method

    International Nuclear Information System (INIS)

    Kamitani, A.; Takayama, T.; Itoh, T.; Ikuno, S.

    2011-01-01

    A fast method is proposed for calculating the shielding current density in an HTS. The J-E constitutive relation is modified so as not to change the solution. A numerical code is developed on the basis of the proposed method. The permanent magnet method is successfully simulated by means of the code. A fast method has been proposed for calculating the shielding current density in a high-temperature superconducting thin film. An initial-boundary-value problem of the shielding current density cannot be always solved by means of the Runge-Kutta method even when an adaptive step-size control algorithm is incorporated to the method. In order to suppress an overflow in the algorithm, the J-E constitutive relation is modified so that its solution may satisfy the original constitutive relation. A numerical code for analyzing the shielding current density has been developed on the basis of this method and, as an application of the code, the permanent magnet method for measuring the critical current density has been investigated numerically.

  18. Management by Textbook: The Role of Textbooks in Developing Critical Thinking

    Science.gov (United States)

    Errington, Alison; Bubna-Litic, David

    2015-01-01

    Critical thinking is widely regarded as a crucial capability for competent management and also for any leadership role in society. In this article, we ask, "How do textbooks play a role in the weakness of many management graduates' critical thinking skills?" Management teachers can find plentiful advice about best teaching practices, yet…

  19. The Limited Role of Journalism Professors in Direct Media Criticism.

    Science.gov (United States)

    Bass, Abraham Z.

    This paper discusses reasons why few journalism professors are personally confronting the news media with criticism or praise. One of the primary reasons for this is that journalism professors may fear retribution or keep inbred ties with the media or be following academic tradition. A survey was conducted in Spring 1975 for this report. The…

  20. Action Simulation Plays a Critical Role in Deceptive Action Recognition

    NARCIS (Netherlands)

    Tidoni, Emmanuele; Borgomaneri, Sara; Di Pellegrino, Giuseppe; Avenanti, Alessio

    2013-01-01

    The ability to infer deceptive intents from nonverbal behavior is critical for social interactions. By combining single-pulse and repetitive transcranial magnetic stimulation (TMS) in healthy humans, we provide both correlational and causative evidence that action simulation is actively involved in

  1. Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets.

    Science.gov (United States)

    Sun, Na; Keep, Richard F; Hua, Ya; Xi, Guohua

    2016-10-01

    Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

  2. Spatiotemporal mechanical variation reveals critical role for rho kinase during primitive streak morphogenesis.

    Science.gov (United States)

    Henkels, Julia; Oh, Jaeho; Xu, Wenwei; Owen, Drew; Sulchek, Todd; Zamir, Evan

    2013-02-01

    Large-scale morphogenetic movements during early embryo development are driven by complex changes in biochemical and biophysical factors. Current models for amniote primitive streak morphogenesis and gastrulation take into account numerous genetic pathways but largely ignore the role of mechanical forces. Here, we used atomic force microscopy (AFM) to obtain for the first time precise biomechanical properties of the early avian embryo. Our data reveal that the primitive streak is significantly stiffer than neighboring regions of the epiblast, and that it is stiffer than the pre-primitive streak epiblast. To test our hypothesis that these changes in mechanical properties are due to a localized increase of actomyosin contractility, we inhibited actomyosin contractility via the Rho kinase (ROCK) pathway using the small-molecule inhibitor Y-27632. Our results using several different assays show the following: (1) primitive streak formation was blocked; (2) the time-dependent increase in primitive streak stiffness was abolished; and (3) convergence of epiblast cells to the midline was inhibited. Taken together, our data suggest that actomyosin contractility is necessary for primitive streak morphogenesis, and specifically, ROCK plays a critical role. To better understand the underlying mechanisms of this fundamental process, future models should account for the findings presented in this study.

  3. Botrytis cinerea protein O-mannosyltransferases play critical roles in morphogenesis, growth, and virulence.

    Directory of Open Access Journals (Sweden)

    Mario González

    Full Text Available Protein O-glycosylation is crucial in determining the structure and function of numerous secreted and membrane-bound proteins. In fungi, this process begins with the addition of a mannose residue by protein O-mannosyltransferases (PMTs in the lumen side of the ER membrane. We have generated mutants of the three Botrytis cinerea pmt genes to study their role in the virulence of this wide-range plant pathogen. B. cinerea PMTs, especially PMT2, are critical for the stability of the cell wall and are necessary for sporulation and for the generation of the extracellular matrix. PMTs are also individually required for full virulence in a variety of hosts, with a special role in the penetration of intact plant leaves. The most significant case is that of grapevine leaves, whose penetration requires the three functional PMTs. Furthermore, PMT2 also contributes significantly to fungal adherence on grapevine and tobacco leaves. Analysis of extracellular and membrane proteins showed significant changes in the pattern of protein secretion and glycosylation by the pmt mutants, and allowed the identification of new protein substrates putatively glycosylated by specific PMTs. Since plants do no possess these enzymes, PMTs constitute a promising target in the development of novel control strategies against B. cinerea.

  4. The Critical Role of Positive Incentives for Reducing Insider Threats

    Science.gov (United States)

    2016-12-01

    such skills . Creating a technical track of advancement separate from the management track can help ameliorate these problems. Effective Communication ...Omar, F.; Halim, F. W.; & Hafidz, S. W. M. The Mediating Role of Organizational- Based Self - Esteem in Perceived Organizational Support and... Esteem Relate to Deviant Behavior? The Role of Contingencies of Self -Worth. Journal of Applied Psychology. Volume 94. Number 5. September 2009. Page

  5. The role of melatonin in anaesthesia and critical care

    Directory of Open Access Journals (Sweden)

    Madhuri S Kurdi

    2013-01-01

    Full Text Available Melatonin is a neurohormone secreted by the pineal gland. It is widely present in both plant and animal sources. In several countries, it is sold over the counter as tablets and as food supplement or additive. Currently, it is most often used to prevent jet lag and to induce sleep. It has been and is being used in several clinical trials with different therapeutic approaches. It has sedative, analgesic, anti-inflammatory, anti-oxidative and chronobiotic effects. In the present review, the potential therapeutic benefits of melatonin in anaesthesia and critical care are presented. This article aims to review the physiological properties of melatonin and how these could prove useful for several clinical applications in perioperative management, critical care and pain medicine. The topic was handsearched from textbooks and journals and electronically from PubMed, and Google scholar using text words.

  6. The role of melatonin in anaesthesia and critical care.

    Science.gov (United States)

    Kurdi, Madhuri S; Patel, Tushar

    2013-03-01

    Melatonin is a neurohormone secreted by the pineal gland. It is widely present in both plant and animal sources. In several countries, it is sold over the counter as tablets and as food supplement or additive. Currently, it is most often used to prevent jet lag and to induce sleep. It has been and is being used in several clinical trials with different therapeutic approaches. It has sedative, analgesic, anti-inflammatory, anti-oxidative and chronobiotic effects. In the present review, the potential therapeutic benefits of melatonin in anaesthesia and critical care are presented. This article aims to review the physiological properties of melatonin and how these could prove useful for several clinical applications in perioperative management, critical care and pain medicine. The topic was handsearched from textbooks and journals and electronically from PubMed, and Google scholar using text words.

  7. The Critical Role of Organic Chemistry in Drug Discovery.

    Science.gov (United States)

    Rotella, David P

    2016-10-19

    Small molecules remain the backbone for modern drug discovery. They are conceived and synthesized by medicinal chemists, many of whom were originally trained as organic chemists. Support from government and industry to provide training and personnel for continued development of this critical skill set has been declining for many years. This Viewpoint highlights the value of organic chemistry and organic medicinal chemists in the complex journey of drug discovery as a reminder that basic science support must be restored.

  8. Action simulation plays a critical role in deceptive action recognition.

    Science.gov (United States)

    Tidoni, Emmanuele; Borgomaneri, Sara; di Pellegrino, Giuseppe; Avenanti, Alessio

    2013-01-09

    The ability to infer deceptive intents from nonverbal behavior is critical for social interactions. By combining single-pulse and repetitive transcranial magnetic stimulation (TMS) in healthy humans, we provide both correlational and causative evidence that action simulation is actively involved in the ability to recognize deceptive body movements. We recorded motor-evoked potentials during a faked-action discrimination (FAD) task: participants watched videos of actors lifting a cube and judged whether the actors were trying to deceive them concerning the real weight of the cube. Seeing faked actions facilitated the observers' motor system more than truthful actions in a body-part-specific manner, suggesting that motor resonance was sensitive to deceptive movements. Furthermore, we found that TMS virtual lesion to the anterior node of the action observation network, namely the left inferior frontal cortex (IFC), reduced perceptual sensitivity in the FAD task. In contrast, no change in FAD task performance was found after virtual lesions to the left temporoparietal junction (control site). Moreover, virtual lesion to the IFC failed to affect performance in a difficulty-matched spatial-control task that did not require processing of spatiotemporal (acceleration) and configurational (limb displacement) features of seen actions, which are critical to detecting deceptive intent in the actions of others. These findings indicate that the human IFC is critical for recognizing deceptive body movements and suggest that FAD relies on the simulation of subtle changes in action kinematics within the motor system.

  9. Numerical calculation procedure for criticality parameters of the two-zone reflected reactor with flat central zone

    International Nuclear Information System (INIS)

    Bosevski, T.; Strugar, P.

    1966-10-01

    In determining the criticality parameters of a two-zone reactor with flat central zone one encounters a numerical problem requiring the solution of a system of two non-linear equations. To solve them the Newton method, which proved convenient, was used n this work. By comparing our results with those reported one obtains about 5% smaller values of both the radius of the flat zone and of the radial buckling of the outer zone. This discrepancy probably results from some approximations used in solving the same system of equations used in solving the same system of equations where the procedure form was applied, whereas the calculation time is by one order of magnitude smaller

  10. Numerical and Experimental Investigation on the Structural Behaviour of a Horizontal Stabilizer under Critical Aerodynamic Loading Conditions

    Directory of Open Access Journals (Sweden)

    R. Sepe

    2017-01-01

    Full Text Available The aim of the proposed research activity is to investigate the mechanical behaviour of a part of aerospace horizontal stabilizer, made of composite materials and undergoing static loads. The prototype design and manufacturing phases have been carried out in the framework of this research activity. The structural components of such stabilizer are made of composite sandwich panels (HTA 5131/RTM 6 with honeycomb core (HRH-10-1/8-4.0; the sandwich skins have been made by means of Resin Transfer Moulding (RTM process. In order to assess the mechanical strength of this stabilizer, experimental tests have been performed. In particular, the most critical inflight recorded aerodynamic load has been experimentally reproduced and applied on the stabilizer. A numerical model, based on the Finite Element Method (FEM and aimed at reducing the experimental effort, has been preliminarily developed to calibrate amplitude, direction, and distribution of an equivalent and simpler load vector to be used in the experimental test. The FEM analysis, performed by using NASTRAN code, has allowed modelling the skins of the composite sandwich plates by definition of material properties and stack orientation of each lamina, while the honeycomb core has been modelled by using an equivalent orthotropic plate. Numerical and experimental results have been compared and a good agreement has been achieved.

  11. Low-power critical facilities: their role in the nuclear renaissance

    International Nuclear Information System (INIS)

    Didsbury, R.

    2011-01-01

    This paper discusses the role of low power critical facilities and their role in the nuclear renaissance. It outline the role of human capital in some detail. sufficient conditions for the renaissance are that nuclear power is safe, sustainable, economical and proliferation resistant.

  12. Renormalization of weak noises of arbitrary shape for one-dimensional critical dynamical systems Announcement of results and numerical explorations

    CERN Document Server

    Diaz-Espinosa, O

    2006-01-01

    We study the effect of noise on one--dimensional critical dynamical systems (that is, maps with a renormalization theory). We consider in detail two examples of such dynamical systems: unimodal maps of the interval at the accumulation of period--doubling and smooth homeomorphisms of the circle with a critical point and with golden mean rotation number. We show that, if we scale the space and the time, several properties of the noise (the cumulants or Wick--ordered moments) satisfy some scaling relations. A consequence of the scaling relations is that a version of the central limit theorem holds. Irrespective of the shape of the initial noise, if the bare noise is weak enough, the effective noise becomes close to Gaussian in several senses that we can make precise. We notice that the conclusions are false for maps with positive Lyapunov exponents. The method of analysis is close in spirit to the study of scaling limits in renormalization theory. We also perform several numerical experiments that confirm the ri...

  13. The Critical Role of Potassium in Plant Stress Response

    Directory of Open Access Journals (Sweden)

    Min Wang

    2013-04-01

    Full Text Available Agricultural production continues to be constrained by a number of biotic and abiotic factors that can reduce crop yield quantity and quality. Potassium (K is an essential nutrient that affects most of the biochemical and physiological processes that influence plant growth and metabolism. It also contributes to the survival of plants exposed to various biotic and abiotic stresses. The following review focuses on the emerging role of K in defending against a number of biotic and abiotic stresses, including diseases, pests, drought, salinity, cold and frost and waterlogging. The availability of K and its effects on plant growth, anatomy, morphology and plant metabolism are discussed. The physiological and molecular mechanisms of K function in plant stress resistance are reviewed. This article also evaluates the potential for improving plant stress resistance by modifying K fertilizer inputs and highlights the future needs for research about the role of K in agriculture.

  14. A critical role for astrocytes in hypercapnic vasodilation in brain

    DEFF Research Database (Denmark)

    Howarth, C; Sutherland, B A; Choi, H B

    2017-01-01

    increases in astrocyte calcium signaling which in turn stimulates COX-1 activity and generates downstream PgE2 production. We demonstrate that astrocyte calcium-evoked production of the vasodilator, PgE2, is critically dependent on brain levels of the antioxidant, glutathione. These data suggest a novel......Cerebral blood flow (CBF) is controlled by arterial blood pressure, arterial CO2, arterial O2, and brain activity and is largely constant in the awake state. Although small changes in arterial CO2 are particularly potent to change CBF (1 mmHg variation in arterial CO2 changes CBF by 3...... in brain slices with in vivo work in rats and C57Bl/6J mice to examine the hemodynamic responses to CO2 and somatosensory stimulation before and after inhibition of astrocytic glutathione and PgE2 synthesis. We demonstrate that hypercapnia (increased CO2) evokes an increase in astrocyte [Ca(2+)]i...

  15. Chronic Student Absenteeism: The Critical Role of School Nurses.

    Science.gov (United States)

    Jacobsen, Kathleen; Meeder, Linda; Voskuil, Vicki R

    2016-05-01

    Routine school attendance is necessary for youth to develop into well-educated, successful adult citizens who will make significant contributions to society. Yet over 5 million students in the United States are chronically absent missing more than 10% of school in a year. The growing problem of chronic absenteeism among youth can be linked to increases in chronic health conditions in childhood such as allergies, asthma, diabetes, and obesity. School nurses are in an ideal position to play a vital role in reducing chronic student absenteeism, enabling youth to achieve their maximum learning potential. However, the role of the school nurse has not historically been recognized as a key factor for assisting youth to be present and regularly engaged in school. This feature article highlights a hospital-funded school nurse program within the state of Michigan that has reduced chronic absenteeism rates by placing school nurses into schools where previously there were none. The program implemented a number of initiatives that were instrumental in increasing the health and safety of students and provides a unique "before and after" glimpse of how school nursing reduces chronic student absenteeism rates and validates the essential role of the nurse within the educational system. © 2016 The Author(s).

  16. Role strain among male RNs in the critical care setting: Perceptions of an unfriendly workplace.

    Science.gov (United States)

    Carte, Nicholas S; Williams, Collette

    2017-12-01

    Traditionally, nursing has been a female-dominated profession. Men employed as registered nurses have been in the minority and little is known about the experiences of this demographic. The purpose of this descriptive, quantitative study was to understand the relationship between the variables of demographics and causes of role strain among male nurses in critical care settings. The Sherrod Role Strain Scale assesses role strain within the context of role conflict, role overload, role ambiguity and role incongruity. Data analysis of the results included descriptive and inferential statistics. Inferential statistics involved the use of repeated measures ANOVA testing for significant difference in the causes of role strain between male nurses employed in critical care settings and a post hoc comparison of specific demographic data using multivariate analyses of variance (MANOVAs). Data from 37 male nurses in critical care settings from the northeast of the United States were used to calculate descriptive statistics standard deviation, mean of the data analysis and results of the repeated ANOVA and the post hoc secondary MANOVA analysis. The descriptive data showed that all participants worked full-time. There was an even split from those participants who worked day shift (46%) vs. night shift (43%), most the participants indicated they had 15 years or more experience as an registered nurse (54%). Significant findings of this study include two causes of role strain in male nurses employed in critical care settings which are: role ambiguity and role overload based on ethnicity. Consistent with previous research findings, the results of this study suggest that male registered nurses employed in critical care settings do experience role strain. The two main causes of role strain in male nurses are role ambiguity and role overload. Copyright © 2017. Published by Elsevier Ltd.

  17. The role of student’s critical asking question in developing student’s critical thinking skills

    Science.gov (United States)

    Santoso, T.; Yuanita, L.; Erman, E.

    2018-01-01

    Questioning means thinking, and thinking is manifested in the form of questions. Research that studies the relationship between questioning and students’ critical thinking skills is little, if any. The aim of this study is to examine how student’s questions skill correlates to student’s critical thinking skills in learning of chemistry. The research design used was one group pretest-posttest design. The participants involved were 94 students, all of whom attended their last semesters, Chemistry Education of Tadulako University. A pre-test was administered to check participants’ ability to ask critical questions and critical thinking skills in learning chemistry. Then, the students were taught by using questioning technique. After accomplishing the lesson, a post-test was given to evaluate their progress. Obtained data were analyzed by using Pair-Samples T.Test and correlation methods. The result shows that the level of the questions plays an important role in critical thinking skills is the question levels of predictive, analysis, evaluation and inference.

  18. Emerging roles of Lipasin as a critical lipid regulator.

    Science.gov (United States)

    Zhang, Ren; Abou-Samra, Abdul B

    2013-03-15

    Patients with metabolic syndrome are at high risk for developing atherosclerotic cardiovascular diseases and diabetes. In addition to total cholesterol, LDL-C and HDL-C, elevated plasma triglycerides (TG) are increasingly recognized as an independent risk factor for cardiovascular diseases. Recently 3 groups independently reported the identification and characterization of a novel blood lipid regulator, Lipasin/RIFL/ANGPTL8, which here is referred to as Lipasin for its lipoprotein lipase inhibition effect and for being a circulating factor denoted by 'in'. Being highly enriched in the liver, Lipasin is a hepatocyte-derived circulating factor that regulates plasma TG levels. Lipasin is nutritionally regulated, as its mRNA levels in liver and fat as well as its protein level in serum are reduced by fasting. Mice deficient for Lipasin have lower serum TG levels; conversely, its adenovirus-mediated overexpression increases serum TG levels, in part, through promoting ANGPTL3 cleavage, releasing its N-terminal domain that inhibits lipoprotein lipase. Lipasin sequence variations are associated with LDL-C and HDL-C concentrations in humans. Being lipogenic, Lipasin is highly induced during adipogenesis. Levels of Lipasin and ANGPTL4 show opposite changes in response to fasting or cold environment. Lipasin, a novel but atypical ANGPTL family member, is emerging as a critical lipid regulator and a potential drug target. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Role of the surface in the critical behavior of finite systems

    Energy Technology Data Exchange (ETDEWEB)

    Duflot, V.; Chomaz, Ph. [Grand Accelerateur National d' Ions Lourds (GANIL), 14 - Caen (France); Gulminelli, F. [Laboratoire de Physique Corpusculaire, LPC-ISMRa, CNRS-IN2P3, 14 - Caen (France)

    2000-07-01

    The role of surfaces in a finite system undergoing a critical phenomenon is discussed in a canonical lattice-gas model. Surfaces are constrained by a mean volume defined via a La grange multiplier. We show that critical fragment size distributions are conserved even in very small systems with surfaces. This implies that critical signals are still relevant in the study of phase transitions in finite systems. (authors)

  20. Role of Email in Intercultural Communication of Criticism in a Chinese English Curriculum Reform Context

    Science.gov (United States)

    Lü, Linqiong

    2018-01-01

    Western teachers working in China often experience cultural conflicts arising from, for instance, the ways that Chinese students perceive face and express criticism. To better understand these face-concerned conflicts, this paper explores the role and significance of email for a group of Chinese students to communicate pedagogical criticism with…

  1. What's My Lane? Identifying the State Government Role in Critical Infrastructure Protection

    OpenAIRE

    Donnelly, Timothy S.

    2012-01-01

    Approved for public release; distribution is unlimited What constitutes an effective Critical Infrastructure and Key Resources (CIKR) protection program for Massachusetts This study evaluates existing literature regarding CIKR to extrapolate an infrastructure protection role for Massachusetts. By reviewing historical events and government strategies regarding infrastructure protection, Chapters I and II will provide scope and context for issues surrounding critical infrastructure. Chapter ...

  2. What’s My Lane? Identifying the State Government Role in Critical Infrastructure Protection

    Science.gov (United States)

    2012-03-01

    Marsh Commission. The GMU research program was developed with Congressional funding, the results of which have produced numerous research papers ...acknowledging that not all attacks or accidents can be prevented, turn to criticality as a crutch —pouring more and more resources into all

  3. The critical role of ethics training in medical education

    Directory of Open Access Journals (Sweden)

    A Nicolaides

    2014-01-01

    Full Text Available When one thinks of the issue of medical ethics the Hippocratic Oath comes to mind. In terms of this oath, one would assume that the goal of medical ethics is to improve the quality of patient care by means of the identification and analysis, and hopefully resolution of any ethical complications that arise in the course of medical practice. This is not always the case and sadly, many Physicians' are unhappy with the practice of medicine and its ethical obligations. Such attitudes may have severe public health implications for the South African medical profession. It is thus essential to provide even more effective ethics training which includes moral reasoning during medical school and residency training. At a time when there appears to be less public confidence in doctors and where practitioner morale is at an all-time low, and patients complain of substandard medical treatment, it is important to reconsider the question of medical ethics. This paper seeks to scrutinize the principles of the Hippocratic Oath and questions whether medical practitioners of contemporary medicine adhere to its principles and are taught ethics during their medical courses. This will provide a greater understanding of the role of modern medical ethics education in promoting ethical practice.

  4. The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension

    Science.gov (United States)

    Prins, Kurt W.; Pritzker, Marc R.; Scandurra, John; Volmers, Karl; Weir, E. Kenneth

    2016-01-01

    The normal pulmonary circulation is a low-pressure, high-compliance system. Pulmonary arterial compliance decreases in the presence of pulmonary hypertension because of increased extracellular matrix/collagen deposition in the pulmonary arteries. Loss of pulmonary arterial compliance has been consistently shown to be a predictor of increased mortality in patients with pulmonary hypertension, even more so than pulmonary vascular resistance in some studies. Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and eventually right ventricular failure. Evidence suggests that decreased pulmonary arterial compliance is a cause rather than a consequence of distal small vessel proliferative vasculopathy. Pulmonary arterial compliance decreases early in the disease process even when pulmonary artery pressure and pulmonary vascular resistance are normal, potentially enabling early diagnosis of pulmonary vascular disease, especially in high-risk populations. With the recognition of the prognostic importance of pulmonary arterial compliance, its impact on right ventricular function, and its contributory role in the development and progression of distal small-vessel proliferative vasculopathy, pulmonary arterial compliance is an attractive target for the treatment of pulmonary hypertension. PMID:26848601

  5. The Critical Role of Institutional Services in Open Access Advocacy

    Directory of Open Access Journals (Sweden)

    Tomasz Neugebauer

    2013-06-01

    Full Text Available This paper examines the development of the Open Access movement in scholarly communication, with particular attention to some of the rhetorical strategies and policy mechanisms used to promote it to scholars and scientists. Despite the majority of journal publishers’ acceptance of author self-archiving practices, and the minimal time commitment required by authors to successfully self-archive their work in disciplinary or institutional repositories, the majority of authors still by and large avoid participation. The paper reviews the strategies and arguments used for increasing author participation in open access, including the role of open access mandates. We recommend a service-oriented approach towards increasing participation in open access, rather than rhetoric that speculates on the benefits that open access will have on text/data mining innovation. In advocating for open access participation, we recommend focusing on its most universal and tangible purpose: increasing public open (gratis access to the published results of publicly funded research. Researchers require strong institutional support to understand the copyright climate of open access self-archiving, user-friendly interfaces and useful metrics, such as repository usage statistics. We recommend that mandates and well-crafted and responsive author support services at universities will ultimately be required to ensure the growth of open access. We describe the mediated deposit service that was developed to support author self-archiving in Spectrum: Concordia University Research Repository. By comparing the number of deposits of non-thesis materials (e.g. articles and conference presentations that were accomplished through the staff-mediated deposit service to the number of deposits that were author-initiated, we demonstrate the relative significance of this service to the growth of the repository.

  6. Role of Brittle Behaviour of Soft Calcarenites Under Low Confinement: Laboratory Observations and Numerical Investigation

    Science.gov (United States)

    Lollino, Piernicola; Andriani, Gioacchino Francesco

    2017-07-01

    The strength decay that occurs in the post-peak stage, under low confinement stress, represents a key factor of the stress-strain behaviour of rocks. However, for soft rocks this issue is generally underestimated or even neglected in the solution of boundary value problems, as for example those concerning the stability of underground cavities or rocky cliffs. In these cases, the constitutive models frequently used in limit equilibrium analyses or more sophisticated numerical calculations are, respectively, rigid-plastic or elastic-perfectly plastic. In particular, most of commercial continuum-based numerical codes propose a variety of constitutive models, including elasticity, elasto-plasticity, strain-softening and elasto-viscoplasticity, which are not exhaustive in simulating the progressive failure mechanisms affecting brittle rock materials, these being characterized by material detachment and crack opening and propagation. As a consequence, a numerical coupling with mechanical joint propagation is needed to cope with fracture mechanics. Therefore, continuum-based applications that treat the simulation of the failure processes of intact rock masses at low stress levels may need the adoption of numerical techniques capable of implementing fracture mechanics and rock brittleness concepts, as it is shown in this paper. This work is aimed at highlighting, for some applications of rock mechanics, the essential role of post-peak brittleness of soft rocks by means of the application of a hybrid finite-discrete element method. This method allows for a proper simulation of the brittle rock behaviour and the related mechanism of fracture propagation. In particular, the paper presents two ideal problems, represented by a shallow underground cave and a vertical cliff, for which the evolution of the stability conditions is investigated by comparing the solutions obtained implementing different brittle material responses with those resulting from the assumption of perfectly

  7. Long-term energy futures: the critical role of technology

    International Nuclear Information System (INIS)

    Grubler, A.

    1999-01-01

    The paper briefly reviews the results of a 5-year study conducted by IIASA jointly with the World Energy Council (WEC) on long term-energy perspectives. After summarizing the study's main findings, the paper addresses the crucial role of technological change in the evolution of long-term energy futures and in responding to key long-term uncertainties in the domains of energy demand growth, economics, as well as environmental protection. Based on most recent empirical and methodological findings, long-term dynamics of technological change portray a number of distinct features that need to be taken account of in technology and energy policy. First, success of innovation efforts and ultimate outcomes of technological are uncertain. Second, new, improved technologies are not a free good, but require continued dedicated efforts. Third, technological knowledge (as resulting from R and D and accumulation of experience, i.e. technological learning) exhibits characteristics of (uncertain) increasing returns. Forth, due to innovation - diffusion lags, technological interdependence, and infrastructure needs (network externalities), rates of change in large-scale energy systems are necessarily slow. This implies acting sooner rather than later as a contigency policy to respond to long-term social, economic and environmental uncertainties, most notably possible climate change. Rather than picking technological 'winners' the results of the IIASA-WEC scenario studies are seen most appropriate to guide technology and R and D portfolio analysis. Nonetheless, robust persistent patterns of technological change invariably occur across all scenarios. Examples of primising groups of technologies are given. The crucial importance of meeting long-energy demand in developing countries, assuring large-scale infrastructure investments, maintaining a strong and diversified R AND D protfolio, as well as to dvise new institutional mechnisms for technology development and diffusion for instance

  8. Role of urodynamics in stress urinary incontinence: A critical appraisal

    Science.gov (United States)

    Yande, Shirish Dattatraya; Joglekar, Omkar Vinay; Joshi, Maya

    2016-01-01

    Introduction: Role of urodynamics prior to surgery of stress urinary incontinence (SUI) is under constant debate. Demonstration of the presence of detrusor overactivity is the only aspect that has been emphasized in the literature so far. We believe that there are number of other factors which may influence the evaluation and in turn the choice of surgical management and prediction of outcome of treatment. They are as follows: (1) Presence of voiding inefficiency, (2) asymptomatic detrusor overactivity, (3) and severity of SUI. These features may complicate the precise evaluation of patients of SUI. The main objective of this study is to analyze the dynamics of leakage and voiding using urodynamics. This study also aims at correlating these findings with clinical information. Materials and Methods: One hundred consecutive cases referred to our center for preoperative evaluation of SUI were recruited in the study prospectively. All patients were interrogated using International Consultation on Incontinence Questionnaire. All patients underwent complete urodynamic evaluation including uroflowmetry, filling cystometry, leak point pressure measurement, and pressure flow studies, according to Good Urodynamic Practice guidelines. Patients’ symptoms were correlated with urodynamic findings, with special emphasis on the presence of detrusor overactivity, severity of SUI, voiding efficiency, and presence of bladder outlet obstruction. Clinical information and urodynamic findings were correlated using Chi-square test. Results: There is a statistically significant correlation between the presence of symptoms of urge urinary incontinence and urodynamic findings of detrusor overactivity at P incontinence (in addition to SUI) and urodynamic findings of intrinsic sphincter deficiency at P incontinence and incidental finding of detrusor overactivity at P urinary incontinence can predictably diagnose detrusor overactivity in these cases. However, the incidence of asymptomatic

  9. Role, perspective and knowledge of Iranian critical care nurses about breaking bad news.

    Science.gov (United States)

    Imanipour, Masoomeh; Karim, Zahra; Bahrani, Naser

    2016-05-01

    Given the issue of caring critically ill patients, nurses are involved in the process of breaking bad news in critical care units, while little research has been conducted on this challenging issue. The purpose of this study was to determine the role, perspective and knowledge of Iranian critical care nurses regarding breaking bad news. This descriptive study was conducted on a sample of 160 nurses working in critical care units of hospitals affiliated to Tehran University of Medical Sciences. Stratified and quota sampling methods were used. The data collection tool was a four-part questionnaire with validity and reliability confirmed via content validity and test-retest, respectively. The study showed that most critical care nurses were involved in breaking bad news, with different roles. The majority of participants (91.2%) had a positive attitude towards involvement of nurses in breaking bad news. In this study, 78.8% of nurses had moderate knowledge about how to break bad news, and only a few had good level of knowledge (16.2%). According to the findings, while critical care nurses took different roles in the process of breaking bad news and they had positive attitude towards participation in this process, yet their knowledge about this process was inadequate. Thus, designing educational programmes to enhance critical care nurses' knowledge and skills in this area seems necessary. Copyright © 2015 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

  10. Exploring the Critical Role of Motivation to Transfer in the Training Transfer Process

    Science.gov (United States)

    Grohmann, Anna; Beller, Johannes; Kauffeld, Simone

    2014-01-01

    The present study aims at exploring the critical role of motivation to transfer within the training transfer process. In a sample of N?=?252 employees of one industrial company, one peer rating and several self-ratings of transfer were used to investigate the mediating role of motivation to transfer in the relationship between training…

  11. Balancing the seen and unseen: Nurse educator as role model for critical thinking.

    Science.gov (United States)

    Raymond, Christy; Profetto-McGrath, Joanne; Myrick, Florence; Strean, William B

    2018-05-04

    Critical thinking is an important indicator of student learning and is an essential outcome of baccalaureate nursing education. The role of nurse educators in the development of students' critical thinking has been overlooked despite the importance of their actions to facilitate critical thinking in nursing education. We used a constructivist grounded theory approach within a larger mixed methods triangulation study to explore how nurse educators revealed their critical thinking in practice. From the grounded theory approach, a model emerged from our research, outlining the important aspects of nurse educators' critical thinking and how it is revealed in the clinical setting. The important categories of this model include: a) fostering the student-educator relationship; b) role modeling critical thinking; c) mobilizing and operationalizing resources; as well as d) balancing factors that impact nurse educators' critical thinking. Our findings inform what is known about nurse educators' critical thinking and how it can be implemented in nurse educators' teaching practice. Given our findings, we offer recommendations for future nursing education practice and research, including the need to apply our findings in additional settings and further develop nurse educators' awareness of their own critical thinking. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  12. Critical Role of Crystalline Anisotropy in the Stability of Cellular Array Structures in Directional Solidification

    International Nuclear Information System (INIS)

    Kopczynski, P.; Rappel, W.; Karma, A.

    1996-01-01

    We calculate numerically the full Floquet-Bloch stability spectrum of cellular array structures in a symmetric model of directional solidification. Our results demonstrate that crystalline anisotropy critically influences the stability of these structures. Without anisotropy, the stability balloon of cells in the plane of wave number and velocity closes near the onset of morphological instability. With a finite, but even small, amount of anisotropy this balloon remains open and a band of stable solutions persists for higher velocities into a deep cell regime. The width of the balloon depends critically on the anisotropy strength. copyright 1996 The American Physical Society

  13. Role of Personality Traits, Learning Styles and Metacognition in Predicting Critical Thinking of Undergraduate Students

    Directory of Open Access Journals (Sweden)

    Soliemanifar O

    2015-04-01

    The aim of this study was to investigate the role of personality traits, learning styles and metacognition in predicting critical thinking. Instrument & Methods: In this descriptive correlative study, 240 students (130 girls and 110 boys of Ahvaz Shahid Chamran University were selected by multi-stage random sampling method. The instruments for collecting data were NEO Five-Factor Inventory, learning style inventory of Kolb (LSI, metacognitive assessment inventory (MAI of Schraw & Dennison (1994 and California Critical Thinking Skills Test (CCTST. The data were analyzed using Pearson correlation coefficient, stepwise regression analysis and Canonical correlation analysis.  Findings: Openness to experiment (b=0.41, conscientiousness (b=0.28, abstract conceptualization (b=0.39, active experimentation (b=0.22, reflective observation (b=0.12, knowledge of cognition (b=0.47 and regulation of cognition (b=0.29 were effective in predicting critical thinking. Openness to experiment and conscientiousness (r2=0.25, active experimentation, abstract conceptualization and reflective observation learning styles (r2=0.21 and knowledge and regulation of cognition metacognitions (r2=0.3 had an important role in explaining critical thinking. The linear combination of critical thinking skills (evaluation, analysis, inference was predictable by a linear combination of dispositional-cognitive factors (openness, conscientiousness, abstract conceptualization, active experimentation, knowledge of cognition and regulation of cognition. Conclusion: Personality traits, learning styles and metacognition, as dispositional-cognitive factors, play a significant role in students' critical thinking.

  14. The Critical Role of Stewardship in Fund Raising: The Coaches vs. Cancer Campaign.

    Science.gov (United States)

    Worley, Debra A.; Little, Jennifer K.

    2002-01-01

    Examines the critical role of stewardship in the process of fund raising. Uses the Coaches vs. Cancer campaign to illustrate the limitations of the public relations ROPE (research, objectives, planning, and evaluation) model in explaining fund raising success, and supports K.S. Kelly's contention that addition of a fifth step to the model, the…

  15. Critical role of Middle East in world petroleum supply and demand

    International Nuclear Information System (INIS)

    Riva, J.P., Jr.

    1992-01-01

    The location, production, and transportation of oil consumed in the world each day is of vital importance to good international relationships. Since most of the remaining world's oil reserves are located in the Persian Gulf, the region's critical role in the future is accordingly over-emphasized

  16. Numerical analysis of the reactivity for the dry lattices above the water level of the critical fuel cores

    International Nuclear Information System (INIS)

    Nauchi, Yasushi; Kameyama, Takanori

    2003-01-01

    Criticality analysis has been performed for dozens of tank type cores in which fuel lattices are loaded vertically and partially immersed in light water. The reactivity effect of dry part of lattices stuck above the critical water level has been calculated using the continuous energy Monte Carlo method. The reactivity effect exceeds 0.8% both for MOX and UOX fuel lattices of large buckling (B z 2 > 0.0025 cm -2 ). It is evaluated that at least 20 cm length of fuel rods above the critical water level has significant reactivity effect. (author)

  17. A Numerical Modelling Study on the Potential Role of Tsunamis in the Biblical Exodus

    Directory of Open Access Journals (Sweden)

    José M. Abril

    2015-07-01

    Full Text Available The reliability of the narrative of the Biblical Exodus has been subject of heated debate for decades. Recent archaeological studies seem to provide new insight of the exodus path, and although with a still controversial chronology, the effects of the Minoan Santorini eruption have been proposed as a likely explanation of the biblical plagues. Particularly, it has been suggested that flooding by the associated tsunamis could explain the first plague and the sea parting. Recent modelling studies have shown that Santorini’s tsunami effects were negligible in the eastern Nile Delta, but the released tectonic stress could have triggered local tsunamigenic sources in sequence. This paper is aimed to a quantitative assessment of the potential role of tsunamis in the biblical parting of the sea. Several “best case” scenarios are tested through the application of a numerical model for tsunami propagation that has been previously validated. The former paleogeographic conditions of the eastern Nile Delta have been implemented based upon recent geological studies; and several feasible local sources for tsunamis are proposed. Tsunamis triggered by submarine landslides of 10–30 km3 could have severely impacted the northern Sinai and southern Levantine coasts but with weak effects in the eastern Nile Delta coastline. The lack of noticeable flooding in this area under the most favorable conditions for tsunamis, along with the time sequence of water elevations, make difficult to accept them as a plausible and literally explanation of the first plague and of the drowning of the Egyptian army in the surroundings of the former Shi-Hor Lagoon.

  18. The role of critical thinking skills and learning styles of university students in their academic performance

    Science.gov (United States)

    GHAZIVAKILI, ZOHRE; NOROUZI NIA, ROOHANGIZ; PANAHI, FARIDE; KARIMI, MEHRDAD; GHOLSORKHI, HAYEDE; AHMADI, ZARRIN

    2014-01-01

    Introduction: The Current world needs people who have a lot of different abilities such as cognition and application of different ways of thinking, research, problem solving, critical thinking skills and creativity. In addition to critical thinking, learning styles is another key factor which has an essential role in the process of problem solving. This study aimed to determine the relationship between learning styles and critical thinking of students and their academic performance in Alborz University of Medical Science. Methods: This cross-correlation study was performed in 2012, on 216 students of Alborz University who were selected randomly by the stratified random sampling. The data was obtained via a three-part questionnaire included demographic data, Kolb standardized questionnaire of learning style and California critical thinking standardized questionnaire. The academic performance of the students was extracted by the school records. The validity of the instruments was determined in terms of content validity, and the reliability was gained through internal consistency methods. Cronbach's alpha coefficient was found to be 0.78 for the California critical thinking questionnaire. The Chi Square test, Independent t-test, one way ANOVA and Pearson correlation test were used to determine relationship between variables. The Package SPSS14 statistical software was used to analyze data with a significant level of pcritical thinking of the students showed that the mean of deductive reasoning and evaluation skills were higher than that of other skills and analytical skills had the lowest mean and there was a positive significant relationship between the students’ performance with inferential skill and the total score of critical thinking skills (pcritical thinking had significant difference between different learning styles. Conclusion: The results of this study showed that the learning styles, critical thinking and academic performance are significantly associated

  19. A creative analysis of the role of practice development facilitators in a critical care environment

    Directory of Open Access Journals (Sweden)

    Tanya Heyns

    2017-10-01

    Full Text Available Practice development focuses on methods to address the quality of care and advance healthcare practices. The role of practice development facilitators to address challenges of delivering evidence-based person-centred care in the critical care environment was determined by using a nominal group technique. Eleven participants from public and private healthcare services reached consensus on seven clusters: theory-practice application, facilitation of learning, increasing collaboration, effective communication, facilitation of change, time management and role modelling. The clusters were visually represented as a hot air balloon. Competence as facilitators is of vital importance to ensure knowledge translation with the aim to improve quality.

  20. Critical thinking of destabilizing interpretations of events and phenomena: the role of economic sciences

    Directory of Open Access Journals (Sweden)

    Тетяна Андріївна Непокупна

    2015-03-01

    Full Text Available This article analyzes the global transformations and their impact on the main society life; the specifics of modern interpretations of events and phenomena, their destabilizing effects on behavior, health and life of humans; the role of economic sciences in the formation of critical thinking as a means of combating ignorance and propaganda, formation of an objective world view that grounded on knowledge

  1. Some Thoughts on the Role of the Critical Intellectual in Contemporary Germany

    Directory of Open Access Journals (Sweden)

    Erich Steiner

    2005-08-01

    Full Text Available The paper starts by relating the notion of the "critical intellectual" to the notion of "agent of social change" on the one hand, and to other potential types of agents of change on the other: women in revolt, artists, exiles and queer agencies. Proceeding to a brief characterisation of the socio-cultural and political context "Germany", we shall explore some meanings of attributes such as post-modern and consumer for contemporary German society and culture, arguing that these are cultural and economic terms, which denote current forms of expression for what continues to be a capitalist economy and a bourgeois democracy. One recurrent question will be what the contours might be of the figure of the "critical intellectual" under present day conditions. This is followed by a brief sketch of the meanings of "kritische(r Intellektuelle(r" in a historical ("geistesgeschichtlicher" perspective, mainly from the enlightenment onwards. We shall move on to a methodologically very different, but complementary, perspective, which is the consideration of current usage of the term with the help of large-scale electronic corpora of spoken language and an on-line search on the web. As we shall see, an important share and quality of the relevant meanings of a term lies in current usage, which may or may not be directly related to what we know from the history of ideas and/ or etymology. I shall then use examples from my own professional field of work for an exploration of what the role of a critical intellectual in a German context might be, discussing the field of natural language technologies. These examples will illustrate the fact that such a role has to involve participation in, rather than exclusively detached contemplation of, the sphere of production. They will also show that the role of the critical intellectual is, indeed, a locus of contestation in several respects. We finally broaden our perspective into a wider set of questions relating to the role

  2. The role of critical thinking skills and learning styles of university students in their academic performance

    Directory of Open Access Journals (Sweden)

    ZOHRE GHAZIVAKILI

    2014-07-01

    Full Text Available Introduction: The current world needs people who have a lot of different abilities such as cognition and application of different ways of thinking, research, problem solving, critical thinking skills and creativity. In addition to critical thinking, learning styles is another key factor which has an essential role in the process of problem solving. This study aimed to determine the relationship between learning styles and critical thinking of students and their academic performance in Alborz University of Medical Sciences. Methods: This cross-correlation study was performed in 2012, on 216 students of Alborz University who were selected randomly by the stratified method. The data was obtained via a three-part questionnaire included demographic data, Kolb standardized questionnaire of learning style and California critical thinking standardized questionnaire. The academic performance of the students was extracted by the school records. The validity of the instruments was determined in terms of content validity, and the reliability was gained through internal consistency methods. Cronbach's alpha coefficient was found to be 0.78 for the California critical thinking questionnaire. The Chi Square test, Independent T-test, one way ANOVA and Pearson Correlation test were used to determine relationship between variables. The Package SPSS14 statistical software was used to analyze data with a significant level of p<0.05. Results: Our findings indicated the significant difference of mean score in four learning style, suggesting university students with convergent learning style have better performance than other groups. Also learning style had a relationship with age, gender, field of study, semester and job. The results about the critical thinking of the students showed that the mean of deductive reasoning and evaluation skills were higher than that of other skills and analytical skills had the lowest mean and there was a positive significant

  3. The role of critical thinking skills and learning styles of university students in their academic performance.

    Science.gov (United States)

    Ghazivakili, Zohre; Norouzi Nia, Roohangiz; Panahi, Faride; Karimi, Mehrdad; Gholsorkhi, Hayede; Ahmadi, Zarrin

    2014-07-01

    The Current world needs people who have a lot of different abilities such as cognition and application of different ways of thinking, research, problem solving, critical thinking skills and creativity. In addition to critical thinking, learning styles is another key factor which has an essential role in the process of problem solving. This study aimed to determine the relationship between learning styles and critical thinking of students and their academic performance in Alborz University of Medical Science. This cross-correlation study was performed in 2012, on 216 students of Alborz University who were selected randomly by the stratified random sampling. The data was obtained via a three-part questionnaire included demographic data, Kolb standardized questionnaire of learning style and California critical thinking standardized questionnaire. The academic performance of the students was extracted by the school records. The validity of the instruments was determined in terms of content validity, and the reliability was gained through internal consistency methods. Cronbach's alpha coefficient was found to be 0.78 for the California critical thinking questionnaire. The Chi Square test, Independent t-test, one way ANOVA and Pearson correlation test were used to determine relationship between variables. The Package SPSS14 statistical software was used to analyze data with a significant level of pstudents with convergent learning style have better performance than other groups. Also learning style had a relationship with age, gender, field of study, semester and job. The results about the critical thinking of the students showed that the mean of deductive reasoning and evaluation skills were higher than that of other skills and analytical skills had the lowest mean and there was a positive significant relationship between the students' performance with inferential skill and the total score of critical thinking skills (pskills and deductive reasoning had significant

  4. Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice.

    Science.gov (United States)

    Fujita, Masaki; Ouchi, Hiroshi; Ikegame, Satoshi; Harada, Eiji; Matsumoto, Takemasa; Uchino, Junji; Nakanishi, Yoichi; Watanabe, Kentaro

    2016-01-01

    COPD is a major cause of chronic morbidity and mortality throughout the world. Although tumor necrosis factor-α (TNF-α) has a critical role in the development of COPD, the role of different TNF receptors (TNFRs) in pulmonary emphysema has not been resolved. We aimed to clarify the role of TNFRs in the development of pulmonary emphysema. TNF-α transgenic mice, a murine model of COPD in which the mice spontaneously develop emphysema with a large increase in lung volume and pulmonary hypertension, were crossed with either TNFR1-deficient mice or TNFR2-deficient mice. After 6 months, the gross appearance of the lung, lung histology, and pulmonary and cardiac physiology were determined. In addition, the relationship between apoptosis and emphysema was investigated. Pulmonary emphysema-like changes disappeared with deletion of TNFR1. However, slight improvements were attained with deletion of TNFR2. Apoptotic cells in the interstitium of the lung were observed in TNF-α transgenic mice. The apoptotic signals through TNFR1 appear critical for the pathogenesis of pulmonary emphysema. In contrast, the inflammatory process has a less important role for the development of emphysema.

  5. Burnout and health among critical care professionals: The mediational role of resilience.

    Science.gov (United States)

    Arrogante, Oscar; Aparicio-Zaldivar, Eva

    2017-10-01

    To analyse the mediational role of resilience in relationships between burnout and health in critical care professionals; to determine relationships among resilience level, three burnout dimensions, and physical/mental health; and to establish demographic differences in psychological variables evaluated. Cross-sectional study. A total of 52 critical care professionals, mainly nurses, were recruited from an intensive care unit of Madrid (Spain). All participants were assessed with the questionnaires 10-item Connor-Davidson Resilience Scale, Maslach Burnout Inventory-Human Services Survey, and Short Form-12 Health Survey. No demographic differences were found. Three burnout dimensions were negatively associated with mental health and resilience. Mediational analyses revealed resilience mediated 1) the relationships between emotional exhaustion and depersonalisation with mental health (partial mediations) and 2) the relationship between personal accomplishment and mental health (total mediation). Resilience minimises and buffers the impact of negative outcomes of workplace stress on mental health of critical care professionals. As a result, resilience prevents the occurrence of burnout syndrome. Resilience improves not only their mental health, but also their ability to practice effectively. It is therefore imperative to develop resilience programs for critical care nurses in nursing schools, universities and health centres. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Contributory Role of Collaborative Assessment in Improving Critical Thinking and Writing

    Directory of Open Access Journals (Sweden)

    Mansoor Fahim

    2014-01-01

    Full Text Available Instilling critical thinking skills in language learners’ mind and enhancing second language writing are gaining momentum in the field of English language teaching. Though some approaches to meeting these objectives have been proposed, review of the literature revealed that the contributory role of collaborative assessment in fostering critical thinking and second language writing has been overlooked to date. Thus, this study was conducted to delve into this issue. To this aim, two intact intermediate EFL classes in Iran, each of which contains 18 learners, were included in the study; they were randomly assigned to Student-Student (S-S collaborative assessment and Teacher-Student (T-S collaborative assessment groups.  After receiving six sessions of treatment, both groups wrote an essay on an IELTS topic. Results of the study indicated that collaborative assessment, regardless of its type, has the potential to foster critical thinking and writing proficiency. Further, it came to light that S-S collaborative assessment group significantly outperformed the T-S collaborative assessment group in terms of gains in critical thinking and writing proficiency. In light of the findings, language teachers are suggested to involve learners in collaborative assessment processes; further, some suggestions are offered at the end to show some fruitful avenues for further research.

  7. The Role of Numerical Methods in the Sensitivity Analysis of a ...

    African Journals Online (AJOL)

    The mathematical modelling of physiochemical interaction in the framework of industrial and environmental physics which relies on an initial value problem is defined by a first order ordinary differential equation. Two numerical methods of studying sensitivity analysis of physiochemical interaction data are developed.

  8. On the Role of Entailment Patterns and Scalar Implicatures in the Processing of Numerals

    Science.gov (United States)

    Panizza, Daniele; Chierchia, Gennaro; Clifton, Charles, Jr.

    2009-01-01

    There has been much debate, in both the linguistics and the psycholinguistics literature, concerning numbers and the interpretation of number denoting determiners ("numerals"). Such debate concerns, in particular, the nature and distribution of upper-bounded ("exact") interpretations vs. lower-bounded ("at-least") construals. In the present paper…

  9. Role of vegetation in formation of radiation fog: A numerical study

    Czech Academy of Sciences Publication Activity Database

    Potužníková, Kateřina; Sedlák, Pavel

    2004-01-01

    Roč. 23, Suppl. 2 (2004), s. 39-45 ISSN 1335-342X Institutional research plan: CEZ:AV0Z3042911 Keywords : radiation fog * vegetation cover * numerical study Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 0.078, year: 2004

  10. Parental verbal abuse and the mediating role of self-criticism in adult internalizing disorders.

    Science.gov (United States)

    Sachs-Ericsson, Natalie; Verona, Edelyn; Joiner, Thomas; Preacher, Kristopher J

    2006-07-01

    Researchers (e.g., [Gibb, B.E., 2002. Childhood maltreatment and negative cognitive styles. A quantitative and qualitative review. Clinical Psychology Review, 22 (2), 223-246]; [Rose, D.T., Abramson, L.Y., 1992. Developmental predictors of depressive cognitive styles: developmental perspectives on depression. In Cicchetti, D., Toth, S.L. (Eds.), Developmental Perspectives on Depression. Rochester symposium on developmental psychopathology, vol. 4, pp. 323-349]) have proposed that when childhood abuse is verbal (rather than sexual or physical), the child is more likely to develop a negative self-schema because the negative self-cognitions are directly supplied to the child by the abuser (e.g., "you are stupid"). In a test of this theory in adult participants, and drawing on the National Comorbidity Survey (NCS) (N=5877), we investigate the mediating role of current levels of self-criticism on the relationship between retrospective reports of parental verbal abuse, as well as sexual and physical abuse, and adult internalizing symptoms. We found self-criticism, but not dependency traits, to fully mediate the relationship between childhood verbal abuse perpetrated by parents and internalizing (depression, anxiety) symptoms. On the other hand, self-criticism was only a partial mediator of the relationship between the other types of abuse and internalizing symptoms. The NCS data is cross-sectional, which limits any firm conclusions regarding causality. While these results are suggestive that self-criticism is a mediator of the relationship between abuse and internalizing symptoms, longitudinal data are necessary to help rule out alternative explanations. Results of this study suggest that childhood abuse experiences, and in particular verbal abuse, may confer risk for internalizing disorders in part because verbal abuse influences the development of a self-critical style.

  11. The critical role of the barrier thickness in spin filter tunneling

    International Nuclear Information System (INIS)

    Miller, Casey W.

    2009-01-01

    Spin filter tunneling is considered in the low bias limit as functions of the temperature dependent barrier parameters. We demonstrate the generation of spin polarized tunneling currents in relation to the magnetic order parameter, and discuss how an interfacially suppressed order parameter leads to a temperature dependent tunneling current asymmetry. Analyzing the full parameter space reveals that the often overlooked barrier thickness plays a critical role in spin filter tunneling. With all else fixed, thicker barriers yield higher spin polarization, and allow a given polarization to be achieved at higher temperatures. This insight may open the door for new materials to serve as spin filter barriers.

  12. Numerical analysis of temperature field improvement with nanoparticles designed to achieve critical power dissipation in magnetic hyperthermia

    Science.gov (United States)

    Tang, Yundong; Flesch, Rodolfo C. C.; Jin, Tao

    2017-07-01

    Magnetic nanoparticle (MNP) hyperthermia is a promising emerging therapy for cancer treatment that is minimally invasive and has been successfully used to treat different types of tumors. The power dissipation of MNPs, which is one of the most important factors during a hyperthermia treatment, is determined by the properties of MNPs and characteristics of the magnetic field. This paper proposes a method based on the finite element analysis for determining the value of the power dissipation of particles (PDP) that can maximize the average temperature of the tumor during treatment and at the same time guarantee that the maximum temperature is within the therapeutic range. The application of the critical PDP value can improve the effectiveness of the treatment since it increases the average temperature in the tumor region while limiting the damage to the healthy tissue that surrounds it. After the critical PDP is determined for a specific model, it is shown how the properties of the MNPs can be chosen to achieve the desired PDP value. The transient behavior of the temperature distribution for two different models considering blood vessels is analyzed as a case study, showing that the presence of a blood vessel inside the tumor region can significantly decrease the uniformity of the temperature field and also increase the treatment duration given its cooling effects. To present a solution that does not depend upon a good model of the tumor region, an alternative method that uses MNPs with low Curie temperature is proposed, given the temperature self-regulating properties of such MNPs. The results demonstrate that the uniformity of the temperature field can be significantly increased by combining the optimization procedure proposed in this paper with the use of low-Curie-temperature MNPs.

  13. Streptavidin-coated gold nanoparticles: critical role of oligonucleotides on stability and fractal aggregation

    Directory of Open Access Journals (Sweden)

    Roberta D'Agata

    2017-01-01

    Full Text Available Gold nanoparticles (AuNPs exhibit unique properties that can be modulated through a tailored surface functionalization, enabling their targeted use in biochemical sensing and medical diagnostics. In particular, streptavidin-modified AuNPs are increasingly used for biosensing purposes. We report here a study of AuNPs surface-functionalized with streptavidin-biotinylated oligonucleotide, focussing on the role played by the oligonucleotide probes in the stabilization/destabilization of the functionalized nanoparticle dispersion. The behaviour of the modified AuNP dispersion as a consequence of the competitive displacement of the biotinylated oligonucleotide has been investigated and the critical role of displaced oligonucletides in triggering the quasi one-dimensional aggregation of nanoparticles is demonstrated for the first time. The thorough understanding of the fundamental properties of bioconjugated AuNPs is of great importance for the design of highly sensitive and reliable functionalized AuNP-based assays.

  14. Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

    Science.gov (United States)

    Zhang, Guoqi; Yang, Li; Kim, Gab Seok; Ryan, Kieran; Lu, Shulin; O'Donnell, Rebekah K; Spokes, Katherine; Shapiro, Nathan; Aird, William C; Kluk, Michael J; Yano, Kiichiro; Sanchez, Teresa

    2013-07-18

    The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 in the regulation of the proadhesion and proinflammatory phenotype of the endothelium. By using genetic approaches and a S1PR2-specific antagonist (JTE013), we found that S1PR2 plays a key role in the permeability and inflammatory responses of the vascular endothelium during endotoxemia. Experiments with bone marrow chimeras (S1pr2(+/+) → S1pr2(+/+), S1pr2(+/+) → S1pr2(-/-), and S1pr2(-/-) → S1pr2(+/+)) indicate the critical role of S1PR2 in the stromal compartment, in the regulation of vascular permeability and vascular inflammation. In vitro, JTE013 potently inhibited tumor necrosis factor α-induced endothelial inflammation. Finally, we provide detailed mechanisms on the downstream signaling of S1PR2 in vascular inflammation that include the activation of the stress-activated protein kinase pathway that, together with the Rho-kinase nuclear factor kappa B pathway (NF-kB), are required for S1PR2-mediated endothelial inflammatory responses. Taken together, our data indicate that S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium and identify S1PR2 as a novel therapeutic target for vascular disorders.

  15. Cross-species epigenetics identifies a critical role for VAV1 in SHH subgroup medulloblastoma maintenance.

    Science.gov (United States)

    Lindsey, J C; Kawauchi, D; Schwalbe, E C; Solecki, D J; Selby, M P; McKinnon, P J; Olson, J M; Hayden, J T; Grundy, R G; Ellison, D W; Williamson, D; Bailey, S; Roussel, M F; Clifford, S C

    2015-09-03

    The identification of key tumorigenic events in Sonic Hedgehog (SHH) subgroup medulloblastomas (MBSHH) will be essential for the development of individualized therapies and improved outcomes. However, beyond confirmation of characteristic SHH pathway mutations, recent genome-wide sequencing studies have not revealed commonly mutated genes with widespread relevance as potential therapeutic targets. We therefore examined any role for epigenetic DNA methylation events in MBSHH using a cross-species approach to candidate identification, prioritization and validation. MBSHH-associated DNA methylation events were first identified in 216 subgrouped human medulloblastomas (50 MBSHH, 28 Wnt/Wingless, 44 Group 3 and 94 Group 4) and their conservation then assessed in tumors arising from four independent murine models of Shh medulloblastoma, alongside any role in tumorigenesis using functional assessments in mouse and human models. This strategy identified widespread regional CpG hypo-methylation of VAV1, leading to its elevated expression, as a conserved aberrant epigenetic event, which characterizes the majority of MBSHH tumors in both species, and is associated with a poor outcome in MBSHH patients. Moreover, direct modulation of VAV1 in mouse and human models revealed a critical role in tumor maintenance, and its abrogation markedly reduced medulloblastoma growth. Further, Vav1 activity regulated granule neuron precursor germinal zone exit and migration initiation in an ex vivo model of early postnatal cerebellar development. These findings establish VAV1 as a critical epigenetically regulated oncogene with a key role in MBSHH maintenance, and highlight its potential as a validated therapeutic target and prognostic biomarker for the improved therapy of medulloblastoma.

  16. The role of the nurse at the end of the life of a critically ill patient.

    Science.gov (United States)

    González-Rincón, M; Díaz de Herrera-Marchal, P; Martínez-Martín, M L

    2018-06-11

    Analyze the role of the nurse at the end of the life of a critically ill patient. Bibliographic review from a search of the health science databases such as PubMed, CINAHL, Cuiden, Scopus, Cochrane, as well as specialized platforms, general and thematic browsers. The limits were language (English or Spanish) and publication date (2005-2015). 180 articles met the inclusion criteria, and 16 of them were selected for analysis. The main results were grouped into three categories of analysis: direct patient care, family-focussed care and the nurse's role within the team. the described roles place the nurse as a key element in humanising death in the ICU and so nurses can and must lead change, playing an active role in creating strategies that really promote the integration of a palliative care approach in ICU. Copyright © 2018 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Numerical investigation of symmetry breaking and critical behavior of the acoustic streaming field in high-intensity discharge lamps

    International Nuclear Information System (INIS)

    Baumann, Bernd; Schwieger, Joerg; Wolff, Marcus; Manders, Freddy; Suijker, Jos

    2015-01-01

    For energy efficiency and material cost reduction it is preferred to drive high-intensity discharge lamps at frequencies of approximately 300 kHz. However, operating lamps at these high frequencies bears the risk of stimulating acoustic resonances inside the arc tube, which can result in low frequency light flicker and even lamp destruction. The acoustic streaming effect has been identified as the link between high frequency resonances and low frequency flicker. A highly coupled three-dimensional multiphysics model has been set up to calculate the acoustic streaming velocity field inside the arc tube of high-intensity discharge lamps. It has been found that the velocity field suffers a phase transition to an asymmetrical state at a critical acoustic streaming force. In certain respects the system behaves similar to a ferromagnet near the Curie point. It is discussed how the model allows to investigate the light flicker phenomenon. Concerning computer resources the procedure is considerably less demanding than a direct approach with a transient model. (paper)

  18. Experimental and numerical determination of critical stress intensity factor of aluminum curved thin sheets under tensile stress

    Energy Technology Data Exchange (ETDEWEB)

    Heidarvand, Majid; Soltani, Naser; Hajializadeh, Farshid [University of Tehran, Tehran (Iran, Islamic Republic of)

    2017-05-15

    We determined the fracture toughness of aluminum curved thin sheets using tensile stress tests and finite element method. We applied Linear elastic fracture mechanics (LEFM) and Feddersen procedure to evaluate stress intensity factor of the samples with central wire-cut cracks and fatigue cracks with different lengths to investigate the notch radius effect. Special fixture design was utilized to establish uniform stress distribution at the crack zone. Less than 9 % difference was found between the wire-cut and the fatigue cracked samples. Since generating central fatigue crack with different lengths required so much effort, wire-cut cracked samples were used to determine critical stress intensity factor. Finite element analysis was also performed on one-quarter of the specimen using both the singular Borsum elements and the regular isoparametric elements to further investigate fracture toughness of the samples. It was observed that the singular elements presented better results than the isoparametric ones. A slight difference was also found between the results obtained from finite element method using singular elements and the experimental results.

  19. Complementary role of critical integral experiment and power reactor start-up experiments for LMFBR neutronics data and method validation

    International Nuclear Information System (INIS)

    Salvatores, M.

    1986-09-01

    Both critical experiments and power reactor results play at present a complementary role in reducing the uncertainties in Key design parameters for LMFBR, which can be relevant for the economic performances of this type of reactors

  20. Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems

    Directory of Open Access Journals (Sweden)

    Sung Ryul Lee

    2018-01-01

    Full Text Available Zinc is recognized as an essential trace metal required for human health; its deficiency is strongly associated with neuronal and immune system defects. Although zinc is a redox-inert metal, it functions as an antioxidant through the catalytic action of copper/zinc-superoxide dismutase, stabilization of membrane structure, protection of the protein sulfhydryl groups, and upregulation of the expression of metallothionein, which possesses a metal-binding capacity and also exhibits antioxidant functions. In addition, zinc suppresses anti-inflammatory responses that would otherwise augment oxidative stress. The actions of zinc are not straightforward owing to its numerous roles in biological systems. It has been shown that zinc deficiency and zinc excess cause cellular oxidative stress. To gain insights into the dual action of zinc, as either an antioxidant or a prooxidant, and the conditions under which each role is performed, the oxidative stresses that occur in zinc deficiency and zinc overload in conjunction with the intracellular regulation of free zinc are summarized. Additionally, the regulatory role of zinc in mitochondrial homeostasis and its impact on oxidative stress are briefly addressed.

  1. An Emerging New Paradigm in Opioid Withdrawal: A Critical Role for Glia-Neuron Signaling in the Periaqueductal Gray

    Directory of Open Access Journals (Sweden)

    Handong Ouyang

    2012-01-01

    Full Text Available The chronic use of opiates (i.e., narcotics such as the natural derivatives of opium including morphine or codeine or opioids (i.e., semisynthetic derivatives of opium and other molecules that activate opioid receptors induces dependence, which is associated with various specific behavioral and somatic signs after their withdrawal or after the administration of an opioid antagonist. Among the brain regions implicated in opiate dependence and withdrawal, the periaqueductal gray area (PAG appears to be critical in regulating the complex signs and symptoms of opioid withdrawal. Numerous neurochemical mechanisms in the PAG have been identified that may contribute to the opioid withdrawal syndrome. Accumulating evidence suggests that glial activation leading to the release of proinflammatory molecules acting on neurons is important in the complex syndrome of opioid dependence and withdrawal. This paper focuses on the recent advances in our understanding of the vital role that glia-neuron interactions play in opioid dependence and withdrawal within the PAG. We summarize those neurochemical mechanisms associated with opioid withdrawal including the recently defined importance of TNFα release from activated glial cells that communicate with TNF receptors on PAG neurons.

  2. Numerical models and their role in emergency response: a perspective on dispersion modeling for emergency preparedness

    International Nuclear Information System (INIS)

    Greenly, G.D.; Dickerson, M.H.

    1983-03-01

    Numerical models on several levels of complexity should be available to the emergency response planner. They are a basic tool but must be used in conjunction with both measurements and experience. When these tools are used in a complimentary fashion they greatly enhance the capability of the consequence manager to respond in an emergency situation. Because each accident or incident develops it's own characteristics and requirements the system must be capable of a flexible response. Interaction and feedback between model results from a suite of models and measurements (including airborne measurements) serve the emergency response planner's spectrum of needs, ranging from planning exercises and emergency precalculations to a real-time emergency response

  3. Critical role of neuropeptides B/W receptor 1 signaling in social behavior and fear memory.

    Directory of Open Access Journals (Sweden)

    Ruby Nagata-Kuroiwa

    Full Text Available Neuropeptide B/W receptor 1 (NPBWR1 is a G-protein coupled receptor, which was initially reported as an orphan receptor, and whose ligands were identified by this and other groups in 2002 and 2003. To examine the physiological roles of NPBWR1, we examined phenotype of Npbwr1⁻/⁻ mice. When presented with an intruder mouse, Npbwr1⁻/⁻ mice showed impulsive contact with the strange mice, produced more intense approaches toward them, and had longer contact and chasing time along with greater and sustained elevation of heart rate and blood pressure compared to wild type mice. Npbwr1⁻/⁻ mice also showed increased autonomic and neuroendocrine responses to physical stress, suggesting that impairment of NPBWR1 leads to stress vulnerability. We also observed that these mice show abnormality in the contextual fear conditioning test. These data suggest that NPBWR1 plays a critical role in limbic system function and stress responses. Histological and electrophysiological studies showed that NPBWR1 acts as an inhibitory regulator on a subpopulation of GABAergic neurons in the lateral division of the CeA and terminates stress responses. These findings suggest important roles of NPBWR1 in regulating amygdala function during physical and social stress.

  4. The role of intergenerational similarity and parenting in adolescent self-criticism: An actor-partner interdependence model.

    Science.gov (United States)

    Bleys, Dries; Soenens, Bart; Boone, Liesbet; Claes, Stephan; Vliegen, Nicole; Luyten, Patrick

    2016-06-01

    Research investigating the development of adolescent self-criticism has typically focused on the role of either parental self-criticism or parenting. This study used an actor-partner interdependence model to examine an integrated theoretical model in which achievement-oriented psychological control has an intervening role in the relation between parental and adolescent self-criticism. Additionally, the relative contribution of both parents and the moderating role of adolescent gender were examined. Participants were 284 adolescents (M = 14 years, range = 12-16 years) and their parents (M = 46 years, range = 32-63 years). Results showed that only maternal self-criticism was directly related to adolescent self-criticism. However, both parents' achievement-oriented psychological control had an intervening role in the relation between parent and adolescent self-criticism in both boys and girls. Moreover, one parent's achievement-oriented psychological control was not predicted by the self-criticism of the other parent. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  5. Childhood Maltreatment, Depressive Symptoms, and Body Dissatisfaction in Patients with Binge Eating Disorder: The Mediating Role of Self-Criticism

    Science.gov (United States)

    Dunkley, David M.; Masheb, Robin M.; Grilo, Carlos M.

    2010-01-01

    Objective We examined the mediating role of self-criticism in the relation between childhood maltreatment and both depressive symptoms and body dissatisfaction in patients with binge eating disorder (BED). Method Participants were 170 BED patients who completed measures of childhood maltreatment, self-criticism, self-esteem, depressive symptoms, and body dissatisfaction. Results Specific forms of childhood maltreatment (emotional abuse, sexual abuse) were significantly associated with body dissatisfaction. Path analyses demonstrated that self-criticism fully mediated the relation between emotional abuse and both depressive symptoms and body dissatisfaction. Specificity for the mediating role of self-criticism was demonstrated in comparison to other potential mediators (low self-esteem) and alternative competing mediation models. Conclusion These results highlight self-criticism as a potential mechanism through which certain forms of childhood maltreatment may be associated with depressive symptoms and body dissatisfaction in BED patients. PMID:20119938

  6. Critical role of nucleotide-binding oligomerization domain-like receptor 3 in vascular repair

    Energy Technology Data Exchange (ETDEWEB)

    Schlaweck, Sebastian; Zimmer, Sebastian; Struck, Rafael [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Bartok, Eva [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Bauernfeind, Franz [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Latz, Eicke [Institute of Innate Immunity, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Hornung, Veit [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Ghanem, Alexander, E-mail: ghanem@uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

    2011-08-05

    Highlights: {yields} NLRP3 is not required for systemic cardiovascular function in healthy mice. {yields} NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and that it does not alter peripheral differential blood counts. {yields} NLRP3 is critical in neointima formation following vascular injury. -- Abstract: Vascular remodeling characterized by hyperproliferative neointima formation is an unfavorable repair process that is triggered by vascular damage. This process is characterized by an increased local inflammatory and proliferative response that critically involves the pro-inflammatory cytokine interleukin-1{beta} (IL-1{beta}). IL-1{beta} is expressed and cytosolically retained as a procytokine that requires additional processing prior to exerting its pro-inflammatory function. Maturation and release of pro IL-1{beta} is governed by a cytosolic protein scaffold that is known as the inflammasome. Here we show that NLRP3 (NOD-like receptor family, pryin domain containing 3), an important activating component of the inflammasome, is involved in neointima formation after vascular injury. NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and does not alter peripheral differential blood counts. However, neointima development following wire injury of the carotid artery was significantly decreased in NLRP3-deficient mice as compared to wild-type controls. In all, NLRP3 plays a non-redundant role in vascular damage mediated neointima formation. Our data establish NLRP3 as a key player in the response to vascular damage, which could open new avenues to therapeutic intervention.

  7. Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice ▿

    Science.gov (United States)

    Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

    2010-01-01

    Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

  8. Critical role of nucleotide-binding oligomerization domain-like receptor 3 in vascular repair

    International Nuclear Information System (INIS)

    Schlaweck, Sebastian; Zimmer, Sebastian; Struck, Rafael; Bartok, Eva; Werner, Nikos; Bauernfeind, Franz; Latz, Eicke; Nickenig, Georg; Hornung, Veit; Ghanem, Alexander

    2011-01-01

    Highlights: → NLRP3 is not required for systemic cardiovascular function in healthy mice. → NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and that it does not alter peripheral differential blood counts. → NLRP3 is critical in neointima formation following vascular injury. -- Abstract: Vascular remodeling characterized by hyperproliferative neointima formation is an unfavorable repair process that is triggered by vascular damage. This process is characterized by an increased local inflammatory and proliferative response that critically involves the pro-inflammatory cytokine interleukin-1β (IL-1β). IL-1β is expressed and cytosolically retained as a procytokine that requires additional processing prior to exerting its pro-inflammatory function. Maturation and release of pro IL-1β is governed by a cytosolic protein scaffold that is known as the inflammasome. Here we show that NLRP3 (NOD-like receptor family, pryin domain containing 3), an important activating component of the inflammasome, is involved in neointima formation after vascular injury. NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and does not alter peripheral differential blood counts. However, neointima development following wire injury of the carotid artery was significantly decreased in NLRP3-deficient mice as compared to wild-type controls. In all, NLRP3 plays a non-redundant role in vascular damage mediated neointima formation. Our data establish NLRP3 as a key player in the response to vascular damage, which could open new avenues to therapeutic intervention.

  9. Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection.

    Directory of Open Access Journals (Sweden)

    Alan C-Y Hsu

    Full Text Available Innate antiviral responses in bronchial epithelial cells (BECs provide the first line of defense against respiratory viral infection and the effectiveness of this response is critically dependent on the type I interferons (IFNs. However the importance of the antiviral responses in BECs during influenza infection is not well understood. We profiled the innate immune response to infection with H3N2 and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway cells. The susceptibility of BECs to influenza infection was not solely dependent on the sialic acid-bearing glycoprotein, and antiviral responses that occurred after viral endocytosis was more important in limiting viral replication. The early antiviral response and apoptosis correlated with the ability to limit viral replication. Both viruses reduced RIG-I associated antiviral responses and subsequent induction of IFN-β. However it was found that there was constitutive release of IFN-β by BECs and this was critical in inducing late antiviral signaling via type I IFN receptors, and was crucial in limiting viral infection. This study characterizes anti-influenza virus responses in airway epithelial cells and shows that constitutive IFN-β release plays a more important role in initiating protective late IFN-stimulated responses during human influenza infection in bronchial epithelial cells.

  10. Assessing the scholar CanMEDS role in residents using critical appraisal techniques

    Directory of Open Access Journals (Sweden)

    Aliya Kassam

    2013-03-01

    Full Text Available Background: In this brief report, we describe two ways in which we assessed the Scholar CanMEDS role using a method to measure residents’ ability to complete a critical appraisal.  These were incorporated into a modified OSCE format where two stations consisted of 1 critically appraising an article and 2 critiquing an abstract. Method: Residents were invited to participate in the CanMEDS In-Training Exam (CITE through the Office of Postgraduate Medical Education. Mean scores for the two Scholar stations were calculated using the number of correct responses out of 10. The global score represented the examiner’s overall impression of the resident’s knowledge and effort.  Correlations between scores are also presented between the two Scholar stations and a paired sample t-test comparing the global mean scores of the two stations was also performed. Results: Sixty-three of the 64 residents registered to complete the CanMEDS In-Training Exam including the two Scholar stations.  There were no significant differences between the global scores of the Scholar stations showing that the overall knowledge and effort of the residents was similar across both stations (3.8 vs. 3.5, p = 0.13.  The correlation between the total mean scores of both stations (inter-station reliability was also non-significant (r = 0.05, p = 0.67.  No significant differences between senior residents and junior residents were detected or between internal medicine residents and non-internal medicine residents. Conclusion: Further testing of these stations is needed and other novel ways of assessing the Scholar role competencies should also be investigated.

  11. Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function

    Science.gov (United States)

    Kara, Firas M.; Chitu, Violeta; Sloane, Jennifer; Axelrod, Matthew; Fredholm, Bertil B.; Stanley, E. Richard; Cronstein, Bruce N.

    2010-01-01

    Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A1R, A2AR, A2BR, and A3R). Because A1R occupancy promotes fusion of human monocytes to form giant cells in vitro, we determined whether A1R occupancy similarly promotes osteoclast function and formation. Bone marrow cells (BMCs) were harvested from C57Bl/6 female mice or A1R-knockout mice and their wild-type (WT) littermates and differentiated into osteoclasts in the presence of colony stimulating factor-1 and receptor activator of NF-κB ligand in the presence or absence of the A1R antagonist 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX). Osteoclast morphology was analyzed in tartrate-resistant acid phosphatase or F-actin-stained samples, and bone resorption was evaluated by toluidine blue staining of dentin. BMCs from A1R-knockout mice form fewer osteoclasts than BMCs from WT mice, and the A1R antagonist DPCPX inhibits osteoclast formation (IC50=1 nM), with altered morphology and reduced ability to resorb bone. A1R blockade increased ubiquitination and degradation of TRAF6 in RAW264.7 cells induced to differentiate into osteoclasts. These studies suggest a critical role for adenosine in bone homeostasis via interaction with adenosine A1R and further suggest that A1R may be a novel pharmacologic target to prevent the bone loss associated with inflammatory diseases and menopause.—Kara, F. M., Chitu, V., Sloane, J., Axelrod, M., Fredholm, B. B., Stanley, R., Cronstein, B. N. Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function. PMID:20181934

  12. Examining the role of dissolved organic nitrogen in stream ecosystems across biomes and Critical Zone gradients

    Science.gov (United States)

    Wymore, A.; Rodriguez-Cardona, B.; Coble, A. A.; Potter, J.; Lopez Lloreda, C.; Perez Rivera, K.; De Jesus Roman, A.; Bernal, S.; Martí Roca, E.; Kram, P.; Hruska, J.; Prokishkin, A. S.; McDowell, W. H.

    2016-12-01

    Watershed nitrogen exports are often dominated by dissolved organic nitrogen (DON); yet, little is known about the role ambient DON plays in ecosystems. As an organic nutrient, DON may serve as either an energy source or as a nutrient source. One hypothesized control on DON is nitrate (NO3-) availability. Here we examine the interaction of NO3- and DON in streams across temperate forests, tropical rainforests, and Mediterranean and taiga biomes. Experimental streams also drain contrasting Critical Zones which provide gradients of vegetation, soil type and lithology (e.g. volcaniclastic, granitic, ultramafic, Siberian Traps Flood Basalt) in which to explore how the architecture of the Critical Zone affects microbial biogeochemical reactions. Streams ranged in background dissolved organic carbon (DOC) concentration (1-50 mg C/L) and DOC: NO3- ratios (10-2000). We performed a series of ecosystem-scale NO3- additions in multiple streams within each environment and measured the change in DON concentration. Results demonstrate that there is considerable temporal and spatial variation across systems with DON both increasing and decreasing in response to NO3- addition. Ecologically this suggests that DON can serve as both a nutrient source and an energy source to aquatic microbial communities. In contrast, DOC concentrations rarely changed in response to NO3- additions suggesting that the N-rich fraction of the ambient dissolved organic matter pool is more bioreactive than the C-rich fraction. Contrasting responses of the DON and DOC pools indicate different mechanisms controlling their respective cycling. It is likely that DON plays a larger role in ecosystems than previously recognized.

  13. Role of beliefs and emotions in numerical problem solving in university physics education

    Science.gov (United States)

    Bodin, Madelen; Winberg, Mikael

    2012-06-01

    Numerical problem solving in classical mechanics in university physics education offers a learning situation where students have many possibilities of control and creativity. In this study, expertlike beliefs about physics and learning physics together with prior knowledge were the most important predictors of the quality of performance of a task with many degrees of freedom. Feelings corresponding to control and concentration, i.e., emotions that are expected to trigger students’ intrinsic motivation, were also important in predicting performance. Unexpectedly, intrinsic motivation, as indicated by enjoyment and interest, together with students’ personal interest and utility value beliefs did not predict performance. This indicates that although a certain degree of enjoyment is probably necessary, motivated behavior is rather regulated by integration and identification of expertlike beliefs about learning and are more strongly associated with concentration and control during learning and, ultimately, with high performance. The results suggest that the development of students’ epistemological beliefs is important for students’ ability to learn from realistic problem-solving situations with many degrees of freedom in physics education.

  14. The role of numerical simulation for the development of an advanced HIFU system

    Science.gov (United States)

    Okita, Kohei; Narumi, Ryuta; Azuma, Takashi; Takagi, Shu; Matumoto, Yoichiro

    2014-10-01

    High-intensity focused ultrasound (HIFU) has been used clinically and is under clinical trials to treat various diseases. An advanced HIFU system employs ultrasound techniques for guidance during HIFU treatment instead of magnetic resonance imaging in current HIFU systems. A HIFU beam imaging for monitoring the HIFU beam and a localized motion imaging for treatment validation of tissue are introduced briefly as the real-time ultrasound monitoring techniques. Numerical simulations have a great impact on the development of real-time ultrasound monitoring as well as the improvement of the safety and efficacy of treatment in advanced HIFU systems. A HIFU simulator was developed to reproduce ultrasound propagation through the body in consideration of the elasticity of tissue, and was validated by comparison with in vitro experiments in which the ultrasound emitted from the phased-array transducer propagates through the acrylic plate acting as a bone phantom. As the result, the defocus and distortion of the ultrasound propagating through the acrylic plate in the simulation quantitatively agree with that in the experimental results. Therefore, the HIFU simulator accurately reproduces the ultrasound propagation through the medium whose shape and physical properties are well known. In addition, it is experimentally confirmed that simulation-assisted focus control of the phased-array transducer enables efficient assignment of the focus to the target. Simulation-assisted focus control can contribute to design of transducers and treatment planning.

  15. Role of beliefs and emotions in numerical problem solving in university physics education

    Directory of Open Access Journals (Sweden)

    Madelen Bodin

    2012-02-01

    Full Text Available Numerical problem solving in classical mechanics in university physics education offers a learning situation where students have many possibilities of control and creativity. In this study, expertlike beliefs about physics and learning physics together with prior knowledge were the most important predictors of the quality of performance of a task with many degrees of freedom. Feelings corresponding to control and concentration, i.e., emotions that are expected to trigger students’ intrinsic motivation, were also important in predicting performance. Unexpectedly, intrinsic motivation, as indicated by enjoyment and interest, together with students’ personal interest and utility value beliefs did not predict performance. This indicates that although a certain degree of enjoyment is probably necessary, motivated behavior is rather regulated by integration and identification of expertlike beliefs about learning and are more strongly associated with concentration and control during learning and, ultimately, with high performance. The results suggest that the development of students’ epistemological beliefs is important for students’ ability to learn from realistic problem-solving situations with many degrees of freedom in physics education.

  16. Politics of Ebola and the critical role of global health diplomacy for the CARICOM

    Directory of Open Access Journals (Sweden)

    Vijay Kumar Chattu

    2017-01-01

    Full Text Available The 2014 Ebola epidemic was the largest in history, affecting Guinea, Liberia, Sierra Leone, Nigeria, and Mali in West Africa. The International Health Regulations are legally binding in 194 countries including all the member states of WHO “to prevent, protect against, control, and provide a public health response to the international spread of disease.” Since the Caribbean Community region heavily depends on tourism, a single case of the disease anywhere in the region could have serious negative consequences for the rest of the region's tourism industry. Global health diplomacy brings together the disciplines of public health, international affairs, management, law, and economics and focuses on negotiations that shape and manage the global policy environment for health. The regional institutes such as Caribbean Public Health Agency should play a more proactive and pivotal role in the creation of regional response teams in all the island nations collaborating with the departments of public health and epidemiology at the regional campuses of The University of the West Indies. The role of global health diplomacy and its practice should be encouraged to reach a consensus among the stakeholders considering the threat to the health security in the region. There is a need for the cadre of global health diplomats who has a critical understanding of health and also the practice of diplomacy since such serious health issues have implications at the global level in this globalized world.

  17. A critical role for the chimpanzee model in the study of hepatitis C.

    Science.gov (United States)

    Bukh, Jens

    2004-06-01

    Chimpanzees remain the only recognized animal model for the study of hepatitis C virus (HCV). Studies performed in chimpanzees played a critical role in the discovery of HCV and are continuing to play an essential role in defining the natural history of this important human pathogen. In the absence of a reproducible cell culture system, the infectivity titer of HCV challenge pools can be determined only in chimpanzees. Recent studies in chimpanzees have provided new insight into the nature of host immune responses-particularly the intrahepatic responses-following primary and secondary experimental HCV infections. The immunogenicity and efficacy of vaccine candidates against HCV can be tested only in chimpanzees. Finally, it would not have been possible to demonstrate the infectivity of infectious clones of HCV without chimpanzees. Chimpanzees became infected when RNA transcripts from molecular clones were inoculated directly into the liver. The infection generated by such transfection did not differ significantly from that observed in animals infected intravenously with wild-type HCV. The RNA inoculated into chimpanzees originated from a single sequence, and the animals therefore had a monoclonal HCV infection. Monoclonal infection simplifies studies of HCV, because virus interaction with the host is not confounded by the quasispecies invariably present in a natural infection. It furthermore permits true homologous challenge in studies of protective immunity and in testing the efficacy of vaccine candidates. Finally, this in vivo transfection system has made it possible to test for the first time the importance of genetic elements for HCV infectivity.

  18. Memory Erasure Experiments Indicate a Critical Role of CaMKII in Memory Storage.

    Science.gov (United States)

    Rossetti, Tom; Banerjee, Somdeb; Kim, Chris; Leubner, Megan; Lamar, Casey; Gupta, Pooja; Lee, Bomsol; Neve, Rachael; Lisman, John

    2017-09-27

    The abundant synaptic protein CaMKII is necessary for long-term potentiation (LTP) and memory. However, whether CaMKII is required only during initial processes or whether it also mediates memory storage remains unclear. The most direct test of a storage role is the erasure test. In this test, a putative memory molecule is inhibited after learning. The key prediction is that this should produce persistent memory erasure even after the inhibitory agent is removed. We conducted this test using transient viral (HSV) expression of dominant-negative CaMKII-alpha (K42M) in the hippocampus. This produced persistent erasure of conditioned place avoidance. As an additional test, we found that expression of activated CaMKII (T286D/T305A/T306A) impaired place avoidance, a result not expected if a process other than CaMKII stores memory. Our behavioral results, taken together with prior experiments on LTP, strongly support a critical role of CaMKII in LTP maintenance and memory storage. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Value congruence and depressive symptoms among critical care clinicians: The mediating role of moral distress.

    Science.gov (United States)

    Lamiani, Giulia; Dordoni, Paola; Argentero, Piergiorgio

    2018-02-01

    Clinicians working in intensive care units are often exposed to several job stressors that can negatively affect their mental health. Literature has acknowledged the role of value congruence and job control in determining clinicians' psychological well-being and depressive symptoms. However, potential mediators of this association have been scarcely examined. This study aimed to test the mediating role of moral distress in the relationship between value congruence and job control, on the one hand, and depression, on the other hand. A cross-sectional study involving physicians, nurses, and residents working in 7 intensive care units in the north of Italy was conducted. Clinicians were administered in the Italian Moral Distress Scale-Revised, the value and control subscales of the Areas of Worklife Scale, and the Beck Depression Inventory II. Structural equation modeling was used to test the mediation model. Analysis on 170 questionnaires (response rate 72%) found no relations between job control and moral distress. A total indirect effect of value congruence on depression through moral distress (β = -.12; p = .02) was found. Moral distress contributes to the development of depressive symptoms among critical care clinicians who perceive a value incongruence with their organization and therefore should be addressed. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Cutting edge: A critical functional role for IL-23 in psoriasis.

    Science.gov (United States)

    Tonel, Giulia; Conrad, Curdin; Laggner, Ute; Di Meglio, Paola; Grys, Katarzyna; McClanahan, Terrill K; Blumenschein, Wendy M; Qin, Jian-Zhong; Xin, Hong; Oldham, Elizabeth; Kastelein, Robert; Nickoloff, Brian J; Nestle, Frank O

    2010-11-15

    Interleukin-23 is a key cytokine involved in the generation of Th17 effector cells. Clinical efficacy of an anti-p40 mAb blocking both IL-12 and IL-23 and disease association with single nucleotide polymorphisms in the IL23R gene raise the question of a functional role of IL-23 in psoriasis. In this study, we provide a comprehensive analysis of IL-23 and its receptor in psoriasis and demonstrate its functional importance in a disease-relevant model system. The expression of IL-23 and its receptor was increased in the tissues of patients with psoriasis. Injection of a mAb specifically neutralizing human IL-23 showed IL-23-dependent inhibition of psoriasis development comparable to the use of anti-TNF blockers in a clinically relevant xenotransplant mouse model of psoriasis. Together, our results identify a critical functional role for IL-23 in psoriasis and provide the rationale for new treatment strategies in chronic epithelial inflammatory disorders.

  1. C-terminus glycans with critical functional role in the maturation of secretory glycoproteins.

    Directory of Open Access Journals (Sweden)

    Daniela Cioaca

    Full Text Available The N-glycans of membrane glycoproteins are mainly exposed to the extracellular space. Human tyrosinase is a transmembrane glycoprotein with six or seven bulky N-glycans exposed towards the lumen of subcellular organelles. The central active site region of human tyrosinase is modeled here within less than 2.5 Å accuracy starting from Streptomyces castaneoglobisporus tyrosinase. The model accounts for the last five C-terminus glycosylation sites of which four are occupied and indicates that these cluster in two pairs--one in close vicinity to the active site and the other on the opposite side. We have analyzed and compared the roles of all tyrosinase N-glycans during tyrosinase processing with a special focus on the proximal to the active site N-glycans, s6:N337 and s7:N371, versus s3:N161 and s4:N230 which decorate the opposite side of the domain. To this end, we have constructed mutants of human tyrosinase in which its seven N-glycosylation sites were deleted. Ablation of the s6:N337 and s7:N371 sites arrests the post-translational productive folding process resulting in terminally misfolded mutants subjected to degradation through the mannosidase driven ERAD pathway. In contrast, single mutants of the other five N-glycans located either opposite to the active site or into the N-terminus Cys1 extension of tyrosinase are temperature-sensitive mutants and recover enzymatic activity at the permissive temperature of 31°C. Sites s3 and s4 display selective calreticulin binding properties. The C-terminus sites s7 and s6 are critical for the endoplasmic reticulum retention and intracellular disposal. Results herein suggest that individual N-glycan location is critical for the stability, regional folding control and secretion of human tyrosinase and explains some tyrosinase gene missense mutations associated with oculocutaneous albinism type I.

  2. A critical role for Arabidopsis MILDEW RESISTANCE LOCUS O2 in systemic acquired resistance.

    Science.gov (United States)

    Gruner, Katrin; Zeier, Tatyana; Aretz, Christina; Zeier, Jürgen

    2018-04-16

    Members of the MILDEW RESISTANCE LOCUS O (MLO) gene family confer susceptibility to powdery mildews in different plant species, and their existence therefore seems to be disadvantageous for the plant. We recognized that expression of the Arabidopsis MLO2 gene is induced after inoculation with the bacterial pathogen Pseudomonas syringae, promoted by salicylic acid (SA) signaling, and systemically enhanced in the foliage of plants exhibiting systemic acquired resistance (SAR). Importantly, distinct mlo2 mutant lines were unable to systemically increase resistance to bacterial infection after inoculation with P. syringae, indicating that the function of MLO2 is necessary for biologically-induced SAR in Arabidopsis. Our data also suggest that the close homolog MLO6 has a supportive but less critical role in SAR. In contrast to SAR, basal resistance to bacterial infection was not affected in mlo2. Remarkably, SAR-defective mlo2 mutants were still competent in systemically increasing the levels of the SAR-activating metabolites pipecolic acid (Pip) and SA after inoculation, and to enhance SAR-related gene expression in distal plant parts. Furthermore, although MLO2 was not required for SA- or Pip-inducible defense gene expression, it was essential for the proper induction of disease resistance by both SAR signals. We conclude that MLO2 acts as a critical downstream component in the execution of SAR to bacterial infection, being required for the translation of elevated defense responses into disease resistance. Moreover, our data suggest a function for MLO2 in the activation of plant defense priming during a P. syringae challenge. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. Mechanotransduction in cortical bone and the role of piezoelectricity: a numerical approach.

    Science.gov (United States)

    Stroe, M C; Crolet, J M; Racila, M

    2013-01-01

    This paper is a contribution to a plausible explanation of the mechanotransduction phenomenon in cortical bone during its remodelling. Our contribution deals only with the mechanical processes and the biological aspects have not been taken into account. It is well known that osteoblasts are able to generate bone in a suitable bony substitute only under fluid action. But the bone created in this manner is not organised to resist specific mechanical stress. Our aim was to suggest the nature of the physical information that can be transmitted - directly or via a biological or biochemical process - to the cell to initiate a cellular activity inducing the reconstruction of the osteon that is best adapted to local mechanical stresses. For this, the cell must have, from our point of view, a good knowledge of its structural environment. But this knowledge exists at the cellular scale while the bone is loaded at the macroscopic scale. This study is based on the SiNuPrOs model that allows exchange of information between the different structural scales of cortical bone. It shows that more than the fluid, the collagen - via its piezoelectric properties - plays an essential role in the transmission of information between the macroscopic and nanoscopic scales. Moreover, this process allows us to explain various dysfunctions and even some diseases.

  4. Alpha-CaMKII plays a critical role in determining the aggressive behavior of human osteosarcoma.

    Science.gov (United States)

    Daft, Paul G; Yuan, Kaiyu; Warram, Jason M; Klein, Michael J; Siegal, Gene P; Zayzafoon, Majd

    2013-04-01

    Osteosarcoma is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in osteosarcoma treatment, more specific molecular targets are needed as potential therapeutic options. One target of interest is α-Ca(2+)/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca(2+)-linked signaling, which has been shown to regulate tumor cell proliferation and differentiation. Here, we investigate the role of α-CaMKII in the growth and tumorigenicity of human osteosarcoma. We show that α-CaMKII is highly expressed in primary osteosarcoma tissue derived from 114 patients, and is expressed in varying levels in different human osteosarcoma (OS) cell lines [MG-63, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)/HOS, and 143B). To examine whether α-CaMKII regulates osteosarcoma tumorigenic properties, we genetically inhibited α-CaMKII in two osteosarcoma cell lines using two different α-CaMKII shRNAs delivered by lentiviral vectors and overexpressed α-CaMKII by retrovirus. The genetic deletion of α-CaMKII by short hairpin RNA (shRNA) in MG-63 and 143B cells resulted in decreased proliferation (50% and 41%), migration (22% and 25%), and invasion (95% and 90%), respectively. The overexpression of α-CaMKII in HOS cells resulted in increased proliferation (240%), migration (640%), and invasion (10,000%). Furthermore, α-CaMKII deletion in MG-63 cells significantly reduced tumor burden in vivo (65%), whereas α-CaMKII overexpression resulted in tumor formation in a previously nontumor forming osteosarcoma cell line (HOS). Our results suggest that α-CaMKII plays a critical role in determining the aggressive phenotype of osteosarcoma, and its inhibition could be an attractive therapeutic target to combat this devastating adolescent disease. ©2013 AACR.

  5. Determining the Role of Hydraulic Redistribution Regimes in the Critical Zone

    Science.gov (United States)

    Lee, E.; Kumar, P.; Barron-Gafford, G.; Scott, R. L.; Hendryx, S.; Sanchez-Canete, E. P.

    2015-12-01

    A primary challenge in critical zone science is to understand and predict the interaction between aboveground and belowground ecohydrologic processes. We study the role of hydraulic redistribution (HR) by roots as a mechanism for facilitating aboveground-belowground interactions that drive water and carbon dynamics and the development of emergent spatial patterns of soil moisture and vegetation distribution. By linking field measurements of stem, taproot, and lateral root sap flux, with a shared resource model where the soil is a common reservoir, we examine competitive and facilitative dependencies between the co-occurring plant species. We used trenching as a means of severing any HR connectivity between overstory and understory plants in a subset of plots. We monitored leaf- level transpiration, photosynthesis, sub-canopy ET, NEE, soil evaporation, and soil respiration for trenched and un-trenched (control) trees in a dryland savanna that lacks access to stable soil moisture sources. HR in the trees at the site is detected, but the implications of HR on overstory-understory interactions and resulting spatial patterns and gradients remain untested. During an inter-storm period of the rainy season, we observed hydraulic lift, which may be increasing water availability to understory. Understory grasses may survive inter-storm dry periods by way of facilitative dependency on water resources supplied by overstory trees. On the other hand, immediately after storms we observe hydraulic descent that may be reducing water availability for the understory. Modeling is incorporated to capture the competitive and facilitative interaction between aboveground and belowground as detected in the field. This study provides deep insights for dryland regions, which enables broader generalizations regarding the interaction between groundwater, vegetation roots and aboveground assemblage and their role in whole-ecosystem performance.

  6. The NLRP3 Inflammasome Has a Critical Role in Peritoneal Dialysis-Related Peritonitis.

    Science.gov (United States)

    Hautem, Nicolas; Morelle, Johann; Sow, Amadou; Corbet, Cyril; Feron, Olivier; Goffin, Eric; Huaux, François; Devuyst, Olivier

    2017-07-01

    Bacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). During peritonitis, the peritoneal membrane undergoes structural and functional alterations that are mediated by IL-1 β The NLRP3 inflammasome is a caspase-1-activating multiprotein complex that links sensing of microbial and stress products to activation of proinflammatory cytokines, including IL-1 β The potential roles of the NLRP3 inflammasome and IL-1 β in the peritoneal membrane during acute peritonitis have not been investigated. Here, we show that the NLRP3 inflammasome is activated during acute bacterial peritonitis in patients on PD, and this activation associates with the release of IL-1 β in the dialysate. In mice, lipopolysaccharide- or Escherichia coli -induced peritonitis led to IL-1 β release in the peritoneal membrane. The genetic deletion of Nalp3 , which encodes NLRP3, abrogated defects in solute transport during acute peritonitis and restored ultrafiltration. In human umbilical vein endothelial cells, IL-1 β treatment directly enhanced endothelial cell proliferation and increased microvascular permeability. These in vitro effects require endothelial IL-1 receptors, shown by immunofluorescence to be expressed in peritoneal capillaries in mice. Furthermore, administration of the IL-1 β receptor antagonist, anakinra, efficiently decreased nitric oxide production and vascular proliferation and restored peritoneal function in mouse models of peritonitis, even in mice treated with standard-of-care antibiotherapy. These data demonstrate that NLRP3 activation and IL-1 β release have a critical role in solute transport defects and tissue remodeling during PD-related peritonitis. Blockade of the NLRP3/IL-1 β axis offers a novel method for rescuing morphologic alterations and transport defects during acute peritonitis. Copyright © 2017 by the American Society of Nephrology.

  7. Cyber Security Insider Threats :: Government’s Role in Protecting India’s Critical Infrastructure Sectors

    OpenAIRE

    Vohra, Pulkit

    2014-01-01

    This research identifies the problem of insider threats in the critical infrastructure sectors of India. It is structured to answer the research question: "Why insider threats should be the primary concern for Indian government to protect its critical infrastructure sectors.” It defines the critical infrastructure sectors and portrays the cyber security scenario of India. Also, through the research study, it identifies the lack of awareness and non-seriousness of employees in the critical sec...

  8. Can We Protect the Gut in Critical Illness: The Role of Growth Factors and Other Novel Approaches

    Science.gov (United States)

    Dominguez, Jessica A.; Coopersmith, Craig M.

    2010-01-01

    Synopsis The intestine plays a central role in the pathophysiology of critical illness and is frequently called the “motor” of the systemic inflammatory response. Perturbations to the intestinal barrier can lead to distant organ damage and multiple organ failure. Therefore, identifying ways to preserve intestinal integrity may be of paramount importance. Growth factors and other peptides have emerged as potential tools for modulation of intestinal inflammation and repair due to their roles in cellular proliferation, differentiation, migration, and survival. In this review, we will examine the involvement of growth factors and other peptides in intestinal epithelial repair during critical illness and their potential use as therapeutic targets. PMID:20643306

  9. Can we protect the gut in critical illness? The role of growth factors and other novel approaches.

    Science.gov (United States)

    Dominguez, Jessica A; Coopersmith, Craig M

    2010-07-01

    The intestine plays a central role in the pathophysiology of critical illness and is frequently called the "motor" of the systemic inflammatory response. Perturbations to the intestinal barrier can lead to distant organ damage and multiple organ failure. Therefore, identifying ways to preserve intestinal integrity may be of paramount importance. Growth factors and other peptides have emerged as potential tools for modulation of intestinal inflammation and repair due to their roles in cellular proliferation, differentiation, migration, and survival. This review examines the involvement of growth factors and other peptides in intestinal epithelial repair during critical illness and their potential use as therapeutic targets. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Critical role of acrolein in secondary injury following ex vivo spinal cord trauma.

    Science.gov (United States)

    Hamann, Kristin; Durkes, Abigail; Ouyang, Hui; Uchida, Koji; Pond, Amber; Shi, Riyi

    2008-11-01

    The pathophysiology of spinal cord injury (SCI) is characterized by the initial, primary injury followed by secondary injury processes in which oxidative stress is a critical component. Secondary injury processes not only exacerbate pathology at the site of primary injury, but also result in spreading of injuries to the adjacent, otherwise healthy tissue. The lipid peroxidation byproduct acrolein has been implicated as one potential mediator of secondary injury. To further and rigorously elucidate the role of acrolein in secondary injury, a unique ex vivo model is utilized to isolate the detrimental effects of mechanical injury from toxins such as acrolein that are produced endogenously following SCI. We demonstrate that (i) acrolein-Lys adducts are capable of diffusing from compressed tissue to adjacent, otherwise uninjured tissue; (ii) secondary injury by itself produces significant membrane damage and increased superoxide production; and (iii) these injuries are significantly attenuated by the acrolein scavenger hydralazine. Furthermore, hydralazine treatment results in significantly less membrane damage 2 h following compression injury, but not immediately after. These findings support our hypothesis that, following SCI, acrolein is increased to pathologic concentrations, contributes significantly to secondary injury, and thus represents a novel target for scavenging to promote improved recovery.

  11. A critical role for noncoding 5S rRNA in regulating Mdmx stability.

    Science.gov (United States)

    Li, Muyang; Gu, Wei

    2011-09-16

    Both p53 and Mdmx are ubiquitinated and degraded by the same E3 ligase Mdm2; interestingly, however, while p53 is rapidly degraded by Mdm2, Mdmx is a stable protein in most cancer cells. Thus, the mechanism by which Mdmx is degraded by Mdm2 needs further elucidation. Here, we identified the noncoding 5S rRNA as a major component of Mdmx-associated complexes from human cells. We show that 5S rRNA acts as a natural inhibitor of Mdmx degradation by Mdm2. RNAi-mediated knockdown of endogenous 5S rRNA, while not affecting p53 levels, significantly induces Mdmx degradation and, subsequently, activates p53-dependent growth arrest. Notably, 5S rRNA binds the RING domain of Mdmx and blocks its ubiquitination by Mdm2, whereas Mdm2-mediated p53 ubiquitination remains intact. These results provide insights into the differential effects on p53 and Mdmx by Mdm2 in vivo and reveal a critical role for noncoding 5S rRNA in modulating the p53-Mdmx axis. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Critical Role of Monoclinic Polarization Rotation in High-Performance Perovskite Piezoelectric Materials.

    Science.gov (United States)

    Liu, Hui; Chen, Jun; Fan, Longlong; Ren, Yang; Pan, Zhao; Lalitha, K V; Rödel, Jürgen; Xing, Xianran

    2017-07-07

    High-performance piezoelectric materials constantly attract interest for both technological applications and fundamental research. The understanding of the origin of the high-performance piezoelectric property remains a challenge mainly due to the lack of direct experimental evidence. We perform in situ high-energy x-ray diffraction combined with 2D geometry scattering technology to reveal the underlying mechanism for the perovskite-type lead-based high-performance piezoelectric materials. The direct structural evidence reveals that the electric-field-driven continuous polarization rotation within the monoclinic plane plays a critical role to achieve the giant piezoelectric response. An intrinsic relationship between the crystal structure and piezoelectric performance in perovskite ferroelectrics has been established: A strong tendency of electric-field-driven polarization rotation generates peak piezoelectric performance and vice versa. Furthermore, the monoclinic M_{A} structure is the key feature to superior piezoelectric properties as compared to other structures such as monoclinic M_{B}, rhombohedral, and tetragonal. A high piezoelectric response originates from intrinsic lattice strain, but little from extrinsic domain switching. The present results will facilitate designing high-performance perovskite piezoelectric materials by enhancing the intrinsic lattice contribution with easy and continuous polarization rotation.

  13. Genesis of the "Critical-Acceleration of MOND" and Its Role in "Formation of Structures"

    Directory of Open Access Journals (Sweden)

    Tank H. K.

    2012-10-01

    Full Text Available As an attempt to explain the “flattening of galaxies rotation-curves”, Milgrom proposed a Modification of Newtonian Dynamics MOND, in which he needed a new constant of nature a 0 , termed as “critical-acceleration-of MOND”, in his best-fit empirical formula. But so far it has been an ad-hoc introduction of a new constant. Whereas this article pro- poses: (i a genesis of this constant; (ii explains its recurrences in various physical sit- uations; and (iii its role in determining the size and radii of various structures, like: the electron, the proton, the nucleus-of-atom, the globular-clusters, the spiral-galaxies, the galactic-clusters and the whole universe. In this process we get a new interpretation of “the cosmological-red-shift”, that the linear part of the cosmological-red-shift may not be due to “metric-expansion-of-space”; and even the currently-believed “accelerated- expansion” may be slowing down with time.

  14. Developmental Ethanol Exposure Causes Reduced Feeding and Reveals a Critical Role for Neuropeptide F in Survival

    Science.gov (United States)

    Guevara, Amanda; Gates, Hillary; Urbina, Brianna; French, Rachael

    2018-01-01

    Food intake is necessary for survival, and natural reward circuitry has evolved to help ensure that animals ingest sufficient food to maintain development, growth, and survival. Drugs of abuse, including alcohol, co-opt the natural reward circuitry in the brain, and this is a major factor in the reinforcement of drug behaviors leading to addiction. At the junction of these two aspects of reward are alterations in feeding behavior due to alcohol consumption. In particular, developmental alcohol exposure (DAE) results in a collection of physical and neurobehavioral disorders collectively referred to as Fetal Alcohol Spectrum Disorder (FASD). The deleterious effects of DAE include intellectual disabilities and other neurobehavioral changes, including altered feeding behaviors. Here we use Drosophila melanogaster as a genetic model organism to study the effects of DAE on feeding behavior and the expression and function of Neuropeptide F. We show that addition of a defined concentration of ethanol to food leads to reduced feeding at all stages of development. Further, genetic conditions that reduce or eliminate NPF signaling combine with ethanol exposure to further reduce feeding, and the distribution of NPF is altered in the brains of ethanol-supplemented larvae. Most strikingly, we find that the vast majority of flies with a null mutation in the NPF receptor die early in larval development when reared in ethanol, and provide evidence that this lethality is due to voluntary starvation. Collectively, we find a critical role for NPF signaling in protecting against altered feeding behavior induced by developmental ethanol exposure. PMID:29623043

  15. A critical role of the human hippocampus in an electrophysiological measure of implicit memory

    Science.gov (United States)

    Addante, Richard James

    2015-01-01

    The hippocampus has traditionally been thought to be critical for conscious explicit memory but not necessary for unconscious implicit memory processing. In a recent study of a group of mild amnesia patients with evidence of MTL damage limited to the hippocampus, subjects were tested on a direct test of item recognition confidence while electroencephalogram (EEG) was acquired, and revealed intact measures of explicit memory from 400–600ms (mid-frontal old-new effect, FN400). The current investigation re-analyzed this data to study event-related potentials (ERPs) of implicit memory, using a recently developed procedure that eliminated declarative memory differences. Prior ERP findings from this technique were first replicated in two independent matched control groups, which exhibited reliable implicit memory effects in posterior scalp regions from 400–600 msec, which were topographically dissociated from the explicit memory effects of familiarity. However, patients were found to be dramatically impaired in implicit memory effects relative to control subjects, as quantified by a reliable condition × group interaction. Several control analysis were conducted to consider alternative factors that could account for the results, including outliers, sample size, age, or contamination by explicit memory, and each of these factors were systematically ruled out. Results suggest that the hippocampus plays a fundamental role in aspects of memory processing that is beyond conscious awareness. The current findings therefore indicate that both memory systems of implicit and explicit memory may rely upon the same neural structures – but function in different physiological ways. PMID:25562828

  16. The critical role of extreme heat for maize production in the United States

    Science.gov (United States)

    Lobell, David B.; Hammer, Graeme L.; McLean, Greg; Messina, Carlos; Roberts, Michael J.; Schlenker, Wolfram

    2013-05-01

    Statistical studies of rainfed maize yields in the United States and elsewhere have indicated two clear features: a strong negative yield response to accumulation of temperatures above 30°C (or extreme degree days (EDD)), and a relatively weak response to seasonal rainfall. Here we show that the process-based Agricultural Production Systems Simulator (APSIM) is able to reproduce both of these relationships in the Midwestern United States and provide insight into underlying mechanisms. The predominant effects of EDD in APSIM are associated with increased vapour pressure deficit, which contributes to water stress in two ways: by increasing demand for soil water to sustain a given rate of carbon assimilation, and by reducing future supply of soil water by raising transpiration rates. APSIM computes daily water stress as the ratio of water supply to demand, and during the critical month of July this ratio is three times more responsive to 2°C warming than to a 20% precipitation reduction. The results suggest a relatively minor role for direct heat stress on reproductive organs at present temperatures in this region. Effects of elevated CO2 on transpiration efficiency should reduce yield sensitivity to EDD in the coming decades, but at most by 25%.

  17. Critical role for BIM in T cell receptor restimulation-induced death

    Directory of Open Access Journals (Sweden)

    Fleisher Thomas A

    2008-08-01

    Full Text Available Abstract Background Upon repeated or chronic antigen stimulation, activated T cells undergo a T cell receptor (TCR-triggered propriocidal cell death important for governing the intensity of immune responses. This is thought to be chiefly mediated by an extrinsic signal through the Fas-FasL pathway. However, we observed that TCR restimulation still potently induced apoptosis when this interaction was blocked, or genetically impaired in T cells derived from autoimmune lymphoproliferative syndrome (ALPS patients, prompting us to examine Fas-independent, intrinsic signals. Results Upon TCR restimulation, we specifically noted a marked increase in the expression of BIM, a pro-apoptotic Bcl-2 family protein known to mediate lymphocyte apoptosis induced by cytokine withdrawal. In fact, T cells from an ALPS type IV patient in which BIM expression is suppressed were more resistant to restimulation-induced death. Strikingly, knockdown of BIM expression rescued normal T cells from TCR-induced death to as great an extent as Fas disruption. Conclusion Our data implicates BIM as a critical mediator of apoptosis induced by restimulation as well as growth cytokine withdrawal. These findings suggest an important role for BIM in eliminating activated T cells even when IL-2 is abundant, working in conjunction with Fas to eliminate chronically stimulated T cells and maintain immune homeostasis. Reviewers This article was reviewed by Dr. Wendy Davidson (nominated by Dr. David Scott, Dr. Mark Williams (nominated by Dr. Neil Greenspan, and Dr. Laurence C. Eisenlohr.

  18. The critical role of catalase in prooxidant and antioxidant function of p53

    Science.gov (United States)

    Kang, M Y; Kim, H-B; Piao, C; Lee, K H; Hyun, J W; Chang, I-Y; You, H J

    2013-01-01

    The tumor suppressor p53 is an important regulator of intracellular reactive oxygen species (ROS) levels, although downstream mediators of p53 remain to be elucidated. Here, we show that p53 and its downstream targets, p53-inducible ribonucleotide reductase (p53R2) and p53-inducible gene 3 (PIG3), physically and functionally interact with catalase for efficient regulation of intracellular ROS, depending on stress intensity. Under physiological conditions, the antioxidant functions of p53 are mediated by p53R2, which maintains increased catalase activity and thereby protects against endogenous ROS. After genotoxic stress, high levels of p53 and PIG3 cooperate to inhibit catalase activity, leading to a shift in the oxidant/antioxidant balance toward an oxidative status, which could augment apoptotic cell death. These results highlight the essential role of catalase in p53-mediated ROS regulation and suggest that the p53/p53R2–catalase and p53/PIG3–catalase pathways are critically involved in intracellular ROS regulation under physiological conditions and during the response to DNA damage, respectively. PMID:22918438

  19. Microtubule-Mediated Inositol Lipid Signaling Plays Critical Roles in Regulation of Blebbing.

    Directory of Open Access Journals (Sweden)

    Tatsuroh Sugiyama

    Full Text Available Cells migrate by extending pseudopods such as lamellipodia and blebs. Although the signals leading to lamellipodia extension have been extensively investigated, those for bleb extension remain unclear. Here, we investigated signals for blebbing in Dictyostelium cells using a newly developed assay to induce blebbing. When cells were cut into two pieces with a microneedle, the anucleate fragments vigorously extended blebs. This assay enabled us to induce blebbing reproducibly, and analyses of knockout mutants and specific inhibitors identified candidate molecules that regulate blebbing. Blebs were also induced in anucleate fragments of leukocytes, indicating that this assay is generally applicable to animal cells. After cutting, microtubules in the anucleate fragments promptly depolymerized, followed by the extension of blebs. Furthermore, when intact cells were treated with a microtubule inhibitor, they frequently extended blebs. The depolymerization of microtubules induced the delocalization of inositol lipid phosphatidylinositol 3,4,5-trisphosphate from the cell membrane. PI3 kinase-null cells frequently extended blebs, whereas PTEN-null cells extended fewer blebs. From these observations, we propose a model in which microtubules play a critical role in bleb regulation via inositol lipid metabolism.

  20. The Critical Role of Substrate in Stabilizing Phosphorene Nanoflake: A Theoretical Exploration.

    Science.gov (United States)

    Gao, Junfeng; Zhang, Gang; Zhang, Yong-Wei

    2016-04-13

    Phosphorene, a new two-dimensional (2D) semiconductor, has received much interest due to its robust direct band gap and high charge mobility. Currently, however, phosphorene can only be produced by mechanical or liquid exfoliation, and it is still a significant challenge to directly epitaxially grow phosphorene, which greatly hinders its mass production and, thus, applications. In epitaxial growth, the stability of nanoscale cluster or flake on a substrate is crucial. Here, we perform ab initio energy optimizations and molecular dynamics simulations to explore the critical role of substrate on the stability of a representative phosphorene flake. Our calculations show that the stability of the phosphorene nanoflake is strongly dependent on the interaction strength between the nanoflake and substrate. Specifically, the strong interaction (0.75 eV/P atom) with Cu(111) substrate breaks up the phosphorene nanoflake, while the weak interaction (0.063 eV/P atom) with h-BN substrate fails to stabilize its 2D structure. Remarkably, we find that a substrate with a moderate interaction (about 0.35 eV/P atom) is able to stabilize the 2D characteristics of the nanoflake on a realistic time scale. Our findings here provide useful guidelines for searching suitable substrates for the directly epitaxial growth of phosphorene.

  1. Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease

    Science.gov (United States)

    Cruz, Nelly M.; Song, Xuewen; Czerniecki, Stefan M.; Gulieva, Ramila E.; Churchill, Angela J.; Kim, Yong Kyun; Winston, Kosuke; Tran, Linh M.; Diaz, Marco A.; Fu, Hongxia; Finn, Laura S.; Pei, York; Himmelfarb, Jonathan; Freedman, Benjamin S.

    2017-11-01

    Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular epithelia form fluid-filled cysts. A major barrier to understanding PKD is the absence of human cellular models that accurately and efficiently recapitulate cystogenesis. Previously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidney organoids. Here we show that systematic substitution of physical components can dramatically increase or decrease cyst formation, unveiling a critical role for microenvironment in PKD. Removal of adherent cues increases cystogenesis 10-fold, producing cysts phenotypically resembling PKD that expand massively to 1-centimetre diameters. Removal of stroma enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression and collagen compaction. Cyclic adenosine monophosphate (cAMP), when added, induces cysts in both PKD organoids and controls. These biomaterials establish a highly efficient model of PKD cystogenesis that directly implicates the microenvironment at the earliest stages of the disease.

  2. Critical role of climate change in plant selection and millet domestication in North China.

    Science.gov (United States)

    Yang, Xiaoyan; Wu, Wenxiang; Perry, Linda; Ma, Zhikun; Bar-Yosef, Ofer; Cohen, David J; Zheng, Hongbo; Ge, Quansheng

    2018-05-18

    While North China is one of the earliest independent centers for cereal domestication in the world, the earliest stages of the long process of agricultural origins remain unclear. While only millets were eventually domesticated in early sedentary societies there, recent archaeobotanical evidence reported here indicates that grasses from the Paniceae (including millets) and Triticeae tribes were exploited together by foraging groups from the Last Glacial Maximum to the mid-Holocene. Here we explore how and why millets were selected for domestication while Triticeae were abandoned. We document the different exploitation and cultivation trajectories of the two tribes employing ancient starch data derived from nine archaeological sites dating from 25,000 to 5500 cal BP (LGM through mid-Holocene) in North China. With this diachronic overview, we can place the trajectories into the context of paleoclimatic reconstructions for this period. Entering the Holocene, climatic changes increased the yield stability, abundance, and availability of the wild progenitors of millets, with growing conditions increasingly favoring millets while becoming more unfavorable for grasses of the Triticeae tribe. We thus hypothesize that climate change played a critical role in the selection of millet species for domestication in North China, with early domestication evidenced by 8700 cal BP.

  3. Teaching materials: a critical position about the role they play in the language classroom

    Directory of Open Access Journals (Sweden)

    Araya Araya, Karla

    2007-12-01

    conceptual study about theoretical assumptions related to the importance and the role teaching materials have in the language teaching-learning process has been carried out. Also, there is a general analysis regarding the relationship among teaching materials, motivation and ideology. Finally, it can be concluded that materials are reproductions and constructors of certain discursive and ideological realities that usually favor the interests of the dominant classes. That is why a critical position about the role teaching materials have is necessary to prevent the reproduction of prejudices and common sense assumptions about language and society.

  4. Numerical investigations of cooling holes system role in the protection of the walls of a gas turbine combustion chamber

    Energy Technology Data Exchange (ETDEWEB)

    Ben Sik Ali, Ahlem; Kriaa, Wassim; Mhiri, Hatem [Ecole Nationale D' Ingenieurs de Monastir, Unite de Thermique et Thermodynamique des Procedes industriels, Monastir (Tunisia); Bournot, Philippe [IUSTI, UMR CNRS 6595, Marseille (France)

    2012-05-15

    Numerical simulations in a gas turbine Swirl stabilized combustor were conducted to investigate the effectiveness of a cooling system in the protection of combustor walls. The studied combustion chamber has a high degree of geometrical complexity related to the injection system as well as the cooling system based on a big distribution of small holes (about 3,390 holes) bored on the flame tube walls. Two cases were considered respectively the flame tube without and with its cooling system. The calculations were carried out using the industrial CFD code FLUENT 6.2. The various simulations made it possible to highlight the role of cooling holes in the protection of the flame tube walls against the high temperatures of the combustion products. In fact, the comparison between the results of the two studied cases demonstrated that the walls temperature can be reduced by about 800 C by the mean of cooling holes technique. (orig.)

  5. Role of Water Vapor Content in the Effects of Aerosol on the Electrification of Thunderstorms: A Numerical Study

    Directory of Open Access Journals (Sweden)

    Pengguo Zhao

    2016-10-01

    Full Text Available We explored the role of the water vapor content below the freezing level in the response of idealized supercell storm electrical processes to increased concentrations of cloud condensation nuclei (CCN. Using the Weather Research and Forecasting model coupled with parameterizations electrification and discharging, we performed 30 simulations by varying both the CCN concentration and water vapor content below the freezing level. The sensitivity simulations showed a distinct response to increased concentrations of CCN, depending on the water vapor content below the freezing level. Enhancing CCN concentrations increased electrification processes of thunderstorms and produced a new negative charge region above the main positive charge center when there were ample amounts of water vapor below the freezing level. Conversely, there were weak effects on electrification and the charge structure in numerical experiments initialized with lower water vapor content below the freezing level.

  6. Toward an improved understanding of the role of transpiration in critical zone dynamics

    Science.gov (United States)

    Mitra, B.; Papuga, S. A.

    2012-12-01

    , during the snowmelt period, Ts across multiple depths was the primary control on the sap flux rate (R2 ≈ 0.7). During the dry and monsoon periods only net radiation (Rn) was found to be a driver of the flux rate (R2 ≈ 0.4). For JRB spruce, a combination of Ts across multiple depths as well as air temperature (R2 ≈ 0.5) were the dominant drivers of sap flux rate during the snowmelt period. During the monsoon period, Rn (R2 ≈ 0.4) was the dominant driver. For SCM maple, during the dry period, θ across multiple depths was the primary driver of the sap flux rate (R2 ≈ 0.8); the strength of the correlation with the control of θ on sap flux rate drastically dropping (R2 ≈ 0.2) during the monsoon period. For SCM white fir, θ across multiple depths was a weak driver of sap flux rate during the dry (R2 ≈ 0.1) and monsoon periods (R2 ≈ 0.2). This study highlights the importance of species-specific information for understanding the role of transpiration in critical zone processes. Specifically, unique environmental drivers that vary throughout the year for different vegetation types complicate the assessment of both catchment-scale water and carbon balances and for understanding of the processes that govern the complex dynamics across the CZ.

  7. Numerical simulation of CO2 leakage from a geologic disposal reservoir, including transitions from super- to sub-critical conditions, and boiling of liquid of CO2

    International Nuclear Information System (INIS)

    Pruess, Karsten

    2003-01-01

    The critical point of CO 2 is at temperature and pressure conditions of T crit = 31.04 C, P crit = 73.82 bar. At lower (subcritical) temperatures and/or pressures, CO 2 can exist in two different phase states, a liquid and a gaseous state, as well as in two-phase mixtures of these states. Disposal of CO 2 into brine formations would be made at supercritical pressures. However, CO 2 escaping from the storage reservoir may migrate upwards towards regions with lower temperatures and pressures, where CO 2 would be in subcritical conditions. An assessment of the fate of leaking CO 2 requires a capability to model not only supercritical but also subcritical CO 2 , as well as phase changes between liquid and gaseous CO 2 in sub-critical conditions. We have developed a methodology for numerically simulating the behavior of water-CO 2 mixtures in permeable media under conditions that may include liquid, gaseous, and supercritical CO 2 . This has been applied to simulations of leakage from a deep storage reservoir in which a rising CO 2 plume undergoes transitions from supercritical to subcritical conditions. We find strong cooling effects when liquid CO 2 rises to elevations where it begins to boil and evolve a gaseous CO 2 phase. A three-phase zone forms (aqueous - liquid - gas), which over time becomes several hundred meters thick as decreasing temperatures permit liquid CO 2 to advance to shallower elevations. Fluid mobilities are reduced in the three-phase region from phase interference effects. This impedes CO 2 upflow, causes the plume to spread out laterally, and gives rise to dispersed CO 2 discharge at the land surface. Our simulation suggests that temperatures along a CO 2 leakage path may decline to levels low enough so that solid water ice and CO 2 hydrate phases may be formed

  8. The Dual Role of Vegetation as a Constraint on Mass and Energy Flux into the Critical Zone and as an Emergent Property of Geophysical Critical Zone Structure

    Science.gov (United States)

    Brooks, P. D.; Swetnam, T. L.; Barnard, H. R.; Singha, K.; Harpold, A.; Litvak, M. E.

    2017-12-01

    Spatial patterns in vegetation long have been used to scale both landsurface-atmosphere exchanges of water and carbon as well as to infer subsurface structure. These pursuits typical proceed in isolation and rarely do inferences gained from one community propagate to related efforts in another. Perhaps more importantly, vegetation often is treated as an emergent property of landscape-climate interactions rather than an active modifier of both critical zone structure and energy fluxes. We posit that vegetation structure and activity are under utilized as a tool towards understanding landscape evolution and present examples that begin to disentangle the role of vegetation as both an emergent property and an active control on critical zone structure and function. As climate change, population growth, and land use changes threaten water resources worldwide, the need for the new insights vegetation can provide becomes not just a basic science priority, but a pressing applied science question with clear societal importance. This presentation will provide an overview of recent efforts to address the dual role of vegetation in both modifying and reflecting critical zone structure in the western North American forests. For example, interactions between topography and stand scale vegetation structure influence both solar radiation and turbulence altering landscape scale partitioning of evaporation vs transpiration with major impacts of surface water supply. Similarly, interactions between topographic shading, lateral redistribution of plant available water, and subsurface storage create a mosaic of drought resistance and resilience across complex terrain. These complex interactions between geophysical and vegetation components of critical zone structure result in predictable patterns in catchment scale hydrologic partitioning within individual watersheds while simultaneously suggesting testable hypotheses for why catchments under similar climate regimes respond so

  9. A critical examination of the role of appreciative inquiry within an interprofessional education initiative.

    Science.gov (United States)

    Dematteo, Dale; Reeves, Scott

    2011-05-01

    Appreciative inquiry (AI) is a relatively new approach to initiating or managing organizational change that is associated with the 'positiveness' movement in psychology and its offshoot positive organizational scholarship. Rather than dwelling upon problems related to change, AI encourages individuals to adopt a positive, constructive approach to managing change. In recent years, AI has been used to initiate change across a broad range of public and private sector organizations. In this article, we report findings from a subset of 50 interviews gathered in a wider study of interprofessional education (IPE) in which AI was employed as a change agent for implementing IPE in a number of health care institutions in a North American setting. A multiple case study approach. (Yin, 2002) was employed in the wider study and semi-structured interviews were undertaken with participants both before their IPE programs and directly afterwards to obtain a detailed understanding of their expectations and experiences of IPE. Interviews were analyzed in an inductive thematic manner in order to produce key emergent themes from each of the IPE programs. A process of re-analysis provided a set of themes which offered an understanding of the role of AI within this IPE initiative. Our findings identify a strong resonance and fit for AI both among the health and social care professionals who participated in this initiative. Numerous individuals commented on the enthusiasm and energy AI engendered, while praising its ability to enhance their working lives and interprofessional relationships. Yet a number of difficulties were also reported. These focused on problems with the translation of the AI process into achievable structural level (e.g. professional, cultural) changes. Based on these findings, the article goes on to argue that the use of AI can overlook a number of structural factors, which will ultimately limit its ability to actually secure meaningful and lasting change within

  10. Can We Protect the Gut in Critical Illness: The Role of Growth Factors and Other Novel Approaches

    OpenAIRE

    Dominguez, Jessica A.; Coopersmith, Craig M.

    2010-01-01

    The intestine plays a central role in the pathophysiology of critical illness and is frequently called the “motor” of the systemic inflammatory response. Perturbations to the intestinal barrier can lead to distant organ damage and multiple organ failure. Therefore, identifying ways to preserve intestinal integrity may be of paramount importance. Growth factors and other peptides have emerged as potential tools for modulation of intestinal inflammation and repair due to their roles in cellular...

  11. ROLE OF MAGNETIC FIELD STRENGTH AND NUMERICAL RESOLUTION IN SIMULATIONS OF THE HEAT-FLUX-DRIVEN BUOYANCY INSTABILITY

    International Nuclear Information System (INIS)

    Avara, Mark J.; Reynolds, Christopher S.; Bogdanović, Tamara

    2013-01-01

    The role played by magnetic fields in the intracluster medium (ICM) of galaxy clusters is complex. The weakly collisional nature of the ICM leads to thermal conduction that is channeled along field lines. This anisotropic heat conduction profoundly changes the instabilities of the ICM atmosphere, with convective stabilities being driven by temperature gradients of either sign. Here, we employ the Athena magnetohydrodynamic code to investigate the local non-linear behavior of the heat-flux-driven buoyancy instability (HBI) relevant in the cores of cooling-core clusters where the temperature increases with radius. We study a grid of two-dimensional simulations that span a large range of initial magnetic field strengths and numerical resolutions. For very weak initial fields, we recover the previously known result that the HBI wraps the field in the horizontal direction, thereby shutting off the heat flux. However, we find that simulations that begin with intermediate initial field strengths have a qualitatively different behavior, forming HBI-stable filaments that resist field-line wrapping and enable sustained vertical conductive heat flux at a level of 10%-25% of the Spitzer value. While astrophysical conclusions regarding the role of conduction in cooling cores require detailed global models, our local study proves that systems dominated by the HBI do not necessarily quench the conductive heat flux

  12. Role-meanings as a critical factor in understanding doctor managers' identity work and different role identities.

    Science.gov (United States)

    Cascón-Pereira, Rosalía; Chillas, Shiona; Hallier, Jerry

    2016-12-01

    This study examines "identity work" among hybrid doctor-managers (DMs) in the Spanish National Health System to make sense of their managerial roles. In particular, the meanings underlying DMs experience of their hybrid role are investigated using a Grounded Theory methodology, exposing distinctions in role-meanings. Our findings provide evidence that using different social sources of comparison (senior managers or clinicians) to construct the meaning of managerial roles leads to different role-meanings and role identities, which are the source of the two established types of DM in the literature, the reluctant and the enthusiast. The contribution is twofold: our findings lead us to theorize DMs' identity work processes by adding an overlooked role-meaning dimension to identity work; and raise practical reflections for those who wish to develop enthusiast doctor managers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Distress in couples coping with cancer : A meta-analysis and critical review of role and gender effects

    NARCIS (Netherlands)

    Hagedoorn, Mariet; Sanderman, Robbert; Bolks, Hilde N.; Tuinstra, Jolanda; Coyne, James C.

    Research concerning distress in couples coping with cancer was integrated using meta-analysis and narrative critical appraisal. Individual levels of distress were determined more by gender than by the role of being the person with cancer versus that person's partner. That is, women reported

  14. Editorial Commentary: Hip Arthroscopy Plays a Role in Painful Hip Resurfacing Arthroplasty but a Prearthroscopy Diagnosis Is Critical to Outcome.

    Science.gov (United States)

    Rossi, Michael J

    2016-03-01

    Whereas hip arthroscopy plays a role in the investigation and treatment of the painful hip resurfacing arthroplasty, a diagnosis before arthroscopy is critical to improved outcome. The rate of conversion to total hip arthroplasty jumps from 7% to 37% when a pre-arthroscopy diagnosis is not known. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  15. Preventing and managing exacerbations in COPD – critical appraisal of the role of tiotropium

    Directory of Open Access Journals (Sweden)

    Donald P Tashkin

    2010-02-01

    Full Text Available Donald P TashkinDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA,Los Angeles, CA, USAAbstract: The course of COPD is punctuated by acute exacerbations that are associated with an increase in the morbidity and mortality related to this chronic disease and may contribute to its rate of progression. Therefore, preventing and treating exacerbations are major goals of COPD management. The role of tiotropium in the prevention of exacerbations has been investigated in several placebo-controlled randomized clinical trials varying in duration from 3 months to 4 years in patients with moderate to very severe COPD. In all of these trials, tiotropium has uniformly reduced the proportion of patients experiencing at least one exacerbation and delayed the time to the first exacerbation compared with placebo. In the longer trials (≥6 months’ duration tiotropium has also reduced the exposure-adjusted incidence rate of exacerbations. In trials of at least 1 year in duration, tiotropium either significantly reduced the risk of hospitalization for an exacerbation and/or the proportion of patients with an exacerbation-related hospitalization. In a meta-analysis that included 15 trials of tiotropium vs either placebo (n = 13 and/or a longacting beta-agonist (LABA; n = 4, tiotropium significantly reduced the odds of experiencing an exacerbation compared to placebo as well as a LABA. The potential additive benefits of tiotropium to those of a LABA and/or inhaled corticosteroid in reducing exacerbations require further investigation. The mechanism whereby tiotropium reduces exacerbations is not due to an anti-inflammatory effect but more likely relates to its property of causing a sustained increase in airway patency and reduction in hyperinflation, thereby counteracting the tendency for respiratory insults to worsen airflow obstruction and hyperinflation. For the management of acute exacerbations, an

  16. Recognition of TLR2 N-Glycans: Critical Role in ArtinM Immunomodulatory Activity

    Science.gov (United States)

    da Silva, Thiago Aparecido; Ruas, Luciana Pereira; Nohara, Lilian L.; de Almeida, Igor Correia; Roque-Barreira, Maria Cristina

    2014-01-01

    TLR2 plays a critical role in the protection against Paracoccidioides brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and dendritic cells, which accounts for the T helper1 immunity that results from ArtinM administration. We examined the direct interaction of ArtinM with TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1 or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF-κB activation and interleukin (IL)-8 production in cells transfected with TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that had been captured by specific antibodies from a macrophages lysate. Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre-incubated with mannotriose. The biological relevance of the direct interaction of ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than macrophages from wild-type mice. Pre-treatment of murine macrophages with pharmacological inhibitors of signaling molecules demonstrated the involvement of p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2 heterodimers in a carbohydrate recognition-dependent manner and functions as a TLR2 agonist with immunomodulatory properties. PMID:24892697

  17. Recognition of TLR2 N-glycans: critical role in ArtinM immunomodulatory activity.

    Directory of Open Access Journals (Sweden)

    Vania Sammartino Mariano

    Full Text Available TLR2 plays a critical role in the protection against Paracoccidioides brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and dendritic cells, which accounts for the T helper1 immunity that results from ArtinM administration. We examined the direct interaction of ArtinM with TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1 or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF-κB activation and interleukin (IL-8 production in cells transfected with TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that had been captured by specific antibodies from a macrophages lysate. Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre-incubated with mannotriose. The biological relevance of the direct interaction of ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than macrophages from wild-type mice. Pre-treatment of murine macrophages with pharmacological inhibitors of signaling molecules demonstrated the involvement of p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2 heterodimers in a carbohydrate recognition-dependent manner and functions as a TLR2 agonist with immunomodulatory properties.

  18. Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance

    Science.gov (United States)

    Jin, Jianliang; Lv, Xianhui; Chen, Lulu; Zhang, Wei; Li, Jinbo; Wang, Qian; Wang, Rong; Lu, Xiang; Miao, Dengshun

    2014-01-01

    To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quinone (PQQ, 4 mg kg−1 diet) in their diet for 2 weeks, and their renal phenotypes were compared with vehicle-treated Bmi1-/- and wild-type mice. Bmi-1 was knocked down in human renal proximal tubular epithelial (HK2) cells which were treated with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control cells. Five-week-old vehicle-treated Bmi-1-/- mice displayed renal interstitial fibrosis, tubular atrophy, and severe renal function impairment with decreased renal cell proliferation, increased renal cell apoptosis and senescence, and inflammatory cell infiltration. Impaired mitochondrial structure, decreased mitochondrial numbers, and increased oxidative stress occurred in Bmi-1-/- mice; subsequently, this caused DNA damage, the activation of TGF-β1/Smad signaling, and the imbalance between extracellular matrix synthesis and degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant treatment. These findings indicate that Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance and will be a novel therapeutic target for preventing renal tubulointerstitial injury. PMID:24915841

  19. Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression

    International Nuclear Information System (INIS)

    Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X.; Walterscheid, Jeffrey P.; Ullrich, Stephen E.

    2004-01-01

    Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependant manner. The release of biological response modifiers, particularly prostaglandin E 2 (PGE 2 ), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE 2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE 2 secretion. Jet fuel-induced PGE 2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin

  20. The role of monoamines in the actions of established and "novel" antidepressant agents: a critical review.

    Science.gov (United States)

    Millan, Mark J

    2004-10-01

    Monoaminergic pathways are highly responsive to aversive stimuli and play a crucial role in the control of affect, cognition, endocrine secretion, chronobiotic rhythms, appetite, and motor function, all of which are profoundly disrupted in depressive states. Accordingly, a perturbation of monoaminergic transmission is implicated in the aetiology of depressive disorders, and all clinically available antidepressants increase corticolimbic availability of monoamines. However, their limited efficacy, delayed onset of action, and undesirable side effects underlie ongoing efforts to identify improved therapeutic agents. Sequencing the human genome has raised the hope not only of better symptomatic control of depression, but even of the prevention or cure of depressive states. In the pursuit of these goals, there is currently a tendency to focus on selective ligands of "novel" nonmonoaminergic targets. However, certain classes of novel agent (such as neurokinin(1) receptor antagonists) indirectly modulate the activity of monoaminergic networks. Others may act "downstream" of them, converging onto common cellular substrates controlling gene expression, synaptic plasticity, and neurogenesis. Further, by analogy to the broad-based actions of currently employed drugs, multitarget agents may be better adapted than selective agents to the management of depression-a complex disorder with hereditary, developmental, and environmental origins. It is, thus, important to continue the creative exploration of clinically validated and innovative monoaminergic strategies within a multitarget framework. In this light, drugs combining monoaminergic and nonmonoaminergic mechanisms of action may be of particular interest. The present article provides a critical overview of monoaminergic strategies for the treatment of depressive states, both established and under development, and discusses interactions of novel "nonmonoaminergic" antidepressants with monoaminergic mechanisms.

  1. A critical role of glutamate transporter type 3 in the learning and memory of mice.

    Science.gov (United States)

    Wang, Zhi; Park, Sang-Hon; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi

    2014-10-01

    Hippocampus-dependent learning and memory are associated with trafficking of excitatory amino acid transporter type 3 (EAAT3) to the plasma membrane. To assess whether this trafficking is an intrinsic component of the biochemical responses underlying learning and memory, 7- to 9-week old male EAAT3 knockout mice and CD-1 wild-type mice were subjected to fear conditioning. Their hippocampal CA1 regions, amygdalae and entorhinal cortices were harvested before, or 30 min or 3 h after the fear conditioning stimulation. We found that EAAT3 knockout mice had worse contextual and tone-related learning and memory than did the wild-type mice. The expression of EAAT3, glutamate receptor (GluR)1 and GluR2 in the plasma membrane and of phospho-GluR1 (at Ser 831) and phospho-CaMKII in the hippocampus of the wild-type mice was increased at 30 min after the fear conditioning stimulation. Similar biochemical changes occurred in the amygdala. Fear conditioning also increased the expression of c-Fos and activity-regulated cytoskeleton-associated protein (Arc) in the CA1 regions and of Arc in the entorhinal cortices of the wild-type mice. These biochemical responses were attenuated in the EAAT3 knockout mice. These results suggest that EAAT3 plays a critical role in learning and memory. Our results also provide initial evidence that EAAT3 may have receptor-like functions to participate in the biochemical reactions underlying learning and memory. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Critical roles of orthopaedic surgeon leadership in healthcare systems to improve orthopaedic surgical patient safety.

    Science.gov (United States)

    Kuo, Calvin C; Robb, William J

    2013-06-01

    The prevention of medical and surgical harm remains an important public health problem despite increased awareness and implementation of safety programs. Successful introduction and maintenance of surgical safety programs require both surgeon leadership and collaborative surgeon-hospital alignment. Documentation of success of such surgical safety programs in orthopaedic practice is limited. We describe the scope of orthopaedic surgical patient safety issues, define critical elements of orthopaedic surgical safety, and outline leadership roles for orthopaedic surgeons needed to establish and sustain a culture of safety in contemporary healthcare systems. We identified the most common causes of preventable surgical harm based on adverse and sentinel surgical events reported to The Joint Commission. A comprehensive literature review through a MEDLINE(®) database search (January 1982 through April 2012) to identify pertinent orthopaedic surgical safety articles found 14 articles. Where gaps in orthopaedic literature were identified, the review was supplemented by 22 nonorthopaedic surgical references. Our final review included 36 articles. Six important surgical safety program elements needed to eliminate preventable surgical harm were identified: (1) effective surgical team communication, (2) proper informed consent, (3) implementation and regular use of surgical checklists, (4) proper surgical site/procedure identification, (5) reduction of surgical team distractions, and (6) routine surgical data collection and analysis to improve the safety and quality of surgical patient care. Successful surgical safety programs require a culture of safety supported by all six key surgical safety program elements, active surgeon champions, and collaborative hospital and/or administrative support designed to enhance surgical safety and improve surgical patient outcomes. Further research measuring improvements from such surgical safety systems in orthopaedic care is needed.

  3. Numerical prediction of critical heat flux in nuclear fuel rod bundles with advanced three-fluid multidimensional porous media based model

    International Nuclear Information System (INIS)

    Zoran Stosic; Vladimir Stevanovic

    2005-01-01

    Full text of publication follows: The modern design of nuclear fuel rod bundles for Boiling Water Reactors (BWRs) is characterised with increased number of rods in the bundle, introduced part-length fuel rods and a water channel positioned along the bundle asymmetrically in regard to the centre of the bundle cross section. Such design causes significant spatial differences of volumetric heat flux, steam void fraction distribution, mass flux rate and other thermal-hydraulic parameters important for efficient cooling of nuclear fuel rods during normal steady-state and transient conditions. The prediction of the Critical Heat Flux (CHF) under these complex thermal-hydraulic conditions is of the prime importance for the safe and economic BWR operation. An efficient numerical method for the CHF prediction is developed based on the porous medium concept and multi-fluid two-phase flow models. Fuel rod bundle is observed as a porous medium with a two-phase flow through it. Coolant flow from the bundle entrance to the exit is characterised with the subsequent change of one-phase and several two-phase flow patterns. One fluid (one-phase) model is used for the prediction of liquid heating up in the bundle entrance region. Two-fluid modelling approach is applied to the bubbly and churn-turbulent vapour and liquid flows. Three-fluid modelling approach is applied to the annular flow pattern: liquid film on the rods wall, steam flow and droplets entrained in the steam stream. Every fluid stream in applied multi-fluid models is described with the mass, momentum and energy balance equations. Closure laws for the prediction of interfacial transfer processes are stated with the special emphasis on the prediction of the steam-water interface drag force, through the interface drag coefficient, and droplets entrainment and deposition rates for three-fluid annular flow model. The model implies non-equilibrium thermal and flow conditions. A new mechanistic approach for the CHF prediction

  4. [Role of creative discussion in the learning of critical reading of scientific articles].

    Science.gov (United States)

    Cobos-Aguilar, Héctor; Viniegra-Velázquez, Leonardo; Pérez-Cortés, Patricia

    2011-01-01

    To compare two active educational strategies on critical reading (two and three stages) for research learning in medical students. Four groups were conformed in a quasi-experimental design. The medical student group, related to three stages (critical reading guide resolution, creative discussion, group discussion) g1, n = 9 with school marks > 90 and g2, n = 19 with a learning in our students.

  5. The Future Role of GIS Education in Creating Critical Spatial Thinkers

    Science.gov (United States)

    Bearman, Nick; Jones, Nick; André, Isabel; Cachinho, Herculano Alberto; DeMers, Michael

    2016-01-01

    Teaching of critical spatial thinking in higher education empowers graduates to effectively engage with spatial data. Geographic information systems (GIS) and science are taught to undergraduates across many disciplines; we evaluate how this contributes to critical spatial thinking. The discipline of GIS covers the whole process of spatial…

  6. Racial Inequality in Critical Thinking Skills: The Role of Academic and Diversity Experiences

    Science.gov (United States)

    Roksa, Josipa; Trolian, Teniell L.; Pascarella, Ernest T.; Kilgo, Cindy A.; Blaich, Charles; Wise, Kathleen S.

    2017-01-01

    While racial inequalities in college entry and completion are well documented, much less is known about racial disparities in the development of general collegiate skills, such as critical thinking. Using data from the Wabash National Study of Liberal Arts Education, we find substantial inequality in the development of critical thinking skills…

  7. Specifying a Curriculum for Biopolitical Critical Literacy in Science Teacher Education: Exploring Roles for Science Fiction

    Science.gov (United States)

    Gough, Noel

    2017-01-01

    In this essay I suggest some ways in which science teacher educators in Western neoliberal economies might facilitate learners' development of a critical literacy concerning the social and cultural changes signified by the concept of "biopolitics." I consider how such a biopolitically inflected critical literacy might find expression in…

  8. A Culture of Thinking Like a Teacher: The Role of Critical Reflection in Teacher Preparation

    Science.gov (United States)

    Lowenstein, Karen L.; Brill, Andra

    2010-01-01

    As teacher educators for an alternative urban teacher preparation program, we believe that because we cannot teach novice teachers everything they need to know in one year, our principal responsibility is to teach our novices to think like teachers. Central to this process is supporting novices to engage in critical reflection. Critical reflection…

  9. Investigating Predictive Role of Critical Thinking on Metacognition with Structural Equation Modeling

    Science.gov (United States)

    Arslan, Serhat

    2015-01-01

    The purpose of this study is to examine the relationships between critical thinking and metacognition. The sample of study consists of 390 university students who were enrolled in different programs at Sakarya University, in Turkey. In this study, the Critical Thinking Disposition Scale and Metacognitive Thinking Scale were used. The relationships…

  10. Evidence and its uses in health care and research: the role of critical thinking.

    Science.gov (United States)

    Jenicek, Milos; Croskerry, Pat; Hitchcock, David L

    2011-01-01

    Obtaining and critically appraising evidence is clearly not enough to make better decisions in clinical care. The evidence should be linked to the clinician's expertise, the patient's individual circumstances (including values and preferences), and clinical context and settings. We propose critical thinking and decision-making as the tools for making that link. Critical thinking is also called for in medical research and medical writing, especially where pre-canned methodologies are not enough. It is also involved in our exchanges of ideas at floor rounds, grand rounds and case discussions; our communications with patients and lay stakeholders in health care; and our writing of research papers, grant applications and grant reviews. Critical thinking is a learned process which benefits from teaching and guided practice like any discipline in health sciences. Training in critical thinking should be a part or a pre-requisite of the medical curriculum.

  11. Evidence and its uses in health care and research: The role of critical thinking

    Science.gov (United States)

    Jenicek, Milos; Croskerry, Pat; Hitchcock, David L.

    2011-01-01

    Summary Obtaining and critically appraising evidence is clearly not enough to make better decisions in clinical care. The evidence should be linked to the clinician’s expertise, the patient’s individual circumstances (including values and preferences), and clinical context and settings. We propose critical thinking and decision-making as the tools for making that link. Critical thinking is also called for in medical research and medical writing, especially where pre-canned methodologies are not enough. It is also involved in our exchanges of ideas at floor rounds, grand rounds and case discussions; our communications with patients and lay stakeholders in health care; and our writing of research papers, grant applications and grant reviews. Critical thinking is a learned process which benefits from teaching and guided practice like any discipline in health sciences. Training in critical thinking should be a part or a pre-requisite of the medical curriculum. PMID:21169920

  12. Nurses' role transition from the clinical ward environment to the critical care environment.

    Science.gov (United States)

    Gohery, Patricia; Meaney, Teresa

    2013-12-01

    To explore the experiences of nurses moving from the ward environment to the critical care environment. Critical care areas are employing nurses with no critical care experience due to staff shortage. There is a paucity of literature focusing on the experiences of nurses moving from the ward environment to the critical care environment. A Heideggerian phenomenology research approach was used in this study. In-depth semi structured interviews, supported with an interview guide, were conducted with nine critical care nurses. Data analysis was guided by Van Manen (1990) approach to phenomenological analysis. Four main themes emerged: The highs and lows, you need support, theory-practice gap, struggling with fear. The participants felt ill prepared and inexperienced to work within the stressful and technical environment of critical care due to insufficient education and support. The study findings indicated that a variety of feelings and emotions are experienced by ward nurses who move into the stressful and technical environment of critical care due to insufficient skills and knowledge. More education and support is required to improve this transition process. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. The impact of social roles on trait judgments: a critical reexamination.

    Science.gov (United States)

    Bosak, Janine; Sczesny, Sabine; Eagly, Alice H

    2012-04-01

    Consistent with social role theory's assumption that the role behavior of men and women shapes gender stereotypes, earlier experiments have found that men's and women's occupancy of the same role eliminated gender-stereotypical judgments of greater agency and lower communion in men than women. The shifting standards model raises the question of whether a shift to within-sex standards in judgments of men and women in roles could have masked underlying gender stereotypes. To examine this possibility, two experiments obtained judgments of men and women using measures that do or do not restrain shifts to within-sex standards. This measure variation did not affect the social role pattern of smaller perceived sex differences in the presence of role information. These findings thus support the social role theory claim that designations of identical roles for subgroups of men and women eliminate or reduce perceived sex differences.

  14. Modeling the role of microplastics in Bioaccumulation of organic chemicals to marine aquatic organisms. Critical Review

    NARCIS (Netherlands)

    Koelmans, A.A.

    2015-01-01

    It has been shown that ingestion of microplastics may increase bioaccumulation of organic chemicals by aquatic organisms. This paper critically reviews the literature on the effects of plastic ingestion on the bioaccumulation of organic chemicals, emphasizing quantitative approaches and mechanistic

  15. Detecting critical illness outside the ICU: the role of track and trigger systems.

    Science.gov (United States)

    Jansen, Jan O; Cuthbertson, Brian H

    2010-06-01

    Critical illness is often preceded by physiological deterioration. Track and trigger systems are intended to facilitate the timely recognition of patients with potential or established critical illness outside critical care areas. The aim of this article is to review the evidence for the use of such systems. Existing track and trigger systems have low sensitivity, low positive predictive values, and high specificity. They often fail to identify patients who need additional care and have not been shown to improve outcomes. The development of such systems must be based on robust methodological and statistical principles. At present, few track and trigger systems meet these standards. Although track and trigger systems, combined with appropriate response algorithms, have the potential to improve the recognition and management of critical illness, further work is required to validate their utility.

  16. How does the color influence figure and shape formation, grouping, numerousness and reading? The role of chromatic wholeness and fragmentation.

    Science.gov (United States)

    Pinna, Baingio; Uccula, Arcangelo; Tanca, Maria

    2010-09-01

    In this work it is suggested that color induces phenomenal wholeness, part-whole organization and fragmentation. The phenomenal wholeness subsumes the set of its main attributes: homogeneity, continuity, univocality, belongingness, and oneness. If color induces wholeness, it can also induce fragmentation. Therefore, in order to understand the role played by color within the process of part-whole organization, color is used both as a wholeness and as a fragmentation tool, thus operating synergistically or antagonistically with other wholeness processes. Therefore, color is expected to influence figure-ground segregation, grouping, shape formation and other visual processes that are related to the phenomenal wholeness. The purpose of this study is to rate the influence of color in inducing whole and part-whole organization and, consequently, in determining the perception of figure-ground segregation, grouping, shape formation, numerousness evaluation and time reading. We manipulated experimental conditions by using equiluminant colors to favor or break (parcel-out) the wholeness of objects like geometrical composite figures and words. The results demonstrated that color is aimed, among other psychological and biological purposes, at: (1) relating each chromatic component of an object, thus favoring the emergence of the whole object; (2) eliciting a part-whole organization, whose components are interdependent; (3) eliciting fragments and then breaking up the whole and favoring the emergence of single components. Wholeness, part-whole organization and fragmentation can be considered as three further purposes of color. © 2010 The Authors, Ophthalmic and Physiological Optics © 2010 The College of Optometrists.

  17. Role of computers in quality assurance in the LLL Criticality Safety Program

    International Nuclear Information System (INIS)

    Koponen, B.L.

    1978-01-01

    Some of the aspects of computational criticality safety quality assurance that have been emphasized in recent years at LLL are summarized. In particular, computer code changes that have been made that help the criticality analyst reduce the number of errors that he makes and to locate those that he does make; and how a computerized ''benchmark'' data base aids him in the validation of his computational methods are discussed

  18. The role of backward associative strength in false recognition of DRM lists with multiple critical words.

    Science.gov (United States)

    Beato, María S; Arndt, Jason

    2017-08-01

    Memory is a reconstruction of the past and is prone to errors. One of the most widely-used paradigms to examine false memory is the Deese/Roediger-McDermott (DRM) paradigm. In this paradigm, participants studied words associatively related to a non-presented critical word. In a subsequent memory test critical words are often falsely recalled and/or recognized. In the present study, we examined the influence of backward associative strength (BAS) on false recognition using DRM lists with multiple critical words. In forty-eight English DRM lists, we manipulated BAS while controlling forward associative strength (FAS). Lists included four words (e.g., prison, convict, suspect, fugitive) simultaneously associated with two critical words (e.g., CRIMINAL, JAIL). The results indicated that true recognition was similar in high-BAS and low-BAS lists, while false recognition was greater in high-BAS lists than in low-BAS lists. Furthermore, there was a positive correlation between false recognition and the probability of a resonant connection between the studied words and their associates. These findings suggest that BAS and resonant connections influence false recognition, and extend prior research using DRM lists associated with a single critical word to studies of DRM lists associated with multiple critical words.

  19. Resilience? Insights into the role of Critical Infrastructures Disaster Mitigation Strategies

    Directory of Open Access Journals (Sweden)

    Sara Bouchon

    2012-11-01

    Full Text Available Critical infrastructures (CI systems provide essential services “for the maintenance of critical societal functions, including the supply chain, health, safety, security and economic or social well-being of the people” (European Commission, 2008. These systems are exposed to a great number of hazards and threats, which may result in severe consequences for the population, the socio-economic system, and the environment. The issue is particularly relevant at urban level, where the disruption of one CI system can propagate to the other systems and paralyze the entire area. It is therefore necessary, not only to protect CIs through Critical Infrastructure Protection (CIP strategies, but also to enhance the resilience of these areas. This article aims thus at providing some insights related to the evolution of the critical infrastructures disaster mitigation strategies from the sole protection towards resilience: what kind of strategies based on resilience can be developed to address CIs disruption at local or regional level? To what extent do these strategies contribute to increase the resilience level of the entire urban or metropolitan area? The first section focuses on the urban critical infrastructures systems as well as on the way their disruption can impact urban areas. The second section provides with some examples of key measures to operationalize resilience in the field of critical infrastructure disaster mitigation strategies. The last section highlights how the key measures developed to enhance the resilience against CI disruptions can benefit also to broader urban resilience. 

  20. The role of minimum supply and social vulnerability assessment for governing critical infrastructure failure: current gaps and future agenda

    Directory of Open Access Journals (Sweden)

    M. Garschagen

    2018-04-01

    Full Text Available Increased attention has lately been given to the resilience of critical infrastructure in the context of natural hazards and disasters. The major focus therein is on the sensitivity of critical infrastructure technologies and their management contingencies. However, strikingly little attention has been given to assessing and mitigating social vulnerabilities towards the failure of critical infrastructure and to the development, design and implementation of minimum supply standards in situations of major infrastructure failure. Addressing this gap and contributing to a more integrative perspective on critical infrastructure resilience is the objective of this paper. It asks which role social vulnerability assessments and minimum supply considerations can, should and do – or do not – play for the management and governance of critical infrastructure failure. In its first part, the paper provides a structured review on achievements and remaining gaps in the management of critical infrastructure and the understanding of social vulnerabilities towards disaster-related infrastructure failures. Special attention is given to the current state of minimum supply concepts with a regional focus on policies in Germany and the EU. In its second part, the paper then responds to the identified gaps by developing a heuristic model on the linkages of critical infrastructure management, social vulnerability and minimum supply. This framework helps to inform a vision of a future research agenda, which is presented in the paper's third part. Overall, the analysis suggests that the assessment of socially differentiated vulnerabilities towards critical infrastructure failure needs to be undertaken more stringently to inform the scientifically and politically difficult debate about minimum supply standards and the shared responsibilities for securing them.

  1. The role of minimum supply and social vulnerability assessment for governing critical infrastructure failure: current gaps and future agenda

    Science.gov (United States)

    Garschagen, Matthias; Sandholz, Simone

    2018-04-01

    Increased attention has lately been given to the resilience of critical infrastructure in the context of natural hazards and disasters. The major focus therein is on the sensitivity of critical infrastructure technologies and their management contingencies. However, strikingly little attention has been given to assessing and mitigating social vulnerabilities towards the failure of critical infrastructure and to the development, design and implementation of minimum supply standards in situations of major infrastructure failure. Addressing this gap and contributing to a more integrative perspective on critical infrastructure resilience is the objective of this paper. It asks which role social vulnerability assessments and minimum supply considerations can, should and do - or do not - play for the management and governance of critical infrastructure failure. In its first part, the paper provides a structured review on achievements and remaining gaps in the management of critical infrastructure and the understanding of social vulnerabilities towards disaster-related infrastructure failures. Special attention is given to the current state of minimum supply concepts with a regional focus on policies in Germany and the EU. In its second part, the paper then responds to the identified gaps by developing a heuristic model on the linkages of critical infrastructure management, social vulnerability and minimum supply. This framework helps to inform a vision of a future research agenda, which is presented in the paper's third part. Overall, the analysis suggests that the assessment of socially differentiated vulnerabilities towards critical infrastructure failure needs to be undertaken more stringently to inform the scientifically and politically difficult debate about minimum supply standards and the shared responsibilities for securing them.

  2. Mediating role of critical thinking disposition in the relationship between perceived barriers to research use and evidence-based practice.

    Science.gov (United States)

    Kim, Sun-Ae; Song, Youngshin; Sim, Hee-Sook; Ahn, Eun-Kyong; Kim, Jung-Hee

    2015-01-01

    Despite the importance of critical thinking in clinical and educational settings, little is known about its role in evidence-based practice (EBP). This study examined whether critical thinking disposition (CTD) mediates the relationship between perceived barriers to research use and EBP in clinical nurses (N=409). A path diagram using structural equation modeling was used to estimate the direct and indirect effects of perceived barriers to research use on EBP, controlling for CTD as a mediator. CTD partially mediated the relationship between perceived barriers to research use and EBP. Furthermore, the hypothesized mediation model demonstrated an appropriate fit to the data. Individual and organizational efforts are needed to help nurses further improve their critical thinking skills. CTD is important as research barriers to engage effectively in EBP. Without the skills to evaluate evidence carefully, research utilization may be compromised.

  3. Serbian music criticism in the first half of the twentieth century: Its canon, its method and its educational role

    Directory of Open Access Journals (Sweden)

    Vasić Aleksandar

    2008-01-01

    Full Text Available Serbian music criticism became a subject of professional music critics at the beginning of the twentieth century, after being developed by music amateurs throughout the whole previous century. The Serbian Literary Magazine (1901- 1914, 1920-1941, the forum of the Serbian modernist writers in the early 1900s, had a crucial role in shaping the Serbian music criticism and essayistics of the modern era. The Serbian elite musicians wrote for the SLM and therefore it reflects the most important issues of the early twentieth century Serbian music. The SLM undertook the mission of educating its readers. The music culture of the Serbian public was only recently developed. The public needed an introduction into the most important features of the European music, as well as developing its own taste in music. This paper deals with two aspects of the music criticism in the SLM, in view of its educational role: the problem of virtuosity and the method used by music critics in this magazine. The aesthetic canon of the SLM was marked by decisively negative attitude towards the virtuosity. Mainly concerned by educating the Serbian music public in the spirit of the highest music achievements in Europe, the music writers of the SLM criticized both domestic and foreign performers who favoured virtuosity over the 'essence' of music. Therefore, Niccolò Paganini, Franz Liszt, and even Peter Tchaikowsky with his Violin concerto became the subject of the magazine's criticism. However their attitude towards the interpreters with both musicality and virtuoso technique was always positive. That was evident in the writings on Jan Kubelík. This educational mission also had its effect on the structure of critique writings in the SLM. In their wish to inform the Serbian public on the European music (which they did very professionally, the critics gave much more information on biographies, bibliographies and style of the European composers, than they valued the interpretation

  4. The mediating role of self-criticism and dependency in the association between perceptions of maternal caring and depressive symptoms.

    Science.gov (United States)

    Campos, Rui C; Besser, Avi; Blatt, Sidney J

    2010-12-01

    This study examined a theoretically based mediation model including participants' perceptions of early relationships with their mother, self-criticism, dependency, and current depressive symptoms. We expect that (a) early relationships characterized by low levels of care and high levels of overprotection will be positively associated with both current depressive state and self-criticism and dependency; (b) high levels of self-criticism and dependency will be positively associated with depressive symptoms; and (c) self-criticism and dependency will play a mediating role in the association between participants' perceptions of early relationships characterized by low levels of care and high levels of overprotection and their current depressive symptoms. A nonclinical community sample of 200 Portuguese adults participated in the study. Perceptions of early relationships were measured using the mother scales of the Parental Bonding Instrument (Parker et al. [1979: Br J Med Psychol 52:1-10]), levels of self-criticism and dependency were measured using the Depressive Experiences Questionnaire (Blatt et al. [1976: J Abn Psy 6:383-389]), and depressive symptoms were measured using the Center for the Epidemiological Studies of Depression Scale (Radloff [1977: Appl Psychol Meas 1:385-401]. Structural equation modeling showed that the link between participants' perceptions of early caretaking relationships with their mothers and their current depressive symptoms is mediated by high levels of self-criticism--a personality trait associated with vulnerability to depression--but not Dependency. However, an ancillary analysis indicated that the link between participants' perceptions of early maternal overprotective relationships and their current depressive symptoms is mediated by high levels of Neediness. Findings underscore the role of perceived early relationships in psychological vulnerability to depression among highly self-critical and among highly needy individuals and

  5. When Mergers Fail: A Case Study on the Critical Role of External Stakeholders in Merger Initiatives

    Science.gov (United States)

    Stensaker, Bjørn; Persson, Mats; Pinheiro, Rómulo

    2016-01-01

    One can, in principle, identify numerous arguments for mergers in higher education (HE), including efficiency, diversity, quality, and regional needs. This diversity can be explained by the growing societal interest in the sector, not least concerning the contributions from HE to society at large. However, research on merger processes has tended…

  6. Disordered eating and suicidal intent: the role of thin ideal internalisation, shame and family criticism.

    Science.gov (United States)

    Unikel, C; Von Holle, A; Bulik, C M; Ocampo, R

    2012-01-01

    We explored the effect of thin ideal internalisation, shame proneness and family criticism on disordered eating and suicidal intent in female Mexican adolescents. We studied a probabilistic sample of 2537 high school students in central Mexico, stratified by marginalisation status and migratory intensity. We used a generalised logistic regression model to estimate the odds of disordered eating and suicidal intent across scores for three predictors: Internalisation of the thin ideal, shame and family criticism. Disordered eating was reported by 4.2% (95% CI = 0.9-7.5%) and suicidal intent by 13.2% (95% CI = 12.0-14.4%) of girls. The unadjusted odds ratios of any disordered eating for thin ideal internalisation, shame proneness and familial criticism were 1.2, 1.1 and 3.2, respectively. The positive association between thin ideal internalisation and disordered eating remained even after controlling for shame proneness and familial criticism. The association of these variables with suicidal intent was weaker. Results support stronger effects for disordered eating than suicidal intent across the three unadjusted predictors. It also highlights the presence of the relationship of criticism and disordered eating in female adolescents from low and middle socio-economic backgrounds. Copyright © 2010 John Wiley & Sons, Ltd. and Eating Disorders Association.

  7. Role of experimental resolution in measurements of critical layer thickness for strained-layer epitaxy

    International Nuclear Information System (INIS)

    Fritz, I.J.

    1987-01-01

    Experimental measurements of critical layer thicknesses (CLT's) in strained-layer epitaxy are considered. Finite experimental resolution can have a major effect on measured CLT's and can easily lead to spurious results. The theoretical approach to critical layer thicknesses of J. W. Matthews [J. Vac. Sci. Technol. 12, 126 (1975)] has been modified in a straightforward way to predict the apparent critical thickness for an experiment with finite resolution in lattice parameter. The theory has also been modified to account for the general empirical result that fewer misfit dislocations are generated than predicted by equilibrium calculation. The resulting expression is fit to recent x-ray diffraction data on InGaAs/GaAs and SiGe/Si. The results suggest that CLT's in these systems may not be significantly larger than predicted by equilibrium theory, in agreement with high-resolution measurements

  8. Canine Distemper Virus Fusion Activation: Critical Role of Residue E123 of CD150/SLAM.

    Science.gov (United States)

    Khosravi, Mojtaba; Bringolf, Fanny; Röthlisberger, Silvan; Bieringer, Maria; Schneider-Schaulies, Jürgen; Zurbriggen, Andreas; Origgi, Francesco; Plattet, Philippe

    2016-02-01

    Measles virus (MeV) and canine distemper virus (CDV) possess tetrameric attachment proteins (H) and trimeric fusion proteins, which cooperate with either SLAM or nectin 4 receptors to trigger membrane fusion for cell entry. While the MeV H-SLAM cocrystal structure revealed the binding interface, two distinct oligomeric H assemblies were also determined. In one of the conformations, two SLAM units were sandwiched between two discrete H head domains, thus spotlighting two binding interfaces ("front" and "back"). Here, we investigated the functional relevance of both interfaces in activating the CDV membrane fusion machinery. While alanine-scanning mutagenesis identified five critical regulatory residues in the front H-binding site of SLAM, the replacement of a conserved glutamate residue (E at position 123, replaced with A [E123A]) led to the most pronounced impact on fusion promotion. Intriguingly, while determination of the interaction of H with the receptor using soluble constructs revealed reduced binding for the identified SLAM mutants, no effect was recorded when physical interaction was investigated with the full-length counterparts of both molecules. Conversely, although mutagenesis of three strategically selected residues within the back H-binding site of SLAM did not substantially affect fusion triggering, nevertheless, the mutants weakened the H-SLAM interaction recorded with the membrane-anchored protein constructs. Collectively, our findings support a mode of binding between the attachment protein and the V domain of SLAM that is common to all morbilliviruses and suggest a major role of the SLAM residue E123, located at the front H-binding site, in triggering the fusion machinery. However, our data additionally support the hypothesis that other microdomain(s) of both glycoproteins (including the back H-binding site) might be required to achieve fully productive H-SLAM interactions. A complete understanding of the measles virus and canine distemper virus

  9. Specifying a curriculum for biopolitical critical literacy in science teacher education: exploring roles for science fiction

    Science.gov (United States)

    Gough, Noel

    2017-12-01

    In this essay I suggest some ways in which science teacher educators in Western neoliberal economies might facilitate learners' development of a critical literacy concerning the social and cultural changes signified by the concept of biopolitics. I consider how such a biopolitically inflected critical literacy might find expression in a science teacher education curriculum and suggest a number of ways of materializing such a curriculum in specific literatures, media, procedures, and assessment tasks, with particular reference to the contributions of science fiction in popular media.

  10. The role of nutritional support in the physical and functional recovery of critically ill patients: a narrative review.

    Science.gov (United States)

    Bear, Danielle E; Wandrag, Liesl; Merriweather, Judith L; Connolly, Bronwen; Hart, Nicholas; Grocott, Michael P W

    2017-08-26

    The lack of benefit from randomised controlled trials has resulted in significant controversy regarding the role of nutrition during critical illness in terms of long-term recovery and outcome. Although methodological caveats with a failure to adequately appreciate biological mechanisms may explain these disappointing results, it must be acknowledged that nutritional support during early critical illness, when considered alone, may have limited long-term functional impact.This narrative review focuses specifically on recent clinical trials and evaluates the impact of nutrition during critical illness on long-term physical and functional recovery.Specific focus on the trial design and methodological limitations has been considered in detail. Limitations include delivery of caloric and protein targets, patient heterogeneity, short duration of intervention, inappropriate clinical outcomes and a disregard for baseline nutritional status and nutritional intake in the post-ICU period.With survivorship at the forefront of critical care research, it is imperative that nutrition studies carefully consider biological mechanisms and trial design because these factors can strongly influence outcomes, in particular long-term physical and functional outcome. Failure to do so may lead to inconclusive clinical trials and consequent rejection of the potentially beneficial effects of nutrition interventions during critical illness.

  11. The Role of Gender in Workplace Stress: A Critical Literature Review

    Science.gov (United States)

    Gyllensten, Kristina; Palmer, Stephen

    2005-01-01

    Objective: The aim of this review was to evaluate research relating to the role of gender in the level of workplace stress. A further aim was to review literature relating to stressors of particular relevance to working women. These stressors included, multiple roles, lack of career progress and discrimination and stereotyping. Design: Systematic…

  12. Critical role of aldehydes in cigarette smoke-induced acute airway inflammation

    NARCIS (Netherlands)

    van der Toorn, Marco; Slebos, Dirk-Jan; de Bruin, Harold G.; Gras, Renee; Rezayat, Delaram; Jorge, Lucie; Sandra, Koen; van Oosterhout, Antoon J. M.

    2013-01-01

    Background: Cigarette smoking (CS) is the most important risk factor for COPD, which is associated with neutrophilic airway inflammation. We hypothesize, that highly reactive aldehydes are critical for CS-induced neutrophilic airway inflammation. Methods: BALB/c mice were exposed to CS, water

  13. Sleep to be social: The critical role of sleep and memory for social interaction.

    Science.gov (United States)

    Diekelmann, Susanne; Paulus, Frieder M; Krach, Sören

    2018-01-01

    Humans are highly social animals who critically need to remember information from social episodes in order to successfully navigate future social interactions. We propose that such episodic memories about social encounters are processed during sleep, following the learning experience, with sleep abstracting and consolidating social gist knowledge (e.g., beliefs, first impressions, or stereotypes) about others that supports relationships and interpersonal communication.

  14. Calculations of critical micelle concentration by dissipative particle dynamics simulations: the role of chain rigidity.

    Science.gov (United States)

    Lee, Ming-Tsung; Vishnyakov, Aleksey; Neimark, Alexander V

    2013-09-05

    Micelle formation in surfactant solutions is a self-assembly process governed by complex interplay of solvent-mediated interactions between hydrophilic and hydrophobic groups, which are commonly called heads and tails. However, the head-tail repulsion is not the only factor affecting the micelle formation. For the first time, we present a systematic study of the effect of chain rigidity on critical micelle concentration and micelle size, which is performed with the dissipative particle dynamics simulation method. Rigidity of the coarse-grained surfactant molecule was controlled by the harmonic bonds set between the second-neighbor beads. Compared to flexible molecules with the nearest-neighbor bonds being the only type of bonded interactions, rigid molecules exhibited a lower critical micelle concentration and formed larger and better-defined micelles. By varying the strength of head-tail repulsion and the chain rigidity, we constructed two-dimensional diagrams presenting how the critical micelle concentration and aggregation number depend on these parameters. We found that the solutions of flexible and rigid molecules that exhibited approximately the same critical micelle concentration could differ substantially in the micelle size and shape depending on the chain rigidity. With the increase of surfactant concentration, primary micelles of more rigid molecules were found less keen to agglomeration and formation of nonspherical aggregates characteristic of flexible molecules.

  15. The Role of Critical Thinking in Reader Perceptions of Leadership in Comic Books

    Science.gov (United States)

    Krusemark, Renee

    2015-01-01

    This study qualitatively explored how readers use critical thinking to perceive leadership in "The Walking Dead" comic books. Sixty-nine participants gave responses regarding their thoughts about leadership in the comic via an online survey. A majority of the participants indicated a wide range of values for comics as a learning…

  16. The critical role of ocean container transport in global supply chain performance

    NARCIS (Netherlands)

    Fransoo, J.C.; Lee, C.Y.

    2013-01-01

    With supply chains distributed across global markets, ocean container transport now is a critical element of any such supply chain. We identify key characteristics of ocean container transport from a supply chain perspective. We find that unlike continental (road) transport, service offerings tend

  17. The Role and Impact of Critical Review as Perceived by an Implementer

    International Nuclear Information System (INIS)

    Thegerstroem, Claes; Laarouchi Engstroem, Saida; Olsson, Olle

    2006-01-01

    The quality and success of a nuclear waste management programme is based on the amalgamation of the interests of a wide number of stakeholders, integration of many different scientific disciplines, and merging of scientific, technical, ethical and social issues. In this process, a broad and structured review of all aspects of the program is necessary and we find the process with submission and review by stakeholders, regulators and government every third year very useful. High-quality critical review of is always a real benefit to the implementer - as it gives the implementer the possibility to see where improvements can be made. However, a close dialogue and a dynamic reviewing process, where questions are raised throughout the process, are essential in order to optimize the quality of the final applications. Naturally, critical review should not be used for pushing specific general research interests or issues that belong to the political arena rather than nuclear waste management itself. Moreover, critical review provides additional insight and promotes confidence by the general public. However, sometimes the public might be confused and have difficulties in judging the importance and relevance of critical comments. The implementer and regulatory authorities have a special duty to provide an overall perspective of safety-related issues. Even if critical review is valuable, the implementer can not only rely on this. The implementers' own internal quality assurance practise, internal review process as well as its overall safety culture is all crucial. Indeed, a successful management of radio-active waste, including operational aspects as well as siting process, starts with the implementers' own wish to perform state-of-the art-work both in terms of technology and overall approach

  18. The Role and Impact of Critical Review as Perceived by an Implementer

    Energy Technology Data Exchange (ETDEWEB)

    Thegerstroem, Claes; Laarouchi Engstroem, Saida; Olsson, Olle [Swedish Nuclear Fuel and Waste Management Co, Stockholm (Sweden)

    2006-09-15

    The quality and success of a nuclear waste management programme is based on the amalgamation of the interests of a wide number of stakeholders, integration of many different scientific disciplines, and merging of scientific, technical, ethical and social issues. In this process, a broad and structured review of all aspects of the program is necessary and we find the process with submission and review by stakeholders, regulators and government every third year very useful. High-quality critical review of is always a real benefit to the implementer - as it gives the implementer the possibility to see where improvements can be made. However, a close dialogue and a dynamic reviewing process, where questions are raised throughout the process, are essential in order to optimize the quality of the final applications. Naturally, critical review should not be used for pushing specific general research interests or issues that belong to the political arena rather than nuclear waste management itself. Moreover, critical review provides additional insight and promotes confidence by the general public. However, sometimes the public might be confused and have difficulties in judging the importance and relevance of critical comments. The implementer and regulatory authorities have a special duty to provide an overall perspective of safety-related issues. Even if critical review is valuable, the implementer can not only rely on this. The implementers' own internal quality assurance practise, internal review process as well as its overall safety culture is all crucial. Indeed, a successful management of radio-active waste, including operational aspects as well as siting process, starts with the implementers' own wish to perform state-of-the art-work both in terms of technology and overall approach.

  19. A critical assessment on the role of sentinel node mapping in endometrial cancer.

    Science.gov (United States)

    Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Perotto, Stefania; Lorusso, Domenica; Raspagliesi, Francesco

    2015-10-01

    Endometrial cancer is the most common gynecologic malignancy in the developed countries. Although the high incidence of this occurrence no consensus, about the role of retroperitoneal staging, still exists. Growing evidence support the safety and efficacy of sentinel lymph node mapping. This technique is emerging as a new standard for endometrial cancer staging procedures. In the present paper, we discuss the role of sentinel lymph node mapping in endometrial cancer, highlighting the most controversies features.

  20. A critical consideration of the role of social networks in the Arab spring

    OpenAIRE

    Kragović Branislava B.

    2013-01-01

    Mass media play a role in social changes by influencing the public opinion during phases of preparation, implementation and justification of performed changes. Social changes in the global age, especially those of greater scope, are hardly imaginable without the role of mass media. Mass media as an instrument of influence over public opinion is used in both cases - when a change goes from 'down' or from 'up'. With regards to the changes initiated by the power holders, the means of impact usua...

  1. Role of Serum Iron in the Activation of Lipid Peroxidation in Critical Conditions

    Directory of Open Access Journals (Sweden)

    Yu. P. Orlov

    2006-01-01

    Full Text Available Twenty-four critically ill patients due to generalized purulent peritonitis, pancreatonecrosis, thermal skin injuries, and severe poisoning by acetic acid were examined. The general regularities of the effect of high serum iron concentrations on the health status of patients, on the activity of antioxidative enzymes, and on the initiation of lipid peroxidation (LPO processes, as supported by the values of Fe2+-induced chemiluminescence, were revealed. In critically ill patients, iron metabolism occurs with the overload of a transport protein, such as transferrin, which is caused by intravascular hemolysis and hemoglobin metabolism to ionized iron. The overload of proteins responsible for iron transport leads to the tissue accumulation of free (ferrous and ferric iron that is actively involved in the processes of LPO initiation with excess synthesis of cytotoxic radicals, which in turn accounts for the severity of endotoxicosis.

  2. The Role of Time-Limited Trials in Dialysis Decision Making in Critically Ill Patients.

    Science.gov (United States)

    Scherer, Jennifer S; Holley, Jean L

    2016-02-05

    Technologic advances, such as continuous RRT, provide lifesaving therapy for many patients. AKI in the critically ill patient, a fatal diagnosis in the past, is now often a survivable condition. Dialysis decision making for the critically ill patient with AKI is complex. What was once a question solely of survival now is nuanced by an individual's definition of quality of life, personal values, and short- and long-term prognoses. Clinical evaluation of AKI in the critically ill is multifaceted. Treatment decision making requires consideration of the natural evolution of the patient's AKI within the context of the global prognosis. Situations are often marked by prognostic uncertainty and clinical unknowns. In the face of these uncertainties, establishment of patient-directed therapies is imperative. A time-limited trial of continuous RRT in this setting is often appropriate but difficult to execute. Using patient preferences as a clinical guide, a proper time-limited trial requires assessment of prognosis, elicitation of patient values, strong communication skills, clear documentation, and often, appropriate integration of palliative care services. A well conducted time-limited trial can avoid interprofessional conflict and provide support for the patient, family, and staff. Copyright © 2016 by the American Society of Nephrology.

  3. The views of key leaders in South Africa on implementation of family medicine: critical role in the district health system.

    Science.gov (United States)

    Moosa, Shabir; Mash, Bob; Derese, Anselme; Peersman, Wim

    2014-06-25

    Integrated team-based primary care is an international imperative. This is required more so in Africa, where fragmented verticalised care dominates. South Africa is trying to address this with health reforms, including Primary Health Care Re-engineering. Family physicians are already contributing to primary care despite family medicine being only fully registered as a full specialty in South Africa in 2008. However the views of leaders on family medicine and the role of family physicians is not clear, especially with recent health reforms. The aim of this study was to understand the views of key government and academic leaders in South Africa on family medicine, roles of family physicians and human resource issues. This was a qualitative study with academic and government leaders across South Africa. In-depth interviews were conducted with sixteen purposively selected leaders using an interview guide. Thematic content analysis was based on the framework method. Whilst family physicians were seen as critical to the district health system there was ambivalence on their leadership role and 'specialist' status. National health reforms were creating both threats and opportunities for family medicine. Three key roles for family physicians emerged: supporting referrals; clinical governance/quality improvement; and providing support to community-oriented care. Respondents' urged family physicians to consolidate the development and training of family physicians, and shape human resource policy to include family physicians. Family physicians were seen as critical to the district health system in South Africa despite difficulties around their precise role. Whilst their role was dominated by filling gaps at district hospitals to reduce referrals it extended to clinical governance and developing community-oriented primary care - a tall order, requiring strong teamwork. Innovative team-based service delivery is possible despite human resource challenges, but requires family

  4. Evaluating the roles and competencies that are critical considerations for management development

    Directory of Open Access Journals (Sweden)

    Patsy Govender

    2010-06-01

    Research purpose: This study assesses the extent to which the current management cadre in a public sector division possesses the eight managerial roles/competencies (mentor, facilitator, monitor, co-ordinator, director, producer, broker, innovator needed for effective management with the aim of identifying areas for management development. It also aims to assess whether the managerial roles relate to each other. Motivation for the study: In order to avoid a ‘hit and miss’ approach to management development it is important to assess managerial roles/competencies to effectively identify areas for enhancement. Research design, approach and method: The empirical analysis entailed data collection through the use of questionnaires, administered to a sample of 202 from a population of 400 managers, drawn using the stratified random sampling technique, thereby generating a 51% response rate. Data were analysed using descriptive and inferential statistics. Main findings: The results indicate that managers in this public sector division are fulfilling the managerial roles in varying degrees, though not optimally. They do not display optimal paradoxical capability and behaviour complexity. Furthermore, the eight roles/competencies are interconnected. Managerial level, age and race were found to influence the extent to which managers possess and display various competencies. Practical/managerial implications: The interconnectedness of the managerial roles/competencies implies that effective leaders should be ambidextrous in a figurative sense. Based on the results, a framework is generated that identifies areas for improvement in the managerial competencies required to ensure managerial effectiveness and hence presents skills to be developed or areas for management development in order to enhance each managerial role. Contribution/value-add: The need for managers to be able to display optimal paradoxical capabilities and behavioural complexities is becoming more and more

  5. Critical role of cerebellar fastigial nucleus in programming sequences of saccades

    Science.gov (United States)

    King, Susan A.; Schneider, Rosalyn M.; Serra, Alessandro; Leigh, R. John

    2011-01-01

    The cerebellum plays an important role in programming accurate saccades. Cerebellar lesions affecting the ocular motor region of the fastigial nucleus (FOR) cause saccadic hypermetria; however, if a second target is presented before a saccade can be initiated (double-step paradigm), saccade hypermetria may be decreased. We tested the hypothesis that the cerebellum, especially FOR, plays a pivotal role in programming sequences of saccades. We studied patients with saccadic hypermetria due either to genetic cerebellar ataxia or surgical lesions affecting FOR and confirmed that the gain of initial saccades made to double-step stimuli was reduced compared with the gain of saccades to single target jumps. Based on measurements of the intersaccadic interval, we found that the ability to perform parallel processing of saccades was reduced or absent in all of our patients with cerebellar disease. Our results support the crucial role of the cerebellum, especially FOR, in programming sequences of saccades. PMID:21950988

  6. Macrophage Migration Inhibitory Factor: Critical Role in Obesity, Insulin Resistance, and Associated Comorbidities

    Directory of Open Access Journals (Sweden)

    Robert Kleemann

    2010-01-01

    Full Text Available Obesity is associated with insulin resistance, disturbed glucose homeostasis, low grade inflammation, and comorbidities such as type 2 diabetes and cardiovascular disease. The cytokine macrophage migration inhibitory factor (MIF is an ubiquitously expressed protein that plays a crucial role in many inflammatory and autoimmune disorders. Increasing evidence suggests that MIF also controls metabolic and inflammatory processes underlying the development of metabolic pathologies associated with obesity. This is a comprehensive summary of our current knowledge on the role of MIF in obesity and obesity-associated comorbidities, based on human clinical data as well as animal models of disease.

  7. Evaluating the roles and competencies that are critical considerations for management development

    Directory of Open Access Journals (Sweden)

    Patsy Govender

    2010-03-01

    Full Text Available Orientation: If managerial roles/competencies are evaluated in an organisation, shortfalls in managerial functions can serve as areas for management development thereby enabling the potential to create master managers.Research purpose: This study assesses the extent to which the current management cadre in a public sector division possesses the eight managerial roles/competencies (mentor, facilitator, monitor, co-ordinator, director, producer, broker, innovator needed for effective management with the aim of identifying areas for management development. It also aims to assess whether the managerial roles relate to each other.Motivation for the study: In order to avoid a ‘hit and miss’ approach to management development it is important to assess managerial roles/competencies to effectively identify areas for enhancement.Research design, approach and method: The empirical analysis entailed data collection through the use of questionnaires, administered to a sample of 202 from a population of 400 managers, drawn using the stratified random sampling technique, thereby generating a 51% response rate. Data were analysed using descriptive and inferential statistics.Main findings: The results indicate that managers in this public sector division are fulfilling the managerial roles in varying degrees, though not optimally. They do not display optimal paradoxical capability and behaviour complexity. Furthermore, the eight roles/competencies are interconnected. Managerial level, age and race were found to influence the extent to which managers possess and display various competencies.Practical/managerial implications: The interconnectedness of the managerial roles/competencies implies that effective leaders should be ambidextrous in a figurative sense. Based on the results, a framework is generated that identifies areas for improvement in the managerial competencies required to ensure managerial effectiveness and hence presents skills to be developed

  8. A critical consideration of the role of social networks in the Arab spring

    Directory of Open Access Journals (Sweden)

    Kragović Branislava B.

    2013-01-01

    Full Text Available Mass media play a role in social changes by influencing the public opinion during phases of preparation, implementation and justification of performed changes. Social changes in the global age, especially those of greater scope, are hardly imaginable without the role of mass media. Mass media as an instrument of influence over public opinion is used in both cases - when a change goes from 'down' or from 'up'. With regards to the changes initiated by the power holders, the means of impact usually used are classic mass media-newspapers, radio, television, and more often, Internet. However, in cases when the initiators of changes are on lower levels of social hierarchy, the first choice is Internet due to its accessibility and decentralized structure. Internet had demonstrated its influence on social changes earlier, but that influence was especially visible during the 'Arab spring'. The 'Arab spring' is a collective name for a wave of protests and changes which sparked in Tunisia in December 2010 and spilled over to other countries of the northern Africa and Near East. Egypt, Syria, Bahrain, Sudan, Libya, Morocco, Yemen, Algeria are some of them. Due to their prominent role in dissemination of information, the Tunisian episode of the 'Arab spring' is called Facebook revolution or Internet revolution, which clearly indicates which media and social networks had played key role in change of government in Tunisia. Mobile phone, being media of interpersonal communication, have also played significant role in case of Tunisia, the same role mass media had in changes of real-socialist systems. Development of new technologies and their application in field of communication means have revolutionized the communication process. Naturally, television has also played its role in the 'Arab spring'. Bearing in mind that national media services are mostly controlled by the governing elite, the news on rebellion in Tunisia were spread through global media

  9. Understanding ironic criticism and empathic praise: The role of emotive communication.

    Science.gov (United States)

    Agostino, Alba; Im-Bolter, Nancie; Stefanatos, Arianna K; Dennis, Maureen

    2017-06-01

    Ironic criticism and empathic praise are forms of social communication that influence the affective states of others in a negative or positive way. In a sample of 76 typically developing children and adolescents (mean age = 11 years; 4 months; SD: 2 years; 8 months), we studied how understanding of emotional expression (facial expression of emotion) and emotive communication (affective theory of mind) was related to the ability to understand negatively valenced ironic criticism and positively valenced empathic praise. We modelled comprehension of irony and empathy in school-aged children in relation to age and understanding of emotional expression and emotive communication. As expected, children showed significantly better understanding of emotional expression than emotive communication, which requires understanding why someone might mask their inner emotions. Meditational analyses showed that emotive communication partially mediated the relation between age and understanding ironic criticism and empathic praise. These findings suggest that the development of understanding irony and empathy over the school-age years is associated with affective attributions or affective theory of mind. Statement of contribution What is already known on this subject? Theory of mind has been found to be related to the developmental understanding of social communication. Correct interpretation of facial emotional cues is also important for interpreting social communication. What does this study add? Affective components (i.e., affective theory of mind) also contribute to the development of social communication. Emotive communication, the ability to modulate one's emotional expression according to social display rules may be predictive of social communication competency. © 2016 The British Psychological Society.

  10. Present knowledge and perspectives on the role of copper in brake materials and related environmental issues: A critical assessment.

    Science.gov (United States)

    Straffelini, Giovanni; Ciudin, Rodica; Ciotti, Alessandro; Gialanella, Stefano

    2015-12-01

    This critical review presents several aspects related to the use of copper as a main component in brake pads in road vehicles. The compositions of these materials are attracting increasing interest and concern due to the relative contribution of wear products to particulate matter emissions in the environment as a result of braking action even though there has been a reduction in exhaust products from internal combustion engines. We review the data on the main wear mechanisms in brake systems and highlight the positive role of copper. However, similar to other heavy metal emissions, even the release of copper into the atmosphere may have important environmental and health effects. Thus, several replacement strategies are being pursued, and the positive and negative features will be critically reviewed. Additionally, the future perspectives in materials development will be discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Nuclear alpha spectrin: Critical roles in DNA interstrand cross-link repair and genomic stability

    OpenAIRE

    Lambert, Muriel W

    2016-01-01

    Non-erythroid alpha spectrin (?IISp) is a structural protein which we have shown is present in the nucleus of human cells. It interacts with a number of nuclear proteins such as actin, lamin, emerin, chromatin remodeling factors, and DNA repair proteins. ?IISp?s interaction with DNA repair proteins has been extensively studied. We have demonstrated that nuclear ?IISp is critical in DNA interstrand cross-link (ICL) repair in S phase, in both genomic (non-telomeric) and telomeric DNA, and in ma...

  12. Role of disorder in the multi-critical region of d-wave superconductivity and antiferromagnetism

    International Nuclear Information System (INIS)

    Yanase, Youichi; Ogata, Masao

    2007-01-01

    We investigate the disorder-induced microscopic inhomogeneity in the multi-critical region of d-wave superconductivity and antiferromagnetism on the basis of the microscopic t-t ' -U-V model. We find that a small amount of point disorder induces the nano-scale inhomogeneity of spin and superconducting fluctuations when the coherence length of superconductivity is remarkably short as in the under-doped cuprates. Then, the two fluctuations spatially segregate to avoid their competition. We show the remarkable electron-hole asymmetry in high-T c cuprates where the quite different spatial structure is expected in the electron-doped materials

  13. The role of a critical ethnomathematics curriculum in transforming and empowering learners

    Directory of Open Access Journals (Sweden)

    Nirmala Naresh

    2015-07-01

    Full Text Available When thinking about mathematics, seldom does one think about culture, context, history, or diversity. Many teachers believe that there is no place for such constructs in their mathematics classrooms. As an ethnomathematician, my primary goal is to find meaningful ways to bring components of ethnomathematics into the mainstream mathematics curriculum and classrooms. In this paper, I describe key aspects of a mathematics curriculum that was designed to promote meaningful connections between ethnomathematics theory and practice and highlight how this curriculum might help address the key tenets of a critical ethnomathematics curriculum.

  14. Lysyl Oxidase Plays a Critical Role in Endothelial Cell Stimulation to Drive Tumor Angiogenesis

    DEFF Research Database (Denmark)

    Baker, Ann-Marie; Bird, Demelza; Welti, Jonathan C

    2013-01-01

    Identification of key molecules that drive angiogenesis is critical for the development of new modalities for the prevention of solid tumor progression. Using multiple models of colorectal cancer, we show that activity of the extracellular matrix-modifying enzyme lysyl oxidase (LOX) is essential...... for stimulating endothelial cells in vitro and angiogenesis in vivo. We show that LOX activates Akt through platelet-derived growth factor receptor ß (PDGFRß) stimulation, resulting in increased VEGF expression. LOX-driven angiogenesis can be abrogated through targeting LOX directly or using inhibitors of PDGFRß...

  15. Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.

    Science.gov (United States)

    Saroha, Ashish; Pewzner-Jung, Yael; Ferreira, Natalia S; Sharma, Piyush; Jouan, Youenn; Kelly, Samuel L; Feldmesser, Ester; Merrill, Alfred H; Trottein, François; Paget, Christophe; Lang, Karl S; Futerman, Anthony H

    2017-01-01

    The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T ( i NKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of i NKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of i NKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for i NKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in i NKT cell physiology.

  16. A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells

    Directory of Open Access Journals (Sweden)

    Stephanie Chrysanthou

    2018-04-01

    Full Text Available Summary: The ten-eleven translocation (TET proteins are well known for their role in maintaining naive pluripotency of embryonic stem cells. Here, we demonstrate that, jointly, TET1 and TET2 also safeguard the self-renewal potential of trophoblast stem cells (TSCs and have partially redundant roles in maintaining the epithelial integrity of TSCs. For the more abundantly expressed TET1, we show that this is achieved by binding to critical epithelial genes, notably E-cadherin, which becomes hyper-methylated and downregulated in the absence of TET1. The epithelial-to-mesenchymal transition phenotype of mutant TSCs is accompanied by centrosome duplication and separation defects. Moreover, we identify a role of TET1 in maintaining cyclin B1 stability, thereby acting as facilitator of mitotic cell-cycle progression. As a result, Tet1/2 mutant TSCs are prone to undergo endoreduplicative cell cycles leading to the formation of polyploid trophoblast giant cells. Taken together, our data reveal essential functions of TET proteins in the trophoblast lineage. : TET proteins are well known for their role in pluripotency. Here, Hemberger and colleagues show that TET1 and TET2 are also critical for maintaining the epithelial integrity of trophoblast stem cells. TET1/2 ensure mitotic cell-cycle progression by stabilizing cyclin B1 and by regulating centrosome organization. These insights reveal the importance of TET proteins beyond their role in epigenome remodeling. Keywords: TET proteins, trophoblast stem cells, cell cycle, endoreduplication, self-renewal, mitosis, trophoblast giant cells, differentiation

  17. Explaining Semantic Short-Term Memory Deficits: Evidence for the Critical Role of Semantic Control

    Science.gov (United States)

    Hoffman, Paul; Jefferies, Elizabeth; Lambon Ralph, Matthew A.

    2011-01-01

    Patients with apparently selective short-term memory (STM) deficits for semantic information have played an important role in developing multi-store theories of STM and challenge the idea that verbal STM is supported by maintaining activation in the language system. We propose that semantic STM deficits are not as selective as previously thought…

  18. Toward a new critical role of information systems in the modern ...

    African Journals Online (AJOL)

    pc

    2018-03-05

    Mar 5, 2018 ... this paper is to present the role of information systems in decision making management ... great impact on economic, social and culture aspects of life. Nowadays there are ... of activities such as accounting, selling, surveillance, etc. These ... The control function is the last stage which completes the cycle of ...

  19. Fungi Contribute Critical but Spatially Varying Roles in Nitrogen and Carbon Cycling in Acid Mine Drainage

    NARCIS (Netherlands)

    Mosier, Annika C; Miller, Christopher S; Frischkorn, Kyle R; Ohm, Robin A; Li, Zhou; LaButti, Kurt; Lapidus, Alla; Lipzen, Anna; Chen, Cindy; Johnson, Jenifer; Lindquist, Erika A; Pan, Chongle; Hettich, Robert L; Grigoriev, Igor V; Singer, Steven W; Banfield, Jillian F

    2016-01-01

    The ecosystem roles of fungi have been extensively studied by targeting one organism and/or biological process at a time, but the full metabolic potential of fungi has rarely been captured in an environmental context. We hypothesized that fungal genome sequences could be assembled directly from the

  20. Vitamin K’s role in age-related bone loss: A critical review

    Science.gov (United States)

    The protective role of vitamin K in age-related bone loss continues to be controversial. The results of observational analyses are inconsistent with respect to associations between vitamin K status and bone, which arguably may be related to the limitations of observational study designs and analyt...

  1. Lycopene and Its Antioxidant Role in the Prevention of Cardiovascular Diseases-A Critical Review.

    Science.gov (United States)

    Müller, Lars; Caris-Veyrat, Catherine; Lowe, Gordon; Böhm, Volker

    2016-08-17

    The present review is based mainly on papers published between 2000 and 2011 and gives information about the properties of the carotenoid lycopene in chemical and biological systems and its possible role in preventing cardiovascular diseases (CVD). The main aim of this report is to highlight its role as an antioxidant, also reported are bioactive properties that may influence the development of foam cells and protection against endothelial cell damage. The paper will also examine recent observations that lycopene may improve blood flow and reduce inflammatory responses. Lycopene possesses antioxidant properties in vitro, and some epidemiological studies have reported protective effects against the progression of CVD. The oxidation of human low density lipoproteins (LDL) is a fundamental mechanism in the initiation of atherosclerosis. A beneficial role of lycopene as antioxidant in the prevention of CVD is suggested but the data are still controversial. Lycopene is believed to be the most potent carotenoid antioxidant in vitro. Tissue culture experiments and animal studies support potential cardioprotective effects for lycopene and other carotenoids in the blood. Most studies showed beneficial effects of lycopene to individuals who are antioxidant-deficient like elderly patients, or humans exposed to higher levels of oxidative stress like smokers, diabetics, hemodialysis patients and acute myocardial infarction patients. By defining the right population and combining antioxidant potentials of lycopene with vitamins and other bioactive plant compounds, the beneficial role of lycopene in CVD can be clarified in future studies.

  2. Changing Lives? Critical Evaluation of a School-Based Athlete Role Model Intervention

    Science.gov (United States)

    Armour, Kathleen; Duncombe, Rebecca

    2012-01-01

    There would appear to be an enduring belief that successful sportsmen and women can act as powerful motivational role models for young people, especially disaffected, disadvantaged or disengaged youth. In the UK, for example, this belief has been expressed recently in the development of programmes, such as changingLIVES, the Respect Athlete Mentor…

  3. The Role of the Intellectual--An Excursion into Self-Criticism.

    Science.gov (United States)

    Galtung, Johan

    2002-01-01

    Distinguishes two roles of the intellectual, one in search of truth and the other in search of power. Sees the latter as closely related to the emergence of nation states and centralized capitalism and as problematic when it results in a small elite expropriating the challenges that should belong to others. (EV)

  4. Do critical care units play a role in the management of gynaecological oncology patients? The contribution of gynaecologic oncologist in running critical care units.

    Science.gov (United States)

    Davidovic-Grigoraki, Miona; Thomakos, Nikolaos; Haidopoulos, Dimitrios; Vlahos, Giorgos; Rodolakis, Alexandros

    2017-03-01

    Routine post-operative care in high dependency unit (HDU), surgical intensive care unit (SICU) and intensive care unit (ICU) after high-risk gynaecological oncology surgical procedures may allow for greater recognition and correct management of post-operative complications, thereby reducing long-term morbidity and mortality. On the other hand, unnecessary admissions to these units lead to increased morbidity - nosocomial infections, increased length of hospital stay and higher hospital costs. Gynaecological oncology surgeons continue to look after their patient in the HDU/SICU and have the final role in decision-making on day-to-day basis, making it important to be well versed in critical care management and ensure the best care for their patients. Post-operative monitoring and the presence of comorbid illnesses are the most common reasons for admission to the HDU/SICU. Elderly and malnutritioned patients, as well as, bowel resection, blood loss or greater fluid resuscitation during the surgery have prolonged HDU/SICU stay. Patients with ovarian cancer have a worse survival outcome than the patients with other types of gynaecological cancer. Dependency care is a part of surgical management and it should be incorporated formally into gynaecologic oncology training programme. © 2016 John Wiley & Sons Ltd.

  5. Hydrogeochemistry of prairie pothole region wetlands: Role of long-term critical zone processes

    Science.gov (United States)

    Goldhaber, Martin B.; Mills, Christopher T.; Morrison, Jean M.; Stricker, Craig A.; Mushet, David M.; LaBaugh, James W.

    2014-01-01

    This study addresses the geologic and hydrogeochemical processes operating at a range of scales within the prairie pothole region (PPR). The PPR is a 750,000 km2portion of north central North America that hosts millions of small wetlands known to be critical habitat for waterfowl and other wildlife. At a local scale, we characterized the geochemical evolution of the 92-ha Cottonwood Lake study area (CWLSA), located in North Dakota, USA. Critical zone processes are the long-term determinant of wetland water and groundwater geochemistry via the interaction of oxygenated groundwater with pyrite in the underlying glacial till. Pyrite oxidation produced a brown, iron oxide-bearing surface layer locally over 13 m thick and an estimated minimum of 1.3 × 1010 g sulfate (SO42 −) at CWLSA. We show that the majority of this SO42− now resides in solid-phase gypsum (CaSO4•2H2O) and gypsum-saturated groundwater.

  6. The potential role of nano- and micro-technology in the management of critical illnesses.

    Science.gov (United States)

    Sadikot, Ruxana T

    2014-11-20

    In recent years nanomedicine has become an attractive concept for the targeted delivery of therapeutic and diagnostic compounds to injured or inflamed organs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and increase the biodistribution of therapeutic agents to target organs, thereby resulting in improved efficacy and reduced drug toxicity. These systems are exploited for therapeutic purposes to carry the drug in the body in a controlled manner from the site of administration to the therapeutic target. The mortality in many of the critical illnesses such as sepsis and acute respiratory distress syndrome continues to remain high despite of an increased understanding of the molecular pathogenesis of these diseases. Several promising targets that have been identified as potential therapies for these devastating diseases have been limited because of difficulty with delivery systems. In particular, delivery of peptides, proteins, and miRNAs to the lung is an ongoing challenge. Hence, it is an attractive strategy to test potential targets by employing nanotechnology. Here some of the novel nanomedicine approaches that have been proposed and studied in recent years to facilitate the delivery of therapeutic agents in the setting of critical illnesses such as acute respiratory distress syndrome, sepsis and ventilator associated pneumonia are reviewed. Published by Elsevier B.V.

  7. The role of anxiety in binge eating behavior: a critical examination of theory and empirical literature

    Directory of Open Access Journals (Sweden)

    Diane L. Rosenbaum

    2013-06-01

    Full Text Available The purpose of this manuscript is to expand the understanding of binge eating by reviewing the role of aspects of negative affect. Specifically, this paper will present evidence for further investigation of the bearing that anxiety may have in binge eating development and maintenance. A comprehensive review of the literature regarding the relation of binge eating and anxiety was performed. Valuable contributions have been made to the binge eating literature regarding some aspects of negative affect (i.e., depression; however, outside of bulimia nervosa studies, much of the theoretical and empirical binge eating research to date has not directly addressed the role of anxiety. Research supports expansion of investigations of negative emotionality and binge eating to include specific study of anxiety. Greater inclusivity and specificity in the unique contributions of various negative emotions may further the development of temporal models and intervention efforts.

  8. Critical Conversations and the Role of Dialogue in Delivering Meaningful Improvements in Safety and Security Culture

    International Nuclear Information System (INIS)

    Brissette, S.

    2016-01-01

    Significant scholarship has been devoted to research into safety culture assessment methodologies. These focus on the development, delivery and interpretations of safety culture surveys and other assessment techniques to assure reliable outcomes that provide insights into the safety culture of an organization across multiple dimensions. The lessons from this scholarship can be applied to the emerging area of security culture assessments as the nuclear industry broadens its focus on this topic. The aim of this paper is to discuss the value of establishing mechanisms, immediately after an assessment and regularly between assessments, to facilitate a structured dialogue among leaders around insights derived from an assessment, to enable ongoing improvements in safety and security culture. The leader’s role includes both understanding the current state of culture, the “what is”, and creating regular, open and informed dialogue around their role in shaping the culture to achieve “what should be”.

  9. What Controls Thermo-osmosis? Molecular Simulations Show the Critical Role of Interfacial Hydrodynamics

    Science.gov (United States)

    Fu, Li; Merabia, Samy; Joly, Laurent

    2017-11-01

    Thermo-osmotic and related thermophoretic phenomena can be found in many situations from biology to colloid science, but the underlying molecular mechanisms remain largely unexplored. Using molecular dynamics simulations, we measure the thermo-osmosis coefficient by both mechanocaloric and thermo-osmotic routes, for different solid-liquid interfacial energies. The simulations reveal, in particular, the crucial role of nanoscale interfacial hydrodynamics. For nonwetting surfaces, thermo-osmotic transport is largely amplified by hydrodynamic slip at the interface. For wetting surfaces, the position of the hydrodynamic shear plane plays a key role in determining the amplitude and sign of the thermo-osmosis coefficient. Finally, we measure a giant thermo-osmotic response of the water-graphene interface, which we relate to the very low interfacial friction displayed by this system. These results open new perspectives for the design of efficient functional interfaces for, e.g., waste-heat harvesting.

  10. What Controls Thermo-osmosis? Molecular Simulations Show the Critical Role of Interfacial Hydrodynamics.

    Science.gov (United States)

    Fu, Li; Merabia, Samy; Joly, Laurent

    2017-11-24

    Thermo-osmotic and related thermophoretic phenomena can be found in many situations from biology to colloid science, but the underlying molecular mechanisms remain largely unexplored. Using molecular dynamics simulations, we measure the thermo-osmosis coefficient by both mechanocaloric and thermo-osmotic routes, for different solid-liquid interfacial energies. The simulations reveal, in particular, the crucial role of nanoscale interfacial hydrodynamics. For nonwetting surfaces, thermo-osmotic transport is largely amplified by hydrodynamic slip at the interface. For wetting surfaces, the position of the hydrodynamic shear plane plays a key role in determining the amplitude and sign of the thermo-osmosis coefficient. Finally, we measure a giant thermo-osmotic response of the water-graphene interface, which we relate to the very low interfacial friction displayed by this system. These results open new perspectives for the design of efficient functional interfaces for, e.g., waste-heat harvesting.

  11. Boosting Autonomous Foreign Language Learning: Scrutinizing the Role of Creativity, Critical Thinking, and Vocabulary Learning Strategies

    Directory of Open Access Journals (Sweden)

    Mania Nosratinia

    2015-07-01

    Full Text Available This study set out to investigate the association among English language learners' Autonomy (AU, Creativity (CR, Critical Thinking (CT, and Vocabulary Learning Strategies (VLS. The participants of this study were 202 randomly selected male and female undergraduate (English as a Foreign Language EFL learners, between the ages of 19 and 26 (Mage = 22 years. These participants filled out four questionnaires estimating their AU, CR, CT, and VLS. The characteristics of the collected data legitimated running Pearson's product-moment correlation coefficient. The results suggested that there is a significant and positive relationship between EFL learners' AU and CR, AU and CT, AU and VLS, CR and CT, CR and VLS, as well as their CT and VLS. Considering AU as the predicted variable for this study, it was confirmed that CT is the best predictor of AU. The article concludes with some pedagogical implications and some avenues for future research.

  12. Critical appraisal of the role of everolimus in advanced neuroendocrine tumors of pancreatic origin

    Directory of Open Access Journals (Sweden)

    Mulet-Margalef N

    2012-09-01

    Full Text Available Núria Mulet-Margalef, Jaume CapdevilaMedical Oncology Department, Vall d'Hebron University Hospital, Barcelona, SpainAbstract: For many years, the treatment of advanced pancreatic neuroendocrine tumors (pNETs has been limited almost entirely to somatostatin analogs and streptozocin-based chemotherapy, with modest benefit. Increasing knowledge of the biologic features of pNETs has allowed the design of molecular-based clinical trials, which have taken a step forward in the management of these tumors. In this review, we discuss the molecular rationale for the development of everolimus for patients with advanced pNETs, critically review the clinical data obtained by the main studies in this setting, and discuss essential considerations based on recent findings in pNET biology for future drug development involving the phosphatidylinositol 3' kinase-AKT-mTOR pathway.Keywords: pancreatic neuroendocrine tumors, everolimus, targeted therapies

  13. Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit.

    Science.gov (United States)

    Cevher, Murat A; Shi, Yi; Li, Dan; Chait, Brian T; Malik, Sohail; Roeder, Robert G

    2014-12-01

    The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.

  14. The role of shared neural activations, mirror neurons, and morality in empathy--a critical comment.

    Science.gov (United States)

    Lamm, Claus; Majdandžić, Jasminka

    2015-01-01

    In the last decade, the phenomenon of empathy has received widespread attention by the field of social neuroscience. This has provided fresh insights for theoretical models of empathy, and substantially influenced the academic and public conceptions about this complex social skill. The present paper highlights three key issues which are often linked to empathy, but which at the same time might obscure our understanding of it. These issues are: (1) shared neural activations and whether these can be interpreted as evidence for simulation accounts of empathy; (2) the causal link of empathy to our presumed mirror neuron system; and (3) the question whether increasing empathy will result in better moral decisions and behaviors. The aim of our review is to provide the basis for critically evaluating our current understanding of empathy, and its public reception, and to inspire new research directions. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. How to Identify Negative Attitudes towards Inclusive Education: Critical Discourse Analysis of Russian Transcripts Using Role and Reference Grammar

    Directory of Open Access Journals (Sweden)

    Mariia Rubtcova

    2016-09-01

    Full Text Available This paper presents the Role and Reference Grammar (RRG analysis that aims to reveal possibilities required for carrying out the interdisciplinary research development within Critical Discourse Analysis (CDA. It takes a closer look at conflicts, considering the example of a conflict situation occurred in reaction to the opening of the inclusive academic programme at one of St. Petersburg’s secondary schools. Role and Reference Grammar application demonstrates that the use of different verb types and macroroles has led to the various interpretations. These findings confirm that RRG could influence the increase of objectivity of the transcript analysis in qualitative social research. RRG provides new information which in combination with other methods can help us to understand the positions of participants involved into conflicts

  16. Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury.

    Science.gov (United States)

    Calì, Bianca; Ceolin, Stefano; Ceriani, Federico; Bortolozzi, Mario; Agnellini, Andrielly H R; Zorzi, Veronica; Predonzani, Andrea; Bronte, Vincenzo; Molon, Barbara; Mammano, Fabio

    2015-04-30

    Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding "bystander" cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely defined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxide (NO) that diffuses to bystander cells, in which NO levels are further increased by a mechanism compatible with Ca(2+)-dependent enzymatic production. We detected similar signals in tumors grown in dorsal skinfold chambers applied to live mice. Pharmacological blockade of connexin channels significantly reduced the extent of apoptosis in bystander cells, consistent with a critical role played by intercellular communication, Ca2+ and NO in the bystander effects triggered by photodynamic therapy.

  17. The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease.

    Science.gov (United States)

    van der Veen, Jelske N; Kennelly, John P; Wan, Sereana; Vance, Jean E; Vance, Dennis E; Jacobs, René L

    2017-09-01

    Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the most abundant phospholipids in all mammalian cell membranes. In the 1950s, Eugene Kennedy and co-workers performed groundbreaking research that established the general outline of many of the pathways of phospholipid biosynthesis. In recent years, the importance of phospholipid metabolism in regulating lipid, lipoprotein and whole-body energy metabolism has been demonstrated in numerous dietary studies and knockout animal models. The purpose of this review is to highlight the unappreciated impact of phospholipid metabolism on health and disease. Abnormally high, and abnormally low, cellular PC/PE molar ratios in various tissues can influence energy metabolism and have been linked to disease progression. For example, inhibition of hepatic PC synthesis impairs very low density lipoprotein secretion and changes in hepatic phospholipid composition have been linked to fatty liver disease and impaired liver regeneration after surgery. The relative abundance of PC and PE regulates the size and dynamics of lipid droplets. In mitochondria, changes in the PC/PE molar ratio affect energy production. We highlight data showing that changes in the PC and/or PE content of various tissues are implicated in metabolic disorders such as atherosclerosis, insulin resistance and obesity. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Theoretical Availability versus Practical Accessibility: The Critical Role of Metadata Management in Open Data Portals

    Directory of Open Access Journals (Sweden)

    Thomas Schauppenlehner

    2018-02-01

    Full Text Available As a consequence of policies such as the EU Public Sector Initiative, authorities across Europe have been moving towards providing free access to a wide range of statistical data and in particular geodata. From the diverse end-users’ perspective (general public, interest groups, students, other authorities, etc., access to data requires specific knowledge, methods, and guidance in identifying and using the relevant content. Metadata are a key concept for the description and classification of data and thus also for ensuring their long-term value. We analyze the European Data Portal as well as one national metadatabase (Austrian Data Portal with regard to aspects such as data search functionality, keyword consistency, spatial referencing, data format and data license information. In both cases, we found extensive inconsistencies and conceptual weaknesses that heavily limit the practical accessibility. The mere presence of metadata is no indicator for the usability of the data. We argue for a better definition and structuring of the interface between the numerous data providers and the metadatabases.

  19. On the role of cavitation in particle collection in flotation - A critical review. II

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Z.A.; Xu, Z.H.; Finch, J.A.; Masliyah, J.H.; Chow, R.S. [Alberta Research Council, Edmonton, AB (Canada)

    2009-04-15

    Research in applying hydrodynamic cavitation to recovery of natural resources during the last decade is reviewed. The existence and formation of tiny bubbles or gas nuclei (diameter from microns down to nano sizes) in natural water were verified from both direct and in-direct measurements, providing a foundation for applying hydrodynamic cavitation to flotation systems. The interactions between tiny bubbles and fine particles in aqueous slurry were analysed. Tiny bubbles generated by hydrodynamic cavitation increased contact angle of solids and hence attachment force, bridge fine particles to form aggregates, minimize slime coating, remove oxidation layers on particle surfaces, and in hence reduce reagents consumption. Experiments revealed that the energy dissipation levels for cavity formation in a flowing liquid could be much lower than predicted, depending on the content of dissolved gases, presence of free gas nuclei and design of cavitation tubes. Application of hydrodynamic cavitation to fine and coarse particle flotation, high intensity conditioning, oil agglomeration of fine coal, and oil sands processing has confirmed the role of tiny bubbles formed by cavitation in improving recovery efficiency. Increased flotation kinetics by hydrodynamic cavitation could be attributed to a dual role: some collapsing cavity bubbles serving to break interfacial layers on particle surfaces while other cavity bubbles attaching to those freshly exposed mineral surfaces. The role of water vapor and other gases within cavity bubbles in particle-bubble attachment remains to be explored. Incorporating hydrodynamic cavitation into flotation systems to take advantage of its unique features is expected to develop the next generation of flotation machines.

  20. A critical role for topoisomerase IIb and DNA double strand breaks in transcription.

    Science.gov (United States)

    Calderwood, Stuart K

    2016-05-26

    Recent studies have indicated a novel role for topoisomerase IIb in transcription. Transcription of heat shock genes, serum-induced immediate early genes and nuclear receptor-activated genes, each required DNA double strands generated by topoisomerase IIb. Such strand breaks seemed both necessary and sufficient for transcriptional activation. In addition, such transcription was associated with initiation of the DNA damage response pathways, including the activation of the enzymes: ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase and poly (ADP ribose) polymerase 1. DNA damage response signaling was involved both in transcription and in repair of DNA breaks generated by topoisomerase IIb.

  1. Critical appraisal of the role of ruxolitinib in myeloproliferative neoplasm-associated myelofibrosis

    Directory of Open Access Journals (Sweden)

    Barosi G

    2015-05-01

    Full Text Available Giovanni Barosi,1 Vittorio Rosti,1 Robert Peter Gale2 1Center for the Study of Myelofibrosis, IRCCS Policlinico S Matteo Foundation, Pavia, Italy; 2Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK Abstract: The recent approval of molecular-targeted therapies for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF has dramatically changed its therapeutic landscape. Ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor, is now widely used for first- and second-line therapy in persons with MPN-MF, especially those with disease-related splenomegaly, intermediate- or high-risk disease, and constitutional symptoms. The goal of this work is to critically analyze data supporting use of ruxolitinib in the clinical settings approved by the US Food and Drug Administration (FDA and European Medicines Agency (EMA. We systematically reviewed the literature and analyzed the risk of biases in the two randomized studies (COMFORT I and COMFORT II on which FDA and EMA approval was based. Our strategy was to apply the Grading of Recommendation, Assessment, Development and Evaluation (GRADE approach by evaluating five dimensions of evidence: (1 overall risk of bias, (2 imprecision, (3 inconsistency, (4 indirectness, and (5 publication bias. Based on these criteria, we downgraded the evidence from the COMFORT I and COMFORT II trials for performance, attrition, and publication bias. In the disease-associated splenomegaly sphere, we upgraded the quality of evidence because of large effect size but downgraded it because of comparator choice and outcome indirectness (quality of evidence, low. In the sphere of treating persons with intermediate- or high-risk disease, we downgraded the evidence because of imprecision in effect size measurement and population indirectness. In the sphere of disease-associated symptoms, we upgraded the evidence because of the large effect size, but downgraded it

  2. Knowing, Applying, and Reasoning about Arithmetic: Roles of Domain-General and Numerical Skills in Multiple Domains of Arithmetic Learning

    Science.gov (United States)

    Zhang, Xiao; Räsänen, Pekka; Koponen, Tuire; Aunola, Kaisa; Lerkkanen, Marja-Kristiina; Nurmi, Jari-Erik

    2017-01-01

    The longitudinal relations of domain-general and numerical skills at ages 6-7 years to 3 cognitive domains of arithmetic learning, namely knowing (written computation), applying (arithmetic word problems), and reasoning (arithmetic reasoning) at age 11, were examined for a representative sample of 378 Finnish children. The results showed that…

  3. Autophagy plays a critical role in ChLym-1-induced cytotoxicity of non-hodgkin's lymphoma cells.

    Directory of Open Access Journals (Sweden)

    Jiajun Fan

    Full Text Available Autophagy is a critical mechanism in both cancer therapy resistance and tumor suppression. Monoclonal antibodies have been documented to kill tumor cells via apoptosis, antibody-dependent cellular cytotoxicity (ADCC and complement-dependent cytotoxicity (CDC. In this study, we report for the first time that chLym-1, a chimeric anti-human HLA-DR monoclonal antibody, induces autophagy in Raji Non-Hodgkin's Lymphoma (NHL cells. Interestingly, inhibition of autophagy by pharmacological inhibitors (3-methyladenine and NH4Cl or genetic approaches (siRNA targeting Atg5 suppresses chLym-1-induced growth inhibition, apoptosis, ADCC and CDC in Raji cells, while induction of autophagy could accelerate cytotoxic effects of chLym-1 on Raji cells. Furthermore, chLym-1-induced autophagy can mediate apoptosis through Caspase 9 activation, demonstrating the tumor-suppressing role of autophagy in antilymphoma effects of chLym-1. Moreover, chLym-1 can activate several upstream signaling pathways of autophagy including Akt/mTOR and extracellular signal-regulated kinase 1/2 (Erk1/2. These results elucidate the critical role of autophagy in cytotoxicity of chLym-1 antibody and suggest a potential therapeutic strategy of NHL therapy by monoclonal antibody chLym-1 in combination with autophagy inducer.

  4. The critical role of Golgi cells in regulating spatio-temporal integration and plasticity at the cerebellum input stage

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available After the discovery at the end of the 19th century (Golgi, 1883, the Golgi cell was precisely described by S.R. y Cajal (see Cajal, 1987, 1995 and functionally identified as an inhibitory interneuron 50 years later by J.C. Eccles and colleagues (Eccles e al., 1967. Then, its role has been casted by Marr (1969 within the Motor Learning Theory as a codon size regulator of granule cell activity. It was immediately clear that Golgi cells had to play a critical role, since they are the main inhibitory interneuron of the granular layer and control activity of as many as 100 millions granule cells. In vitro, Golgi cells show pacemaking, resonance, phase-reset and rebound-excitation in the theta-frequency band. These properties are likely to impact on their activity in vivo, which shows irregular spontaneous beating modulated by sensory inputs and burst responses to punctuate stimulation followed by a silent pause. Moreover, investigations have given insight into Golgi cells connectivity within the cerebellar network and on their impact on the spatio-temporal organization of activity. It turns out that Golgi cells can control both the temporal dynamics and the spatial distribution of information transmitted through the cerebellar network. Moreover, Golgi cells regulate the induction of long-term synaptic plasticity at the mossy fiber - granule cell synapse. Thus, the concept is emerging that Golgi cells are of critical importance for regulating granular layer network activity bearing important consequences for cerebellar computation as a whole.

  5. Present knowledge and perspectives on the role of copper in brake materials and related environmental issues: A critical assessment

    International Nuclear Information System (INIS)

    Straffelini, Giovanni; Ciudin, Rodica; Ciotti, Alessandro; Gialanella, Stefano

    2015-01-01

    This critical review presents several aspects related to the use of copper as a main component in brake pads in road vehicles. The compositions of these materials are attracting increasing interest and concern due to the relative contribution of wear products to particulate matter emissions in the environment as a result of braking action even though there has been a reduction in exhaust products from internal combustion engines. We review the data on the main wear mechanisms in brake systems and highlight the positive role of copper. However, similar to other heavy metal emissions, even the release of copper into the atmosphere may have important environmental and health effects. Thus, several replacement strategies are being pursued, and the positive and negative features will be critically reviewed. Additionally, the future perspectives in materials development will be discussed. - Highlights: • Copper in brake pad materials: role and concerns. • Environmental and health impact of copper. • Copper replacement in frictional brake materials. • International legislation and standards on the above issues. - Importance of copper in brake pad materials and concern as regards environmental and health impact of its emission as brake wear product.

  6. Red blood cells in hemorrhagic shock: a critical role for glutaminolysis in fueling alanine transamination in rats.

    Science.gov (United States)

    Reisz, Julie A; Slaughter, Anne L; Culp-Hill, Rachel; Moore, Ernest E; Silliman, Christopher C; Fragoso, Miguel; Peltz, Erik D; Hansen, Kirk C; Banerjee, Anirban; D'Alessandro, Angelo

    2017-07-25

    Red blood cells (RBCs) are the most abundant host cell in the human body and play a critical role in oxygen transport and systemic metabolic homeostasis. Hypoxic metabolic reprogramming of RBCs in response to high-altitude hypoxia or anaerobic storage in the blood bank has been extensively described. However, little is known about the RBC metabolism following hemorrhagic shock (HS), the most common preventable cause of death in trauma, the global leading cause of total life-years lost. Metabolomics analyses were performed through ultra-high pressure liquid chromatography-mass spectrometry on RBCs from Sprague-Dawley rats undergoing HS (mean arterial pressure [MAP], 80 mm Hg). Steady-state measurements were accompanied by metabolic flux analysis upon tracing of in vivo-injected 13 C 15 N-glutamine or inhibition of glutaminolysis using the anticancer drug CB-839. RBC metabolic phenotypes recapitulated the systemic metabolic reprogramming observed in plasma from the same rodent model. Results indicate that shock RBCs rely on glutamine to fuel glutathione (GSH) synthesis and pyruvate transamination, whereas abrogation of glutaminolysis conferred early mortality and exacerbated lactic acidosis and systemic accumulation of succinate, a predictor of mortality in the military and civilian critically ill populations. Glutamine is here identified as an essential amine group donor in HS RBCs, plasma, liver, and lungs, providing additional rationale for the central role glutaminolysis plays in metabolic reprogramming and survival following severe hemorrhage.

  7. Revisiting Primary Care's Critical Role in Achieving Health Equity: Pisacano Scholars' Reflections from Starfield Summit II.

    Science.gov (United States)

    Park, Brian; Coutinho, Anastasia J; Doohan, Noemi; Jimenez, Jonathan; Martin, Sara; Romano, Max; Wohler, Diana; DeVoe, Jennifer

    2018-01-01

    The second Starfield Summit was held in Portland, Oregon, in April 2017. The Summit addressed the role of primary care in advancing health equity by focusing on 4 key domains: social determinants of health in primary care, vulnerable populations, economics and policy, and social accountability. Invited participants represented an interdisciplinary group of primary care clinicians, researchers, educators, policymakers, community leaders, and trainees. The Pisacano Leadership Foundation was one of the Summit sponsors and held its annual leadership symposium in conjunction with the Summit, enabling several Pisacano Scholars to attend the Summit. After the Summit, a small group of current and former Pisacano Scholars formed a writing group to highlight key themes and implications for action discussed at the Summit. The Summit resonated as a call to action for primary care to move beyond identifying existing health inequities and toward the development of interventions that advance health equity, through education, research, and enhanced community partnerships. In doing so, the Summit aimed to build on the foundational work of Dr. Starfield, challenging us to explore the significant role of primary care in truly achieving health equity. © Copyright 2018 by the American Board of Family Medicine.

  8. A critical appraisal of the role of neuropsychological deficits in preschool ADHD.

    Science.gov (United States)

    Sjöwall, Douglas; Thorell, Lisa B

    2018-03-14

    The present study aimed at improving our understanding of the role of neuropsychological deficits in preschool Attention Deficit Hyperactivity Disorder (ADHD). The study included 52 children in the ADHD group and 72 controls (age 4-6 years). Both laboratory measures and teacher reports of executive deficits (i.e., working memory, inhibition, and shifting), delay-related behaviors (i.e., the preference for minimizing delay), and emotional functions (i.e., emotion recognition and regulation) were included. Variable-oriented analyses were complemented with person-oriented analyses (i.e., identifying the proportion of patients considered impaired). Results showed that the ADHD group differed from controls with regard to all measures of executive functioning and most measures of delay-related behaviors, but few differences were found for emotional functioning. A substantial subgroup (23%) of children with ADHD did not have a neuropsychological deficit in any domain. There were subgroups with executive or delay-related deficits only, but no pure emotional subgroup. The overlap between different neuropsychological deficits was much larger when teacher reports were used as opposed to laboratory measures. Regarding functional impairments, large mean differences were found between the ADHD group and controls. However, neuropsychological deficits were not able to explain individual variations in daily life functioning among children with ADHD. In conclusion, the present study identified some important methodological and theoretical issues regarding the role of neuropsychological functioning in preschool ADHD.

  9. Homologous Recombination DNA Repair Genes Play a Critical Role in Reprogramming to a Pluripotent State

    Directory of Open Access Journals (Sweden)

    Federico González

    2013-03-01

    Full Text Available Induced pluripotent stem cells (iPSCs hold great promise for personalized regenerative medicine. However, recent studies show that iPSC lines carry genetic abnormalities, suggesting that reprogramming may be mutagenic. Here, we show that the ectopic expression of reprogramming factors increases the level of phosphorylated histone H2AX, one of the earliest cellular responses to DNA double-strand breaks (DSBs. Additional mechanistic studies uncover a direct role of the homologous recombination (HR pathway, a pathway essential for error-free repair of DNA DSBs, in reprogramming. This role is independent of the use of integrative or nonintegrative methods in introducing reprogramming factors, despite the latter being considered a safer approach that circumvents genetic modifications. Finally, deletion of the tumor suppressor p53 rescues the reprogramming phenotype in HR-deficient cells primarily through the restoration of reprogramming-dependent defects in cell proliferation and apoptosis. These mechanistic insights have important implications for the design of safer approaches to creating iPSCs.

  10. The role of body image in prenatal and postpartum depression: a critical review of the literature.

    Science.gov (United States)

    Silveira, Marushka L; Ertel, Karen A; Dole, Nancy; Chasan-Taber, Lisa

    2015-06-01

    Maternal depression increases risk of adverse perinatal outcomes, and recent evidence suggests that body image may play an important role in depression. This systematic review identifies studies of body image and perinatal depression with the goal of elucidating the complex role that body image plays in prenatal and postpartum depression, improving measurement, and informing next steps in research. We conducted a literature search of the PubMed database (1996-2014) for English language studies of (1) depression, (2) body image, and (3) pregnancy or postpartum. In total, 19 studies matched these criteria. Cross-sectional studies consistently found a positive association between body image dissatisfaction and perinatal depression. Prospective cohort studies found that body image dissatisfaction predicted incident prenatal and postpartum depression; findings were consistent across different aspects of body image and various pregnancy and postpartum time periods. Prospective studies that examined the reverse association found that depression influenced the onset of some aspects of body image dissatisfaction during pregnancy, but few evaluated the postpartum onset of body image dissatisfaction. The majority of studies found that body image dissatisfaction is consistently but weakly associated with the onset of prenatal and postpartum depression. Findings were less consistent for the association between perinatal depression and subsequent body image dissatisfaction. While published studies provide a foundation for understanding these issues, methodologically rigorous studies that capture the perinatal variation in depression and body image via instruments validated in pregnant women, consistently adjust for important confounders, and include ethnically diverse populations will further elucidate this association.

  11. Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures

    Science.gov (United States)

    Li, Min; Ma, Tao; Wu, Shengdun; Ma, Jingling; Cui, Yan; Xia, Yang; Xu, Peng; Yao, Dezhong

    2015-01-01

    The basal ganglia (BG), serving as an intermediate bridge between the cerebral cortex and thalamus, are believed to play crucial roles in controlling absence seizure activities generated by the pathological corticothalamic system. Inspired by recent experiments, here we systematically investigate the contribution of a novel identified GABAergic pallido-cortical pathway, projecting from the globus pallidus externa (GPe) in the BG to the cerebral cortex, to the control of absence seizures. By computational modelling, we find that both increasing the activation of GPe neurons and enhancing the coupling strength of the inhibitory pallido-cortical pathway can suppress the bilaterally synchronous 2–4 Hz spike and wave discharges (SWDs) during absence seizures. Appropriate tuning of several GPe-related pathways may also trigger the SWD suppression, through modulating the activation level of GPe neurons. Furthermore, we show that the previously discovered bidirectional control of absence seizures due to the competition between other two BG output pathways also exists in our established model. Importantly, such bidirectional control is shaped by the coupling strength of this direct GABAergic pallido-cortical pathway. Our work suggests that the novel identified pallido-cortical pathway has a functional role in controlling absence seizures and the presented results might provide testable hypotheses for future experimental studies. PMID:26496656

  12. Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.

    Science.gov (United States)

    Zhang, Qia; Joshi, Sunil K; Lovett, David H; Zhang, Bryon; Bodine, Sue; Kim, Hubert T; Liu, Xuhui

    2014-01-01

    extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

  13. Fungi contribute critical but spatially varying roles in nitrogen and carbon cycling in acid mine drainage

    Directory of Open Access Journals (Sweden)

    Annika C. Mosier

    2016-03-01

    Full Text Available The ecosystem roles of fungi have been extensively studied by targeting one organism and/or biological process at a time, but the full metabolic potential of fungi has rarely been captured in an environmental context. We hypothesized that fungal genome sequences could be assembled directly from the environment using metagenomics and that transcriptomics and proteomics could simultaneously reveal metabolic differentiation across habitats. We reconstructed the near-complete 27 Mbp genome of a filamentous fungus, Acidomyces richmondensis, and evaluated transcript and protein expression in floating and streamer biofilms from an acid mine drainage system. A. richmondensis transcripts involved in denitrification and in the degradation of complex carbon sources (including cellulose were up-regulated in floating biofilms, whereas central carbon metabolism and stress-related transcripts were significantly up-regulated in streamer biofilms. These findings suggest that the biofilm niches are distinguished by distinct carbon and nitrogen resource utilization, oxygen availability and environmental challenges. An isolated A. richmondensis strain from this environment was used to validate the metagenomics-derived genome and confirm nitrous oxide production at pH 1. Overall, our analyses defined mechanisms of fungal adaptation and identified a functional shift related to different roles in carbon and nitrogen turnover for the same species of fungi growing in closely located but distinct biofilm niches.

  14. Allergen recognition by innate immune cells: critical role of dendritic and epithelial cells

    Directory of Open Access Journals (Sweden)

    Fabian eSalazar

    2013-11-01

    Full Text Available Allergy is an exacerbated response of the immune system against non-self-proteins called allergens and is typically characterized by biased type-2 T helper cell and deleterious IgE mediated immune responses. The allergic cascade starts with the recognition of allergens by antigen presenting cells, mainly dendritic cells, culminating in mast cell sensitization and triggering. Dendritic cells have been demonstrated to play a crucial role in orchestrating allergic diseases. Using different C-type lectin receptors dendritic cells are able to recognize and internalize a number of allergens from diverse sources leading to sensitization. Furthermore, there is increasing evidence highlighting the role of epithelial cells in triggering and modulating immune responses to allergens. As well as providing a physical barrier, epithelial cells can interact with allergens and influence dendritic cells behaviour through the release of a number of Th2 promoting cytokines. In this review we will summarise current understanding of how allergens are recognised by dendritic cells and epithelial cells and what are the consequences of such interaction in the context of allergic sensitisation and downstream events leading to allergic inflammation. Better understanding of the molecular mechanisms of allergen recognition and associated signalling pathways could enable developing more effective therapeutic strategies that target the initial steps of allergic sensitisation hence hindering development or progression of allergic diseases.

  15. Target of rapamycin (TOR) plays a critical role in triacylglycerol accumulation in microalgae.

    Science.gov (United States)

    Imamura, Sousuke; Kawase, Yasuko; Kobayashi, Ikki; Sone, Toshiyuki; Era, Atsuko; Miyagishima, Shin-Ya; Shimojima, Mie; Ohta, Hiroyuki; Tanaka, Kan

    2015-10-01

    Most microalgae produce triacylglycerol (TAG) under stress conditions such as nitrogen depletion, but the underlying molecular mechanism remains unclear. In this study, we focused on the role of target of rapamycin (TOR) in TAG accumulation. TOR is a serine/threonine protein kinase that is highly conserved and plays pivotal roles in nitrogen and other signaling pathways in eukaryotes. We previously constructed a rapamycin-susceptible Cyanidioschyzon merolae, a unicellular red alga, by expressing yeast FKBP12 protein to evaluate the results of TOR inhibition (Imamura et al. in Biochem Biophys Res Commun 439:264-269, 2013). By using this strain, we here report that rapamycin-induced TOR inhibition results in accumulation of cytoplasmic lipid droplets containing TAG. Transcripts for TAG synthesis-related genes, such as glycerol-3-phosphate acyltransferase and acyl-CoA:diacylglycerol acyltransferase (DGAT), were increased by rapamycin treatment. We also found that fatty acid synthase-dependent de novo fatty acid synthesis was required for the accumulation of lipid droplets. Induction of TAG and up-regulation of DGAT gene expression by rapamycin were similarly observed in the unicellular green alga, Chlamydomonas reinhardtii. These results suggest the general involvement of TOR signaling in TAG accumulation in divergent microalgae.

  16. Emerging critical roles of Fe-S clusters in DNA replication and repair

    Science.gov (United States)

    Fuss, Jill O.; Tsai, Chi-Lin; Ishida, Justin P.; Tainer, John A.

    2015-01-01

    Fe-S clusters are partners in the origin of life that predate cells, acetyl-CoA metabolism, DNA, and the RNA world. The double helix solved the mystery of DNA replication by base pairing for accurate copying. Yet, for genome stability necessary to life, the double helix has equally important implications for damage repair. Here we examine striking advances that uncover Fe-S cluster roles both in copying the genetic sequence by DNA polymerases and in crucial repair processes for genome maintenance, as mutational defects cause cancer and degenerative disease. Moreover, we examine an exciting, controversial role for Fe-S clusters in a third element required for life – the long-range coordination and regulation of replication and repair events. By their ability to delocalize electrons over both Fe and S centers, Fe-S clusters have unbeatable features for protein conformational control and charge transfer via double-stranded DNA that may fundamentally transform our understanding of life, replication, and repair. PMID:25655665

  17. The critical roles of information and nonequilibrium thermodynamics in evolution of living systems.

    Science.gov (United States)

    Gatenby, Robert A; Frieden, B Roy

    2013-04-01

    Living cells are spatially bounded, low entropy systems that, although far from thermodynamic equilibrium, have persisted for billions of years. Schrödinger, Prigogine, and others explored the physical principles of living systems primarily in terms of the thermodynamics of order, energy, and entropy. This provided valuable insights, but not a comprehensive model. We propose the first principles of living systems must include: (1) Information dynamics, which permits conversion of energy to order through synthesis of specific and reproducible, structurally-ordered components; and (2) Nonequilibrium thermodynamics, which generate Darwinian forces that optimize the system.Living systems are fundamentally unstable because they exist far from thermodynamic equilibrium, but this apparently precarious state allows critical response that includes: (1) Feedback so that loss of order due to environmental perturbations generate information that initiates a corresponding response to restore baseline state. (2) Death due to a return to thermodynamic equilibrium to rapidly eliminate systems that cannot maintain order in local conditions. (3) Mitosis that rewards very successful systems, even when they attain order that is too high to be sustainable by environmental energy, by dividing so that each daughter cell has a much smaller energy requirement. Thus, nonequilibrium thermodynamics are ultimately responsible for Darwinian forces that optimize system dynamics, conferring robustness sufficient to allow continuous existence of living systems over billions of years.

  18. Brief Mindfulness Meditation Training Reduces Mind-Wandering: The Critical Role of Acceptance

    Science.gov (United States)

    Rahl, Hayley A.; Lindsay, Emily K.; Pacilio, Laura E.; Brown, Kirk W.; Creswell, J. David

    2016-01-01

    Mindfulness meditation programs, which train individuals to monitor their present moment experience in an open or accepting way, have been shown to reduce mind-wandering on standardized tasks in several studies. Here we test two competing accounts for how mindfulness training reduces mind-wandering, evaluating whether the attention monitoring component of mindfulness training alone reduces mind-wandering or whether the acceptance training component is necessary for reducing mind-wandering. Healthy young adults (N=147) were randomized to either a 3-day brief mindfulness training condition incorporating instruction in both attention monitoring and acceptance, a mindfulness training condition incorporating attention monitoring instruction only, a relaxation training condition, or a reading control condition. Participants completed measures of dispositional mindfulness and treatment expectancies before the training session on Day 1 and then completed a 6-minute Sustained Attention Response Task (SART) measuring mind-wandering after the training session on Day 3. Acceptance training was important for reducing mind-wandering, such that the monitoring + acceptance mindfulness training condition had the lowest mind-wandering relative to the other conditions, including significantly lower mind-wandering relative to the monitor-only mindfulness training condition. In one of the first experimental mindfulness training dismantling studies to-date, we show that training in acceptance is a critical driver of mindfulness training reductions in mind-wandering. This effect suggests that acceptance skills may facilitate emotion regulation on boring and frustrating sustained attention tasks that foster mind-wandering, such as the SART. PMID:27819445

  19. The critical role of psychosomatics in promoting a new perspective upon health and disease.

    Science.gov (United States)

    Dragoş, Dorin; Tănăsescu, Maria Daniela

    2009-01-01

    In an evolutionary model, health and disease are regarded as successful and respectively failed adaptation to the demands of the environment. The social factors are critical for a successful adaptation, while emotions are means of both signaling the organism's state and of adapting the physiological responses to environmental challenges. Hence the importance of a biopsychosocial model of health and disease. Psychoemotional distress generates and/or amplifies somatic symptoms. Somatization may be viewed as an altered cognitive process, inclining the individual to an augmented perception of bodily sensations and to an increased degree of complexity in reporting negative experiences (hence the greater cognitive effort allocated thereto). Somatosensory amplification and alexithymia are key elements in this process. The brain's right hemisphere is more involved in the generation of emotionally conditioned somatization symptoms. Somatic symptoms have various psychological and social functions and are strongly influenced by the particular belief system of the individual. Inappropriately perceiving the environment as an aggressor and excessively responding to it (by activating the cytokine system in correlation with the arousal of the psychic, nervous, and endocrine systems) may be a key element in the altered cognition conducive to ill health.

  20. Critical role of heme oxygenase-1 in Foxp3-mediated immune suppression

    International Nuclear Information System (INIS)

    Choi, Byung-Min; Pae, Hyun-Ock; Jeong, Young-Ran; Kim, Young-Myeong; Chung, Hun-Taeg

    2005-01-01

    Foxp3, which encodes the transcription factor scurfin, is indispensable for the development and function of CD4 + CD25 + regulatory T cells (Treg). Recent data suggest conversion of peripheral CD4 + CD25 - naive T cells to CD4 + CD25 + Treg by acquisition of Foxp3 through costimulation with TCR and TGF-β or forced expression of the gene. One critical question is how Foxp3 causes T cells to become regulatory. In the present work, we demonstrate that Foxp3 can induce heme oxygenase-1 (HO-1) expression and subsequently such regulatory phenotypes as the suppression of nontransfected cells in a cell-cell contact-dependent manner as well as impaired proliferation and production of cytokines upon stimulation in Jurkat T cells. Moreover, we confirm the expression of both Foxp3 and HO-1 in peripheral CD4 + CD25 + Treg and suppressive function of the cells are relieved by the inhibition of HO-1 activity. In summary, we demonstrate that Foxp3 induces HO-1 expression and HO-1 engages in Foxp3-mediated immune suppression

  1. Questioning the Role of Requirements Engineering in the Causes of Safety-Critical Software Failures

    Science.gov (United States)

    Johnson, C. W.; Holloway, C. M.

    2006-01-01

    Many software failures stem from inadequate requirements engineering. This view has been supported both by detailed accident investigations and by a number of empirical studies; however, such investigations can be misleading. It is often difficult to distinguish between failures in requirements engineering and problems elsewhere in the software development lifecycle. Further pitfalls arise from the assumption that inadequate requirements engineering is a cause of all software related accidents for which the system fails to meet its requirements. This paper identifies some of the problems that have arisen from an undue focus on the role of requirements engineering in the causes of major accidents. The intention is to provoke further debate within the emerging field of forensic software engineering.

  2. Information technologies and the sharing of disaster knowledge: the critical role of professional culture.

    Science.gov (United States)

    Marincioni, Fausto

    2007-12-01

    A comparative survey of a diverse sample of 96 US and Italian emergency management agencies shows that the diffusion of new information technologies (IT) has transformed disaster communications. Although these technologies permit access to and the dissemination of massive amounts of disaster information with unprecedented speed and efficiency, barriers rooted in the various professional cultures still hinder the sharing of disaster knowledge. To be effective the available IT must be attuned to the unique settings and professional cultures of the local emergency management communities. Findings show that available technology, context, professional culture and interaction are key factors that affect the knowledge transfer process. Cultural filters appear to influence emergency managers' perceptions of their own professional roles, their vision of the applicability of technology to social issues, and their perspective on the transferability of disaster knowledge. Four cultural approaches to the application of IT to disaster communications are defined: technocentric; geographic,; anthropocentric; and ecocentric.

  3. A critical evaluation of science outreach via social media: its role and impact on scientists.

    Science.gov (United States)

    McClain, Craig; Neeley, Liz

    2014-01-01

    The role of scientists in social media and its impact on their careers are not fully explored.  While policies and best practices are still fluid, it is concerning that discourse is often based on little to no data, and some arguments directly contradict the available data.  Here, we consider the relevant but subjective questions about science outreach via social media (SOSM), specifically: (1) Does a public relations nightmare exist for science?; (2) Why (or why aren't) scientists engaging in social media?; (3) Are scientists using social media well?; and (4) Will social media benefit a scientist's career? We call for the scientific community to create tangible plans that value, measure, and help manage scientists' social media engagement.

  4. Hormones in the immune system and their possible role. A critical review.

    Science.gov (United States)

    Csaba, György

    2014-09-01

    Immune cells synthesize, store and secrete hormones, which are identical with the hormones of the endocrine glands. These are: the POMC hormones (ACTH, endorphin), the thyroid system hormones (TRH, TSH, T3), growth hormone (GH), prolactin, melatonin, histamine, serotonin, catecholamines, GnRH, LHRH, hCG, renin, VIP, ANG II. This means that the immune cells contain all of the hormones, which were searched at all and they also have receptors for these hormones. From this point of view the immune cells are similar to the unicells (Tetrahymena), so it can be supposed that these cells retained the properties characteristic at a low level of phylogeny while other cells during the evolution accumulated to form endocrine glands. In contrast to the glandular endocrine cells, immune cells are polyproducers and polyreceivers. As they are mobile cells, they are able to transport the stored hormone to different places (packed transport) or attracted by local factors, accumulate in the neighborhood of the target, synthesizing and secreting hormones locally. This is taking place, e.g. in the case of endorphin, where the accumulating immune cells calms pain caused by the inflammation. The targeted packed transport is more economical than the hormone-pouring to the blood circulation of glandular endocrines and the targeting also cares the other receptor-bearing cells timely not needed the effect. Mostly the immune-effects of immune-cell derived hormones were studied (except endorphin), however, it is not exactly cleared, while the system could have scarcely studied important roles in other cases. The evolutionary aspects and the known as well, as possible roles of immune-endocrine system and their hormones are listed and discussed.

  5. Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Quan-Guang Zhang

    Full Text Available BACKGROUND: Oxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O(2(-, and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI. METHODOLOGY/PRINCIPAL FINDINGS: The results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24-96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O(2(- induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins β-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI. CONCLUSIONS/SIGNIFICANCE: As a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI.

  6. Mig-6 plays a critical role in the regulation of cholesterol homeostasis and bile acid synthesis.

    Directory of Open Access Journals (Sweden)

    Bon Jeong Ku

    Full Text Available The disruption of cholesterol homeostasis leads to an increase in cholesterol levels which results in the development of cardiovascular disease. Mitogen Inducible Gene 6 (Mig-6 is an immediate early response gene that can be induced by various mitogens, stresses, and hormones. To identify the metabolic role of Mig-6 in the liver, we conditionally ablated Mig-6 in the liver using the Albumin-Cre mouse model (Alb(cre/+Mig-6(f/f; Mig-6(d/d. Mig-6(d/d mice exhibit hepatomegaly and fatty liver. Serum levels of total, LDL, and HDL cholesterol and hepatic lipid were significantly increased in the Mig-6(d/d mice. The daily excretion of fecal bile acids was significantly decreased in the Mig-6(d/d mice. DNA microarray analysis of mRNA isolated from the livers of these mice showed alterations in genes that regulate lipid metabolism, bile acid, and cholesterol synthesis, while the expression of genes that regulate biliary excretion of bile acid and triglyceride synthesis showed no difference in the Mig-6(d/d mice compared to Mig-6(f/f controls. These results indicate that Mig-6 plays an important role in cholesterol homeostasis and bile acid synthesis. Mice with liver specific conditional ablation of Mig-6 develop hepatomegaly and increased intrahepatic lipid and provide a novel model system to investigate the genetic and molecular events involved in the regulation of cholesterol homeostasis and bile acid synthesis. Defining the molecular mechanisms by which Mig-6 regulates cholesterol homeostasis will provide new insights into the development of more effective ways for the treatment and prevention of cardiovascular disease.

  7. A critical role for protein degradation in the nucleus accumbens core in cocaine reward memory.

    Science.gov (United States)

    Ren, Zhen-Yu; Liu, Meng-Meng; Xue, Yan-Xue; Ding, Zeng-Bo; Xue, Li-Fen; Zhai, Suo-Di; Lu, Lin

    2013-04-01

    The intense associative memories that develop between cocaine-paired contexts and rewarding stimuli contribute to cocaine seeking and relapse. Previous studies have shown impairment in cocaine reward memories by manipulating a labile state induced by memory retrieval, but the mechanisms that underlie the destabilization of cocaine reward memory are unknown. In this study, using a Pavlovian cocaine-induced conditioned place preference (CPP) procedure in rats, we tested the contribution of ubiquitin-proteasome system-dependent protein degradation in destabilization of cocaine reward memory. First, we found that polyubiquitinated protein expression levels and polyubiquitinated N-ethylmaleimide-sensitive fusion (NSF) markedly increased 15 min after retrieval while NSF protein levels decreased 1 h after retrieval in the synaptosomal membrane fraction in the nucleus accumbens (NAc) core. We then found that infusion of the proteasome inhibitor lactacystin into the NAc core prevented the impairment of memory reconsolidation induced by the protein synthesis inhibitor anisomycin and reversed the effects of anisomycin on NSF and glutamate receptor 2 (GluR2) protein levels in the synaptosomal membrane fraction in the NAc core. We also found that lactacystin infusion into the NAc core but not into the shell immediately after extinction training sessions inhibited CPP extinction and reversed the extinction training-induced decrease in NSF and GluR2 in the synaptosomal membrane fraction in the NAc core. Finally, infusions of lactacystin by itself into the NAc core immediately after each training session or before the CPP retrieval test had no effect on the consolidation and retrieval of cocaine reward memory. These findings suggest that ubiquitin-proteasome system-dependent protein degradation is critical for retrieval-induced memory destabilization.

  8. Reducing neonatal mortality in India: critical role of access to emergency obstetric care.

    Directory of Open Access Journals (Sweden)

    Anu Rammohan

    Full Text Available BACKGROUND: Neonatal mortality currently accounts for 41% of all global deaths among children below five years. Despite recording a 33% decline in neonatal deaths between 2000 and 2009, about 900,000 neonates died in India in 2009. The decline in neonatal mortality is slower than in the post-neonatal period, and neonatal mortality rates have increased as a proportion of under-five mortality rates. Neonatal mortality rates are higher among rural dwellers of India, who make up at least two-thirds of India's population. Identifying the factors influencing neonatal mortality will significantly improve child survival outcomes in India. METHODS: Our analysis is based on household data from the nationally representative 2008 Indian District Level Household Survey (DLHS-3. We use probit regression techniques to analyse the links between neonatal mortality at the household level and households' access to health facilities. The probability of the child dying in the first month of birth is our dependent variable. RESULTS: We found that 80% of neonatal deaths occurred within the first week of birth, and that the probability of neonatal mortality is significantly lower when the child's village is closer to the district hospital (DH, suggesting the critical importance of specialist hospital care in the prevention of newborn deaths. Neonatal deaths were lower in regions where emergency obstetric care was available at the District Hospitals. We also found that parental schooling and household wealth status improved neonatal survival outcomes. CONCLUSIONS: Addressing the main causes of neonatal deaths in India--preterm deliveries, asphyxia, and sepsis--requires adequacy of specialised workforce and facilities for delivery and neonatal intensive care and easy access by mothers and neonates. The slow decline in neonatal death rates reflects a limited attention to factors which contribute to neonatal deaths. The suboptimal quality and coverage of Emergency

  9. The role of gastrostomy tube placement in advanced dementia with dysphagia: a critical review

    Directory of Open Access Journals (Sweden)

    Goldberg LS

    2014-10-01

    Full Text Available Leanne S Goldberg,1 Kenneth W Altman2 1Department of Otolaryngology, Mount Sinai School of Medicine, New York, NY, USA; 2Baylor College of Medicine, Houston, TX, USAPurpose: Over 4.5 million people in North America had a diagnosis of dementia in the year 2000, and more than half had advanced disease with potential aspiration risk. There is much controversy regarding the use and timing of enteral feeding support in these patients with dysphagia. The management of dysphagia is far more complex when considering quality of life, “comfort care” hand feeding, the use of percutaneous endoscopic gastrostomy tube (PEG, and associated mortality rates. This study seeks to critically review the literature that evaluates PEG placement in this population. Methods: A systematic literature review of PubMed, from 1995–2012, was conducted to identify studies relating to PEG placement in dementia patients with dysphagia. The principal outcomes and related survival rates for this population were compared. Results: In total, 100 articles were identified in the search. Of these, ten met the search criteria and were analyzed. There was one study with a 2b level of evidence, one with 3b, and the remainder had level 4. All studies discussed long-term survival in the PEG versus non-PEG populations. No studies showed definitive evidence to suggest long-term survival rates improved in patients who underwent PEG placement as compared to those who did not. Two studies documented median survival worse in patients over age 80 with dementia and PEG placement.Conclusion: There is presently no evidence to suggest long-term survival rates improved in patients with advanced dementia who underwent PEG placement for dysphagia. Relevance to quality of life, need for nutrition and hydration, and ethical considerations in the decision process are discussed.Keywords: PEG, aspiration, elderly, feeding tube, swallow

  10. Local governments' roles of the compensation for damage by the Tokai JCO criticality accident

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Tomoyuki [Central Research Inst. of Electric Power Industry, Tokyo (Japan). Socio-Economic Research Center

    2003-03-01

    The Tokai JCO criticality accident on September 30, 1999 was the first case to which The Law on Compensation for Nuclear Damage was applied. Although the Law on Compensation for Nuclear Damage formulates the outline of the institutional framework for nuclear third party liability together with operator's insurance scheme, details of actual compensation procedure are not specified. By this reason, the compensation procedure in the Tokai accident had been executed without a concrete legal specification and a precedent. In spite of this situation, the compensation procedure with the accident led to an unexpectedly successful result. We observe the several reasons why the compensation procedure was implemented successfully despite the lack of concrete legal specification and a precedent. One of the reasons is that the local governments, Tokai Village and Ibaraki Prefecture, immediately took the leadership in implementing a temporary regime of compensation procedure without wasting time for waiting national government's directives. Upon practicing this compensation procedure, the local governments implemented the following steps. (1) Initial estimation of the amount and scope of damage. (2) Providing the criteria and heads of damage subject to compensation. (3) Unitary compensation procedure at the local levels. (4) Distribution of emergency payments for the victims. (5) Facilitating compensatory negotiation between the victims and JCO as arbitrator. However, some concerns are also pointed out about the fact that the local government directed the whole procedure without sufficient adjustment with the national government for compensation policy. Among all, in the compensation led by the local governments, it was difficult to guarantee fairness of compensation because victims who are influential on the local government such as industrial associations would have unfairly strong negotiation power in the compensatory negotiation, while the operator being

  11. Local governments' roles of the compensation for damage by the Tokai JCO criticality accident

    International Nuclear Information System (INIS)

    Tanabe, Tomoyuki

    2003-01-01

    The Tokai JCO criticality accident on September 30, 1999 was the first case to which The Law on Compensation for Nuclear Damage was applied. Although the Law on Compensation for Nuclear Damage formulates the outline of the institutional framework for nuclear third party liability together with operator's insurance scheme, details of actual compensation procedure are not specified. By this reason, the compensation procedure in the Tokai accident had been executed without a concrete legal specification and a precedent. In spite of this situation, the compensation procedure with the accident led to an unexpectedly successful result. We observe the several reasons why the compensation procedure was implemented successfully despite the lack of concrete legal specification and a precedent. One of the reasons is that the local governments, Tokai Village and Ibaraki Prefecture, immediately took the leadership in implementing a temporary regime of compensation procedure without wasting time for waiting national government's directives. Upon practicing this compensation procedure, the local governments implemented the following steps. (1) Initial estimation of the amount and scope of damage. (2) Providing the criteria and heads of damage subject to compensation. (3) Unitary compensation procedure at the local levels. (4) Distribution of emergency payments for the victims. (5) Facilitating compensatory negotiation between the victims and JCO as arbitrator. However, some concerns are also pointed out about the fact that the local government directed the whole procedure without sufficient adjustment with the national government for compensation policy. Among all, in the compensation led by the local governments, it was difficult to guarantee fairness of compensation because victims who are influential on the local government such as industrial associations would have unfairly strong negotiation power in the compensatory negotiation, while the operator being responsible for the

  12. Expanding the role of reactive transport models in critical zone processes

    Science.gov (United States)

    Li, Li; Maher, Kate; Navarre-Sitchler, Alexis; Druhan, Jennifer; Meile, Christof; Lawrence, Corey; Moore, Joel; Perdrial, Julia; Sullivan, Pamela; Thompson, Aaron; Jin, Lixin; Bolton, Edward W.; Brantley, Susan L.; Dietrich, William E.; Mayer, K. Ulrich; Steefel, Carl; Valocchi, Albert J.; Zachara, John M.; Kocar, Benjamin D.; McIntosh, Jennifer; Tutolo, Benjamin M.; Kumar, Mukesh; Sonnenthal, Eric; Bao, Chen; Beisman, Joe

    2017-01-01

    Models test our understanding of processes and can reach beyond the spatial and temporal scales of measurements. Multi-component Reactive Transport Models (RTMs), initially developed more than three decades ago, have been used extensively to explore the interactions of geothermal, hydrologic, geochemical, and geobiological processes in subsurface systems. Driven by extensive data sets now available from intensive measurement efforts, there is a pressing need to couple RTMs with other community models to explore non-linear interactions among the atmosphere, hydrosphere, biosphere, and geosphere. Here we briefly review the history of RTM development, summarize the current state of RTM approaches, and identify new research directions, opportunities, and infrastructure needs to broaden the use of RTMs. In particular, we envision the expanded use of RTMs in advancing process understanding in the Critical Zone, the veneer of the Earth that extends from the top of vegetation to the bottom of groundwater. We argue that, although parsimonious models are essential at larger scales, process-based models offer tools to explore the highly nonlinear coupling that characterizes natural systems. We present seven testable hypotheses that emphasize the unique capabilities of process-based RTMs for (1) elucidating chemical weathering and its physical and biogeochemical drivers; (2) understanding the interactions among roots, micro-organisms, carbon, water, and minerals in the rhizosphere; (3) assessing the effects of heterogeneity across spatial and temporal scales; and (4) integrating the vast quantity of novel data, including “omics” data (genomics, transcriptomics, proteomics, metabolomics), elemental concentration and speciation data, and isotope data into our understanding of complex earth surface systems. With strong support from data-driven sciences, we are now in an exciting era where integration of RTM framework into other community models will facilitate process

  13. Possible roles for corticosterone and critical size in the fledging of nestling pied flycatchers.

    Science.gov (United States)

    Kern, M; Bacon, W; Long, D; Cowie, R J

    2001-01-01

    Our study was designed to see whether corticosterone (B) rises abruptly in the blood of nestling pied flycatchers (Ficedula hypoleuca) at the time they fledge, as reported recently for kestrels, and if so, why. We measured the growth and blood levels of B and selected nutrients of nestlings in broods of five, seven, and nine chicks during 1998 and 1999. In half of the broods, we clipped selected wing and tail feathers of both parents with the intention of making it more difficult for them to provide their chicks with food. We collected blood samples when the chicks were six to 10 d old (period of rapid growth) and 15 d of age or older (0-5 d before fledging). B increased substantially several days before the chicks left the nest and then declined somewhat. We found no differences in rates of growth or blood levels of B, nutrients, and hematocrit as a function of either brood size or parental handicapping. Nestlings within a day of fledging appear to have been food deprived in 1998; their glucose was significantly reduced, and B, free fatty acids, and glycerol were significantly elevated compared to levels in chicks 1-4 d younger. Such changes did not occur in 1999. Blood levels of B were significantly correlated with brood size near the day of fledging, but not earlier, in both years of the study. It was possible to predict the day on which chicks would leave the nest, using their wing length when 12 d old. These results suggest that high blood levels of B associated with food restriction and sibling competition induce chicks to fledge, provided they have reached a critical size, and that the importance of fasting, sibling competition, and B may vary from year to year.

  14. DMPD: Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of health and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available and nucleotide oligomerisation domain inthe regulation of health and disease. Pu...bmedID 17535871 Title Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of health...17535871 Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of heal...th and disease. Mitchell JA, Paul-Clark MJ, Clarke GW, McMaster SK, Cartwright N. J

  15. A critical role of the nuclear receptor HR3 in regulation of gonadotrophic cycles of the mosquito Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Daniel Mane-Padros

    Full Text Available The orphan nuclear receptor HR3 is essential for developmental switches during insect development and metamorphosis regulated by 20-hydroxyecdysone (20E. Reproduction of female mosquitoes of the major vector of Dengue fever, Aedes aegypti, is cyclic because of its dependence on blood feeding. 20E is an important hormone regulating vitellogenic events in this mosquito; however, any role for HR3 in 20E-driven reproductive events has not been known. Using RNA interference (RNAi approach, we demonstrated that Aedes HR3 plays a critical role in a timely termination of expression of the vitellogenin (Vg gene encoding the major yolk protein precursor. It is also important for downregulation of the Target-of-Rapamycin pathway and activation of programmed autophagy in the Aedes fat body at the end of vitellogenesis. HR3 is critical in activating betaFTZ-F1, EcRB and USPA, the expressions of which are highly elevated at the end of vitellogenesis. RNAi depletion of HR3 (iHR3 prior to the first gonadotrophic cycle affects a normal progression of the second gonadotrophic cycle. Most of ovaries 24 h post second blood meal from iHR3 females in the second cycle were small with follicles that were only slightly different in length from of those of resting stage. In addition, these iHR3 females laid a significantly reduced number of eggs per mosquito as compared to those of iMal and the wild type. Our results indicate an important role of HR3 in regulation of 20E-regulated developmental switches during reproductive cycles of A. aegypti females.

  16. A nonspecific Setaria italica lipid transfer protein gene plays a critical role under abiotic stress

    Directory of Open Access Journals (Sweden)

    Yanlin Pan

    2016-11-01

    Full Text Available Lipid transfer proteins (LTPs are a class of cysteine-rich soluble proteins having small molecular weights. LTPs participate in flower and seed development, cuticular wax deposition, also play important roles in pathogen and abiotic stress responses. A nonspecific LTP gene (SiLTP was isolated from a foxtail millet (Setaria italica suppression subtractive hybridization (SSH library enriched for differentially expressed genes after abiotic stress treatments. A semi-quantitative reverse transcriptase PCR analysis showed that SiLTP was expressed in all foxtail millet tissues. Additionally, the SiLTP promoter drove GUS expression in root tips, stems, leaves, flowers and siliques of transgenic Arabidopsis. Quantitative real-time PCR indicated that the SiLTP expression was induced by NaCl, polyethylene glycol and abscisic acid. SiLTP was localized in the cytoplasm of tobacco leaf epidermal cells and maize protoplasts. The ectopic expression of SiLTP in tobacco resulted in higher levels of salt and drought tolerance than in the wild type (WT. To further assess the function of SiLTP, SiLTP overexpression (OE and RNA interference (RNAi-based transgenic foxtail millet were obtained. SiLTP-OE lines performed better under salt and drought stresses compared with WT plants. In contrast, the RNAi lines were much more sensitive to salt and drought compared than WT. Electrophoretic mobility shift assays and yeast one-hybrids indicated that the transcription factor (TF ABA-responsive DRE-binding protein (SiARDP could bind to the dehydration-responsive element of SiLTP promoter in vitro and in vivo, respectively. Moreover, the SiLTP expression levels were higher in SiARDP-OE plants compared than the WT. These results confirmed that SiLTP plays important roles in improving salt and drought stress tolerance of foxtail millet, and may partly be up-regulated by SiARDP. SiLTP may provide an effective genetic resource for molecular breeding in crops to enhance salt and

  17. The role of short-term memory and visuo-spatial skills in numerical magnitude processing: Evidence from Turner syndrome.

    Directory of Open Access Journals (Sweden)

    Lucie Attout

    Full Text Available Most studies on magnitude representation have focused on the visual modality with no possibility of disentangling the influence of visuo-spatial skills and short-term memory (STM abilities on quantification processes. This study examines this issue in patients with Turner syndrome (TS, a genetic condition characterized by a specific cognitive profile frequently associating poor mathematical achievement, low spatial skills and reduced STM abilities. In order to identify the influence of visuo-spatial and STM processing on numerical magnitude abilities, twenty female participants with TS and twenty control female participants matched for verbal IQ and education level were administered a series of magnitude comparison tasks. The tasks differed on the nature of the magnitude to be processed (continuous, discrete and symbolic magnitude, on visuo-spatial processing requirement (no/high and on STM demands (low in simultaneous presentation vs. high in sequential presentation. Our results showed a lower acuity when participants with TS compared the numerical magnitudes of stimuli presented sequentially (low visuo-spatial processing and high STM load: Dot sequence and Sound sequence while no difference was observed in the numerical comparison of sets presented simultaneously. In addition, the group difference in sequential tasks disappeared when controlling for STM abilities. Finally, both groups demonstrated similar performance when comparing continuous or symbolic magnitude stimuli and they exhibited comparable subitizing abilities. These results highlight the importance of STM abilities in extracting numerosity through a sequential presentation and underline the importance of considering the impact of format presentation on magnitude judgments.

  18. Reviews and syntheses: on the roles trees play in building and plumbing the critical zone

    Directory of Open Access Journals (Sweden)

    S. L. Brantley

    2017-11-01

    Full Text Available Trees, the most successful biological power plants on earth, build and plumb the critical zone (CZ in ways that we do not yet understand. To encourage exploration of the character and implications of interactions between trees and soil in the CZ, we propose nine hypotheses that can be tested at diverse settings. The hypotheses are roughly divided into those about the architecture (building and those about the water (plumbing in the CZ, but the two functions are intertwined. Depending upon one's disciplinary background, many of the nine hypotheses listed below may appear obviously true or obviously false. (1 Tree roots can only physically penetrate and biogeochemically comminute the immobile substrate underlying mobile soil where that underlying substrate is fractured or pre-weathered. (2 In settings where the thickness of weathered material, H, is large, trees primarily shape the CZ through biogeochemical reactions within the rooting zone. (3 In forested uplands, the thickness of mobile soil, h, can evolve toward a steady state because of feedbacks related to root disruption and tree throw. (4 In settings where h ≪ H and the rates of uplift and erosion are low, the uptake of phosphorus into trees is buffered by the fine-grained fraction of the soil, and the ultimate source of this phosphorus is dust. (5 In settings of limited water availability, trees maintain the highest length density of functional roots at depths where water can be extracted over most of the growing season with the least amount of energy expenditure. (6 Trees grow the majority of their roots in the zone where the most growth-limiting resource is abundant, but they also grow roots at other depths to forage for other resources and to hydraulically redistribute those resources to depths where they can be taken up more efficiently. (7 Trees rely on matrix water in the unsaturated zone that at times may have an isotopic composition distinct from the gravity

  19. Reviews and syntheses: on the roles trees play in building and plumbing the critical zone

    Science.gov (United States)

    Brantley, Susan L.; Eissenstat, David M.; Marshall, Jill A.; Godsey, Sarah E.; Balogh-Brunstad, Zsuzsanna; Karwan, Diana L.; Papuga, Shirley A.; Roering, Joshua; Dawson, Todd E.; Evaristo, Jaivime; Chadwick, Oliver; McDonnell, Jeffrey J.; Weathers, Kathleen C.

    2017-11-01

    Trees, the most successful biological power plants on earth, build and plumb the critical zone (CZ) in ways that we do not yet understand. To encourage exploration of the character and implications of interactions between trees and soil in the CZ, we propose nine hypotheses that can be tested at diverse settings. The hypotheses are roughly divided into those about the architecture (building) and those about the water (plumbing) in the CZ, but the two functions are intertwined. Depending upon one's disciplinary background, many of the nine hypotheses listed below may appear obviously true or obviously false. (1) Tree roots can only physically penetrate and biogeochemically comminute the immobile substrate underlying mobile soil where that underlying substrate is fractured or pre-weathered. (2) In settings where the thickness of weathered material, H, is large, trees primarily shape the CZ through biogeochemical reactions within the rooting zone. (3) In forested uplands, the thickness of mobile soil, h, can evolve toward a steady state because of feedbacks related to root disruption and tree throw. (4) In settings where h ≪ H and the rates of uplift and erosion are low, the uptake of phosphorus into trees is buffered by the fine-grained fraction of the soil, and the ultimate source of this phosphorus is dust. (5) In settings of limited water availability, trees maintain the highest length density of functional roots at depths where water can be extracted over most of the growing season with the least amount of energy expenditure. (6) Trees grow the majority of their roots in the zone where the most growth-limiting resource is abundant, but they also grow roots at other depths to forage for other resources and to hydraulically redistribute those resources to depths where they can be taken up more efficiently. (7) Trees rely on matrix water in the unsaturated zone that at times may have an isotopic composition distinct from the gravity-drained water that transits

  20. The role of rock moisture on regulating hydrologic and solute fluxes in the critical zone

    Science.gov (United States)

    Rempe, D. M.; Druhan, J. L.; Hahm, W. J.; Wang, J.; Murphy, C.; Cargill, S.; Dietrich, W. E.; Tune, A. K.

    2017-12-01

    In environments where the vadose zone extends below the soil layer into underlying weathered bedrock, the water held in the weathering -generated pores can be an important source of moisture to vegetation. The heterogeneous distribution of pore space in weathered bedrock, furthermore, controls the subsurface water flowpaths that dictate how water is partitioned in the critical zone (CZ) and evolves geochemically. Here, we present the results of direct monitoring of the fluxes of water and solutes through the deep CZ using a novel vadose zone monitoring system (VMS) as well as geophysical logging and sampling in a network of deep wells across a steep hillslope in Northern California. At our study site (Eel River CZO), multi-year monitoring reveals that a significant fraction of incoming rainfall (up to 30%) is seasonally stored in the fractures and matrix of the upper 12 m of weathered bedrock as rock moisture. Intensive geochemical and geophysical observations distributed from the surface to the depth of unweathered bedrock indicate that the seasonal addition and depletion of rock moisture has key implications for hydrologic and geochemical processes. First, rock moisture storage provides an annually consistent water storage reservoir for use by vegetation during the summer, which buffers transpiration fluxes against variability in seasonal precipitation. Second, because the timing and magnitude of groundwater recharge and streamflow are controlled by the annual filling and drainage of the rock moisture, rock moisture regulates the partitioning of hydrologic fluxes. Third, we find that rock moisture dynamics—which influence the myriad geochemical and microbial processes that weather bedrock—strongly correspond with the observed vertical weathering profile. As a result of the coupling between chemical weathering reactions and hydrologic fluxes, the geochemical composition of groundwater and streamflow is influenced by the temporal dynamics of rock moisture. Our

  1. Critical role of c-Jun overexpression in liver metastasis of human breast cancer xenograft model

    International Nuclear Information System (INIS)

    Zhang, Yan; Hu, Meiru; Shen, Beifen; Guo, Ning; Pu, Xiaoyun; Shi, Ming; Chen, Liyong; Song, Yuhua; Qian, Lu; Yuan, Guogang; Zhang, Hao; Yu, Ming

    2007-01-01

    c-Jun/AP-1 has been linked to invasive properties of aggressive breast cancer. Recently, it has been reported that overexpression of c-Jun in breast cancer cell line MCF-7 resulted in increased AP-1 activity, motility and invasiveness of the cells in vitro and tumor formation in nude mice. However, the role of c-Jun in metastasis of human breast cancer in vivo is currently unknown. To further investigate the direct involvement of c-Jun in tumorigenesis and metastasis, in the present study, the effects of c-Jun overexpression were studied in both in vitro and in nude mice. Ectopic overexpression of c-Jun promoted the growth of MCF-7 cells and resulted in a significant increase in the percentage of cells in S phase and increased motility and invasiveness. Introduction of c-Jun gene alone into weakly invasive MCF-7 cells resulted in the transfected cells capable of metastasizing to the nude mouse liver following tail vein injection. The present study confirms that overexpression of c-Jun contributes to a more invasive phenotype in MCF-7 cells. It indicates an interesting relationship between c-Jun expression and increased property of adhesion, migration and in vivo liver metastasis of MCF-7/c-Jun cells. The results provide further evidence that c-Jun is involved in the metastasis of breast cancer. The finding also opens an opportunity for development of anti-c-Jun strategies in breast cancer therapy

  2. Critical roles for a genetic code alteration in the evolution of the genus Candida.

    Science.gov (United States)

    Silva, Raquel M; Paredes, João A; Moura, Gabriela R; Manadas, Bruno; Lima-Costa, Tatiana; Rocha, Rita; Miranda, Isabel; Gomes, Ana C; Koerkamp, Marian J G; Perrot, Michel; Holstege, Frank C P; Boucherie, Hélian; Santos, Manuel A S

    2007-10-31

    During the last 30 years, several alterations to the standard genetic code have been discovered in various bacterial and eukaryotic species. Sense and nonsense codons have been reassigned or reprogrammed to expand the genetic code to selenocysteine and pyrrolysine. These discoveries highlight unexpected flexibility in the genetic code, but do not elucidate how the organisms survived the proteome chaos generated by codon identity redefinition. In order to shed new light on this question, we have reconstructed a Candida genetic code alteration in Saccharomyces cerevisiae and used a combination of DNA microarrays, proteomics and genetics approaches to evaluate its impact on gene expression, adaptation and sexual reproduction. This genetic manipulation blocked mating, locked yeast in a diploid state, remodelled gene expression and created stress cross-protection that generated adaptive advantages under environmental challenging conditions. This study highlights unanticipated roles for codon identity redefinition during the evolution of the genus Candida, and strongly suggests that genetic code alterations create genetic barriers that speed up speciation.

  3. Critical Role of Endoplasmic Reticulum Stress in Cognitive Impairment Induced by Microcystin-LR

    Directory of Open Access Journals (Sweden)

    Fei Cai

    2015-11-01

    Full Text Available Recent studies showed that cyanobacteria-derived microcystin-leucine-arginine (MCLR can cause hippocampal pathological damage and trigger cognitive impairment; but the underlying mechanisms have not been well understood. The objective of the present study was to investigate the mechanism of MCLR-induced cognitive deficit; with a focus on endoplasmic reticulum (ER stress. The Morris water maze test and electrophysiological study demonstrated that MCLR caused spatial memory injury in male Wistar rats; which could be inhibited by ER stress blocker; tauroursodeoxycholic acid (TUDCA. Meanwhile; real-time polymerase chain reaction (real-time PCR and immunohistochemistry demonstrated that the expression level of the 78-kDa glucose-regulated protein (GRP78; C/EBP homologous protein (CHOP and caspase 12 were significantly up-regulated. These effects were rescued by co-administration of TUDCA. In agreement with this; we also observed that treatment of rats with TUDCA blocked the alterations in ER ultrastructure and apoptotic cell death in CA1 neurons from rats exposed to MCLR. Taken together; the present results suggested that ER stress plays an important role in potential memory impairments in rats treated with MCLR; and amelioration of ER stress may serve as a novel strategy to alleviate damaged cognitive function triggered by MCLR.

  4. Pediatric Obstructive Sleep Apnea and the critical role of oral-facial growth: evidences

    Directory of Open Access Journals (Sweden)

    Christian eGuilleminault

    2013-01-01

    Full Text Available Aims: Review of evidence in support of an oral-facial growth impairment in the development of pediatric sleep apnea in non-obese childrenMethod: Review of experimental data from infant monkeys with experimentally induced nasal resistance. Review of early historical data in the orthodontic literature indicating the abnormal oral-facial development associated with mouth breathing and nasal resistance. Review of the progressive demonstration of sleep disordered breathing in children who underwent incomplete treatment of OSA with adenotonsillectomy, and demonstration of abnormal oral-facial anatomy that must often to be treated in order for the resolution of OSA. Review of long term recurrence data on OSA and indication of oral-facial myofunctional dysfunction in association with the recurrence of OSA. Results: Presentation of prospective data on premature infants and sleep-disordered-breathing (SDB-treated children, supporting the concept of oral-facial hypotonia. Presentation of evidence supporting hypotonia as a primary element in the development of oral-facial anatomic abnormalities leading to abnormal breathing during sleep. Continuous interaction between oral facial muscle tone, maxillary-mandibular growth and development of SDB. Role of myofunctional re-education with orthodontics and elimination of upper airway soft tissue in the treatment of non-obese SDB children. Conclusion: Pediatric OSA in non-obese children is a disorder of oral facial growth.

  5. New inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism.

    Science.gov (United States)

    Meng, Fantao; Han, Yong; Srisai, Dollada; Belakhov, Valery; Farias, Monica; Xu, Yong; Palmiter, Richard D; Baasov, Timor; Wu, Qi

    2016-03-29

    Currently available inducible Cre/loxP systems, despite their considerable utility in gene manipulation, have pitfalls in certain scenarios, such as unsatisfactory recombination rates and deleterious effects on physiology and behavior. To overcome these limitations, we designed a new, inducible gene-targeting system by introducing an in-frame nonsense mutation into the coding sequence of Cre recombinase (nsCre). Mutant mRNAs transcribed from nsCre transgene can be efficiently translated into full-length, functional Cre recombinase in the presence of nonsense suppressors such as aminoglycosides. In a proof-of-concept model, GABA signaling from hypothalamic neurons expressing agouti-related peptide (AgRP) was genetically inactivated within 4 d after treatment with a synthetic aminoglycoside. Disruption of GABA synthesis in AgRP neurons in young adult mice led to a dramatic loss of body weight due to reduced food intake and elevated energy expenditure; they also manifested glucose intolerance. In contrast, older mice with genetic inactivation of GABA signaling by AgRP neurons had only transient reduction of feeding and body weight; their energy expenditure and glucose tolerance were unaffected. These results indicate that GABAergic signaling from AgRP neurons plays a key role in the control of feeding and metabolism through an age-dependent mechanism. This new genetic technique will augment current tools used to elucidate mechanisms underlying many physiological and neurological processes.

  6. Critical role of the FERM domain in Pyk2 stimulated glioma cell migration

    International Nuclear Information System (INIS)

    Lipinski, Christopher A.; Tran, Nhan L.; Dooley, Andrea; Pang, Yuan-Ping; Rohl, Carole; Kloss, Jean; Yang, Zhongbo; McDonough, Wendy; Craig, David; Berens, Michael E.; Loftus, Joseph C.

    2006-01-01

    The strong tendency of malignant glioma cells to invade locally into surrounding normal brain precludes effective surgical resection, reduces the efficacy of radiotherapy, and is associated with increased resistance to chemotherapy regimens. We report that the N-terminal FERM domain of Pyk2 regulates its promigratory function. A 3-dimensional model of the Pyk2 FERM domain was generated and mutagenesis studies identified residues essential for Pyk2 promigratory function. Model-based targeted mutations within the FERM domain decreased Pyk2 phosphorylation and reduced the capacity of Pyk2 to stimulate glioma cell migration but did not significantly alter the intracellular distribution of Pyk2. Expression of autonomous Pyk2 FERM domain fragments containing analogous mutations exhibited reduced capacity to inhibit glioma cell migration and Pyk2 phosphorylation relative to expression of an autonomous wild type FERM domain fragment. These results indicate that the FERM domain plays an important role in regulating the functional competency of Pyk2 as a promigratory factor in glioma

  7. Thiamine plays a critical role in the acid tolerance of Listeria monocytogenes.

    Science.gov (United States)

    Madeo, Moira; O'Riordan, Niamh; Fuchs, Thilo M; Utratna, Marta; Karatzas, Kimon Andreas G; O'Byrne, Conor P

    2012-01-01

    Understanding the molecular basis of acid tolerance in the food-borne pathogen Listeria monocytogenes is important as this property contributes to survival in the food-chain and enhances survival within infected hosts. The aim of this study was to identify genes contributing to acid tolerance in L. monocytogenes using transposon mutagenesis and subsequently to elucidate the physiological role of these genes in acid tolerance. One mutant harboring a Tn917 insertion in the thiT gene (formerly lmo1429), which encodes a thiamine (vitamin B1) uptake system, was found to be highly sensitive to acid. The acid-sensitive phenotype associated with loss of this gene was confirmed with an independently isolated mutant, from which the thiT gene was deleted (∆thiT). Cells of both wild-type and ∆thiT mutant that were thiamine depleted were found to be significantly more acid sensitive than control cultures. Thiamine-depleted cultures failed to produce significant concentrations of acetoin, consistent with the known thiamine dependence of acetolactate synthase, an enzyme required for acetoin synthesis from pyruvate. As acetoin synthesis is a proton-consuming process, we suggest that the acid sensitivity observed in thiamine-depleted cultures may be owing to an inability to produce acetoin. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  8. Spontaneous Formation of Nanopillar Arrays in Ultrathin Viscous Films: Critical Role of Thermocapillary Stresses

    Science.gov (United States)

    Troian, Sandra; Dietzel, Mathias

    2010-03-01

    Nanoscale structures manifest exceedingly large surface to volume ratios and are therefore highly susceptible to control by surface stresses. Actuation techniques which can exploit this feature provide a key strategy for construction and self-organization of large area arrays. During the past decade, several groups have reported that molten polymer nanofilms subject to an ultra-large transverse thermal gradient undergo spontaneous formation of nanopillar arrays. The prevailing explanation is that coherent interfacial reflection of acoustic phonons causes periodic modulation of the radiation pressure leading to instability and pillar growth. We demonstrate instead that thermocapillary forces play a crucial if not dominant role in the formation process due to the strong modulation of surface tension with temperature. Any nanoscale viscous film is prone to such formations, not just polymeric films. Analysis of the governing interface equation reveals the mechanism controlling the growth, spacing and symmetry of these self-assembling arrays. We discuss how these findings are being used in our laboratory to construct nanoscale components for optical and photonic applications.

  9. The possible critical role of T-cell help in DSA-mediated graft loss.

    Science.gov (United States)

    Süsal, Caner; Slavcev, Antonij; Pham, Lien; Zeier, Martin; Morath, Christian

    2018-06-01

    In this review, we discuss a possible central role of T-cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect. Patients positive for both pretransplant DSA and sCD30 appear to require special measures, such as the elimination of DSA from the circulation, potent immunosuppression, good HLA-matching, and intense post-transplant monitoring, whereas exclusion of DSA-positive patients from transplantation in the absence of high sCD30 may not be justified in all cases, even if the pretransplant DSA are strong and complement-activating. © 2018 Steunstichting ESOT.

  10. Pediatric obstructive sleep apnea and the critical role of oral-facial growth: evidences.

    Science.gov (United States)

    Huang, Yu-Shu; Guilleminault, Christian

    2012-01-01

    Review of evidence in support of an oral-facial growth impairment in the development of pediatric sleep apnea in non-obese children. Review of experimental data from infant monkeys with experimentally induced nasal resistance. Review of early historical data in the orthodontic literature indicating the abnormal oral-facial development associated with mouth breathing and nasal resistance. Review of the progressive demonstration of sleep-disordered-breathing (SDB) in children who underwent incomplete treatment of OSA with adenotonsillectomy, and demonstration of abnormal oral-facial anatomy that must often be treated in order for the resolution of OSA. Review of data of long-term recurrence of OSA and indication of oral-facial myofunctional dysfunction in association with the recurrence of OSA. Presentation of prospective data on premature infants and SDB-treated children, supporting the concept of oral-facial hypotonia. Presentation of evidence supporting hypotonia as a primary element in the development of oral-facial anatomic abnormalities leading to abnormal breathing during sleep. Continuous interaction between oral-facial muscle tone, maxillary-mandibular growth and development of SDB. Role of myofunctional reeducation with orthodontics and elimination of upper airway soft tissue in the treatment of non-obese SDB children. Pediatric OSA in non-obese children is a disorder of oral-facial growth.

  11. A critical role of CDKN3 in Bcr-Abl-mediated tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Qinghuang Chen

    Full Text Available CDKN3 (cyclin-dependent kinase inhibitor 3, a dual specificity protein phosphatase, dephosphorylates cyclin-dependent kinases (CDKs and thus functions as a key negative regulator of cell cycle progression. Deregulation or mutations of CDNK3 have been implicated in various cancers. However, the role of CDKN3 in Bcr-Abl-mediated chronic myelogenous leukemia (CML remains unknown. Here we found that CDKN3 acts as a tumor suppressor in Bcr-Abl-mediated leukemogenesis. Overexpression of CDKN3 sensitized the K562 leukemic cells to imanitib-induced apoptosis and dramatically inhibited K562 xenografted tumor growth in nude mouse model. Ectopic expression of CDKN3 significantly reduced the efficiency of Bcr-Abl-mediated transformation of FDCP1 cells to growth factor independence. In contrast, depletion of CDKN3 expression conferred resistance to imatinib-induced apoptosis in the leukemic cells and accelerated the growth of xenograph leukemia in mice. In addition, we found that CDKN3 mutant (CDKN3-C140S devoid of the phosphatase activity failed to affect the K562 leukemic cell survival and xenografted tumor growth, suggesting that the phosphatase of CDKN3 was required for its tumor suppressor function. Furthermore, we observed that overexpression of CDKN3 reduced the leukemic cell survival by dephosphorylating CDK2, thereby inhibiting CDK2-dependent XIAP expression. Moreover, overexpression of CDKN3 delayed G1/S transition in K562 leukemic cells. Our results highlight the importance of CDKN3 in Bcr-Abl-mediated leukemogenesis, and provide new insights into diagnostics and therapeutics of the leukemia.

  12. Critical role of oxygen radicals in the initiation of hepatic depression after trauma hemorrhage.

    Science.gov (United States)

    Jarrar, D; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

    2000-11-01

    Although depression in hepatocellular function occurs early after trauma and severe hemorrhage and persists despite fluid resuscitation, it remains unknown whether reactive oxygen species (ROS) play any role in the initiation of hepatocellular depression and damage under those conditions. We hypothesized that administration of a ROS scavenger at the beginning of resuscitation will attenuate organ injury after severe shock. Male Sprague-Dawley rats (275-325 g) underwent laparotomy (i.e., induction of soft tissue trauma) and were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal bleed-out volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of maximal bleed-out with RL over 60 minutes. The ROS scavenger 2-mercaptopropionyl glycine (30 mg/kg) or vehicle was administered intravenously as a bolus at the beginning of resuscitation. At 2 hours after the completion of crystalloid resuscitation or the equivalent interval after sham-operation, cardiac index was measured by a dye dilution technique. Hepatocellular function, i.e., the maximum velocity of indocyanine green clearance (Vmax) and the efficiency of the active transport (Km), was determined using an in vivo hemoreflectometer. Serum levels of tumor necrosis factor (TNF)-alpha and alanine aminotransferase were determined with ELISA and colorimetrically, respectively. The results indicate that at 2 hours after trauma hemorrhage and resuscitation, cardiac index and hepatocellular function were markedly depressed with concomitantly increased serum levels of TNF-alpha and alanine aminotransferase (p hepatic function and markedly attenuated liver enzyme release and serum levels of TNF-alpha (p trauma hemorrhage and resuscitation.

  13. The critical role of ERK in death resistance and invasiveness of hypoxia-selected glioblastoma cells

    International Nuclear Information System (INIS)

    Kim, Jee-Youn; Kim, Yong-Jun; Lee, Sun; Park, Jae-Hoon

    2009-01-01

    The rapid growth of tumor parenchyma leads to chronic hypoxia that can result in the selection of cancer cells with a more aggressive behavior and death-resistant potential to survive and proliferate. Thus, identifying the key molecules and molecular mechanisms responsible for the phenotypic changes associated with chronic hypoxia has valuable implications for the development of a therapeutic modality. The aim of this study was to identify the molecular basis of the phenotypic changes triggered by chronic repeated hypoxia. Hypoxia-resistant T98G (HRT98G) cells were selected by repeated exposure to hypoxia and reoxygenation. Cell death rate was determined by the trypan blue exclusion method and protein expression levels were examined by western blot analysis. The invasive phenotype of the tumor cells was determined by the Matrigel invasion assay. Immunohistochemistry was performed to analyze the expression of proteins in the brain tumor samples. The Student T-test and Pearson Chi-Square test was used for statistical analyses. We demonstrate that chronic repeated hypoxic exposures cause T98G cells to survive low oxygen tension. As compared with parent cells, hypoxia-selected T98G cells not only express higher levels of anti-apoptotic proteins such as Bcl-2, Bcl-X L , and phosphorylated ERK, but they also have a more invasive potential in Matrigel invasion chambers. Activation or suppression of ERK pathways with a specific activator or inhibitor, respectively, indicates that ERK is a key molecule responsible for death resistance under hypoxic conditions and a more invasive phenotype. Finally, we show that the activation of ERK is more prominent in malignant glioblastomas exposed to hypoxia than in low grade astrocytic glial tumors. Our study suggests that activation of ERK plays a pivotal role in death resistance under chronic hypoxia and phenotypic changes related to the invasive phenotype of HRT98G cells compared to parent cells

  14. A case report of pseudo grey platelet syndrome with citrate-induced pseudothrombocytopenia: those artifacts may interfere in the platelet numeration and lead to critical misdiagnosis.

    Science.gov (United States)

    Herb, Agathe; Maurer, Maxime; Alamome, Isabelle; Bihl, Pierre-Adrien; Ghiura, Cosmina; Hurstel, Rémy

    2017-08-01

    The pseudo grey platelet syndrome is a rare artifact due to the degranulation of platelets caused, in vitro, by EDTA. This phenomenon is likely to disturb the platelet numeration and it is essential not to mistake it for a grey syndrome platelet, which is a constitutional thrombopathy with macrothrombopenia, in order to avoid specialized tests, or even misdiagnosis. Indeed, these two entities are cytologically alike, as grey platelets are found on the blood smear of a sample collected on EDTA in both cases. We here describe the case of a patient admitted in Colmar's Hospital for a chronic thrombocytopenia, associating both a pseudothrombocytopenia and a pseudo grey platelet syndrome.

  15. Critical role of CDK11p58 in human breast cancer growth and angiogenesis

    International Nuclear Information System (INIS)

    Chi, Yayun; Huang, Sheng; Peng, Haojie; Liu, Mengying; Zhao, Jun; Shao, Zhiming; Wu, Jiong

    2015-01-01

    A capillary network is needed in cancer growth and metastasis. Induction of angiogenesis represents one of the major hallmarks of cancer. CDK11 p58 , a Ser/Thr kinase that belongs to the Cell Division Cycle 2-like 1 (CDC2L1) subfamily is associated with cell cycle progression, tumorigenesis, sister chromatid cohesion and apoptotic signaling. However, its role in breast cancer proliferation and angiogenesis remains unclear. Tumorigenicity assays and blood vessel assessment in athymic mice were used to assess the function of CDK11 p58 in tumor proliferation and angiogenesis. CCK-8 assay was used to detect breast cancer cell growth. Immunohistochemistry was used to detect the expression of vascular endothelial growth factor (VEGF), CD31 and CD34 in CDK11 positive patient breast cancer tissues. Dual-Luciferase array was used to analyze the function of CDK11 p58 in the regulation of VEGF promoter activity. Western blot was used to detect related protein expression levels. CDK11 p58 inhibited breast cancer growth and angiogenesis in breast cancer cells and in nude mice transplanted with tumors. Immunohistochemistry confirmed that CDK11 p58 was negatively associated with angiogenesis-related proteins such as VEGF, CD31 and CD34 in breast cancer patients. Real-time PCR and dual-luciferase assay showed CDK11 p58 inhibited the mRNA levels of VEGF and the promoter activity of VEGF. As CDK11 p58 is a Ser/Thr kinase, the kinase-dead mutant failed to inhibit VEGF mRNA and promoter activity. Western blot analysis showed the same pattern of related protein expression. The data suggested angiogenesis inhibition was dependent on CDK11 p58 kinase activity. This study indicates that CDK11 p58 inhibits the growth and angiogenesis of breast cancer dependent on its kinase activity. The online version of this article (doi:10.1186/s12885-015-1698-7) contains supplementary material, which is available to authorized users

  16. Critical role of CCDC6 in the neoplastic growth of testicular germ cell tumors

    International Nuclear Information System (INIS)

    Staibano, Stefania; Fusco, Alfredo; Chieffi, Paolo; Celetti, Angela; Ilardi, Gennaro; Leone, Vincenza; Luise, Chiara; Merolla, Francesco; Esposito, Francesco; Morra, Francesco; Siano, Maria; Franco, Renato

    2013-01-01

    DNA damage response has been clearly described as an anti-cancer barrier in early human tumorigenesis. Moreover, interestingly, testicular germ cell tumors (TGCTs) have been reported to lack the DNA Damage Response (DDR) pathway activation. CCDC6 is a pro-apoptotic phosphoprotein substrate of the kinase ataxia telangectasia mutated (ATM) able to sustain DNA damage checkpoint in response to genotoxic stress and is commonly rearranged in malignancies upon fusion with different partners. In our study we sought to determine whether CCDC6 could have a role in the patho-genesis of testicular germ cell tumors. To achieve this aim, analysis for CCDC6 expression has been evaluated on serial sections of the mouse testis by immunohistochemistry and on separate populations of murine testicular cells by western blot. Next, the resistance to DNA damage-induced apoptosis and the production of reactive oxygen species has been investigated in GC1 cells, derived from immortalized type B murine germ cells, following CCDC6 silencing. Finally, the CCDC6 expression in normal human testicular cells, in Intratubular Germ Cell Neoplasia Unclassified (IGCNU), in a large series of male germ cell tumours and in the unique human seminoma TCam2 cell line has been evaluated by immunohistochemistry and by Western Blot analyses. The analysis of the CCDC6 expression revealed its presence in Sertoli cells and in spermatogonial cells. CCDC6 loss was the most consistent feature among the primary tumours and TCam2 cells. Interestingly, following treatment with low doses of H 2 O 2 , the silencing of CCDC6 in GC1 cells caused a decrease in the oxidized form of cytochrome c and low detection of Bad, PARP-1 and Caspase 3 proteins. Moreover, in the silenced cells, upon oxidative damage, the cell viability was protected, the γH2AX activation was impaired and the Reactive Oxygen Species (ROS) release was decreased. Therefore, our results suggest that the loss of CCDC6 could aid the spermatogonial cells to

  17. Nanoimprinted backside reflectors for a-Si:H thin-film solar cells: critical role of absorber front textures.

    Science.gov (United States)

    Tsao, Yao-Chung; Fisker, Christian; Pedersen, Thomas Garm

    2014-05-05

    The development of optimal backside reflectors (BSRs) is crucial for future low cost and high efficiency silicon (Si) thin-film solar cells. In this work, nanostructured polymer substrates with aluminum coatings intended as BSRs were produced by positive and negative nanoimprint lithography (NIL) techniques, and hydrogenated amorphous silicon (a-Si:H) was deposited hereon as absorbing layers. The relationship between optical properties and geometry of front textures was studied by combining experimental reflectance spectra and theoretical simulations. It was found that a significant height variation on front textures plays a critical role for light-trapping enhancement in solar cell applications. As a part of sample preparation, a transfer NIL process was developed to overcome the problem of low heat deflection temperature of polymer substrates during solar cell fabrication.

  18. Suppressing Structural Colors of Photocatalytic Optical Coatings on Glass: The Critical Role of SiO2.

    Science.gov (United States)

    Li, Ronghua; Boudot, Mickael; Boissière, Cédric; Grosso, David; Faustini, Marco

    2017-04-26

    The appearance of structural colors on coated-glass is a critical esthetical drawback toward industrialization of photocatalytic coatings on windows for architecture or automobile. Herein we describe a rational approach to suppress the structural color of mesoporous TiO 2 -based coatings preserving photoactivity and mechanical stiffness. Addition of SiO 2 as third component is discussed. Ti x Si (1-x) O 2 mesoporous coatings were fabricated by one-step liquid deposition process through the evaporation induced self-assembling and characterized by GI-SAXS, GI-WAXS, electron microscopies, and in situ Environmental Ellipsometry Porosimetry. Guided by optical simulation, we investigated the critical role of SiO 2 on the optical responses of the films but also on the structural, mechanical, and photocatalytic properties, important requirements to go toward real applications. We demonstrate that adding SiO 2 to porous TiO 2 allows tuning and suppression of structural colors through refractive index matching and up to 160% increase in mechanical stiffening of the films. This study leads us to demonstrate an example of "invisible" coating, in which the light reflection is angle- and thickness-independent, and exhibiting high porosity, mechanical stiffness, and photoactivity.

  19. Ending on a positive: Examining the role of safety leadership decisions, behaviours and actions in a safety critical situation.

    Science.gov (United States)

    Donovan, Sarah-Louise; Salmon, Paul M; Horberry, Timothy; Lenné, Michael G

    2018-01-01

    Safety leadership is an important factor in supporting safe performance in the workplace. The present case study examined the role of safety leadership during the Bingham Canyon Mine high-wall failure, a significant mining incident in which no fatalities or injuries were incurred. The Critical Decision Method (CDM) was used in conjunction with a self-reporting approach to examine safety leadership in terms of decisions, behaviours and actions that contributed to the incidents' safe outcome. Mapping the analysis onto Rasmussen's Risk Management Framework (Rasmussen, 1997), the findings demonstrate clear links between safety leadership decisions, and emergent behaviours and actions across the work system. Communication and engagement based decisions featured most prominently, and were linked to different leadership practices across the work system. Further, a core sub-set of CDM decision elements were linked to the open flow and exchange of information across the work system, which was critical to supporting the safe outcome. The findings provide practical implications for the development of safety leadership capability to support safety within the mining industry. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. A microarray of ubiquitylated proteins for profiling deubiquitylase activity reveals the critical roles of both chain and substrate.

    Science.gov (United States)

    Loch, Christian M; Strickler, James E

    2012-11-01

    Substrate ubiquitylation is a reversible process critical to cellular homeostasis that is often dysregulated in many human pathologies including cancer and neurodegeneration. Elucidating the mechanistic details of this pathway could unlock a large store of information useful to the design of diagnostic and therapeutic interventions. Proteomic approaches to the questions at hand have generally utilized mass spectrometry (MS), which has been successful in identifying both ubiquitylation substrates and profiling pan-cellular chain linkages, but is generally unable to connect the two. Interacting partners of the deubiquitylating enzymes (DUBs) have also been reported by MS, although substrates of catalytically competent DUBs generally cannot be. Where they have been used towards the study of ubiquitylation, protein microarrays have usually functioned as platforms for the identification of substrates for specific E3 ubiquitin ligases. Here, we report on the first use of protein microarrays to identify substrates of DUBs, and in so doing demonstrate the first example of microarray proteomics involving multiple (i.e., distinct, sequential and opposing) enzymatic activities. This technique demonstrates the selectivity of DUBs for both substrate and type (mono- versus poly-) of ubiquitylation. This work shows that the vast majority of DUBs are monoubiquitylated in vitro, and are incapable of removing this modification from themselves. This work also underscores the critical role of utilizing both ubiquitin chains and substrates when attempting to characterize DUBs. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    International Nuclear Information System (INIS)

    Doi, Keiko; Fujimoto, Takahiro; Okamura, Tadashi; Ogawa, Masahiro; Tanaka, Yoko; Mototani, Yasumasa; Goto, Motohito; Ota, Takeharu; Matsuzaki, Hiroshi; Kuroki, Masahide; Tsunoda, Toshiyuki; Sasazuki, Takehiko; Shirasawa, Senji

    2012-01-01

    Highlights: ► We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. ► Zfat-deficiency leads to reduction in the number of the peripheral T cells. ► Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. ► Decreased expression of IL-7Rα, IL-2Rα and IL-2 in Zfat-deficient peripheral T cells. ► Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7Rα and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2Rα expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  2. A whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Xu

    2011-12-01

    Full Text Available Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into "whole-body" contextual models that mimic in vivo conditions.

  3. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

    Directory of Open Access Journals (Sweden)

    Gang Xin

    2015-11-01

    Full Text Available Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue “unhelped” CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells “help” the CD8 response during chronic infection via IL-21-induced BATF expression.

  4. Critical role for thymic CD19+CD5+CD1dhiIL-10+ regulatory B cells in immune homeostasis.

    Science.gov (United States)

    Xing, Chen; Ma, Ning; Xiao, He; Wang, Xiaoqian; Zheng, Mingke; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Shen, Beifen; Li, Yan; Wang, Renxi

    2015-03-01

    This study tested the hypothesis that besides the spleen, LNs, peripheral blood, and thymus contain a regulatory IL-10-producing CD19(+)CD5(+)CD1d(high) B cell subset that may play a critical role in the maintenance of immune homeostasis. Indeed, this population was identified in the murine thymus, and furthermore, when cocultured with CD4(+) T cells, this population of B cells supported the maintenance of CD4(+)Foxp3(+) Tregs in vitro, in part, via the CD5-CD72 interaction. Mice homozygous for Cd19(Cre) (CD19(-/-)) express B cells with impaired signaling and humoral responses. Strikingly, CD19(-/-) mice produce fewer CD4(+)Foxp3(+) Tregs and a greater percentage of CD4(+)CD8(-) and CD4(-)CD8(+) T cells. Consistent with these results, transfer of thymic CD19(+)CD5(+)CD1d(hi) B cells into CD19(-/-) mice resulted in significantly up-regulated numbers of CD4(+)Foxp3(+) Tregs with a concomitant reduction in CD4(+)CD8(-) and CD4(-)CD8(+) T cell populations in the thymus, spleen, and LNs but not in the BM of recipient mice. In addition, thymic CD19(+)CD5(+)CD1d(hi) B cells significantly suppressed autoimmune responses in lupus-like mice via up-regulation of CD4(+)Foxp3(+) Tregs and IL-10-producing Bregs. This study suggests that thymic CD19(+)CD5(+)CD1d(hi)IL-10(+) Bregs play a critical role in the maintenance of immune homeostasis. © Society for Leukocyte Biology.

  5. The role of categorization and scale endpoint comparisons in numerical information processing: A two-process model.

    Science.gov (United States)

    Tao, Tao; Wyer, Robert S; Zheng, Yuhuang

    2017-03-01

    We propose a two-process conceptualization of numerical information processing to describe how people form impressions of a score that is described along a bounded scale. According to the model, people spontaneously categorize a score as high or low. Furthermore, they compare the numerical discrepancy between the score and the endpoint of the scale to which it is closer, if they are not confident of their categorization, and use implications of this comparison as a basis for judgment. As a result, their evaluation of the score is less extreme when the range of numbers along the scale is large (e.g., from 0 to 100) than when it is small (from 0 to 10). Six experiments support this two-process model and demonstrate its generalizability. Specifically, the magnitude of numbers composing the scale has less impact on judgments (a) when the score being evaluated is extreme, (b) when individuals are unmotivated to engage in endpoint comparison processes (i.e., they are low in need for cognition), and (c) when they are unable to do so (i.e., they are under cognitive load). Moreover, the endpoint to which individuals compare the score can depend on their regulatory focus. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  6. Numerical relativity

    International Nuclear Information System (INIS)

    Piran, T.

    1982-01-01

    There are many recent developments in numerical relativity, but there remain important unsolved theoretical and practical problems. The author reviews existing numerical approaches to solution of the exact Einstein equations. A framework for classification and comparison of different numerical schemes is presented. Recent numerical codes are compared using this framework. The discussion focuses on new developments and on currently open questions, excluding a review of numerical techniques. (Auth.)

  7. Structural and functional annotation of human FAM26F: A multifaceted protein having a critical role in the immune system.

    Science.gov (United States)

    Malik, Uzma; Javed, Aneela; Ali, Amjad; Asghar, Kashif

    2017-01-15

    Human immune system is a complex amalgam of a greatly diverse ensemble comprising of various cellular and non-cellular components, including proteins. FAM26F (family with sequence similarity 26, member F) is a relatively recently identified gene reported to play important role in diverse immune responses. Numerous studies have reported FAM26F to be differentially expressed in several viral, bacterial and parasitic infections, in certain pathophysiological conditions such as heart and liver transplantation, and in several cancers. FAM26F has also been found to be upregulated by various stimulants such as polyI:C, LPS, INF gamma and TNF alpha, and via various anticipated pathways including TLR3, TLR4 IFN-β and Dectin-1. Moreover, the synergistic expression of FAM26F on both NK-cells and myeloid dendritic cells is required to activate NK-cells against tumors via its cytoplasmic tail, thus emphasizing the therapeutic potential of FAM26F for NK sensitive tumors. Although a considerable amount of evidence is present regarding the potential role of FAM26F in immune modulation, the exact function and modulatory pathways of this gene are yet to be elucidated. We aimed to completely characterize FAM26F in order to apprehend its function and role in the immune responses. The results revealed human FAM26F to be located at chromosomal position 6q22.1. FAM26F mRNA contains 1141bp coding region encoding a 315 amino acid long, stable protein that has been well-conserved throughout evolution. It is a signal peptide deprived transmembrane protein that is secreted through non-classical pathway. The presence of a single well-conserved Ca_hom_mod domain indicated FAM26F to be a cation channel involved in the transport of molecules. A potential N-glycosylation and 14 phosphorylation sites were also predicted, along with four interacting partners of FAM26F. The secondary and tertiary structures of FAM26F were determined. Moreover, the presence of an immunoglobulin-like fold in FAM26F

  8. Nitrogen diffusion and nitrogen depth profiles in expanded austenite: experimental assessment, numerical simulation and role of stress

    DEFF Research Database (Denmark)

    Christiansen, Thomas; Dahl, Kristian Vinter; Somers, Marcel A. J.

    2008-01-01

    during gaseous nitriding, a qualitative discussion of the role of stress on local equilibrium conditions of growing expanded austenite and a discussion of the erroneous concentration dependent diffusivity of nitrogen in expanded austenite as obtained from applying the Boltzmann-Matano method...

  9. Bmi-1 plays a critical role in the protection from acute tubular necrosis by mobilizing renal stem/progenitor cells.

    Science.gov (United States)

    Lv, Xianhui; Yu, Zhenzhen; Xie, Chunfeng; Dai, Xiuliang; Li, Qing; Miao, Dengshun; Jin, Jianliang

    2017-01-22

    The regeneration of injured tubular cell occurs primarily from intrinsic renal stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal, differentiation and aging of multiple adult stem cells and progenitor cells. Bmi-1 was rapidly elevated in the induction of adult kidney regeneration by renal injury. To determine whether Bmi-1 maintained mobilization of RSCs in the protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild type (WT) and Bmi-1-deficient (Bmi-1 -/- ) mice. Their ATN phenotypes were analyzed; CD24 and CD133 double positive (CD24 + CD133 + ) cells were measured; and the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected. We found that CD24 + CD133 + RSCs were mobilized in WT ATN mice with the increased expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Critical role of SAP in progression and reactivation but not maintenance of T cell-dependent humoral immunity.

    Science.gov (United States)

    Zhong, Ming-Chao; Veillette, André

    2013-03-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is a small adaptor molecule mutated in X-linked lymphoproliferative disease, a human immunodeficiency. SAP plays a critical role in the initiation of T cell-dependent B cell responses leading to germinal center reaction, the production of high-affinity antibodies, and B cell memory. However, whether SAP has a role in these responses beyond their initiation is not known. It is important to address this matter not only for mechanistic reasons but also because blockade of the SAP pathway is being contemplated as a means to treat autoimmune diseases in humans. Using an inducibly SAP deficient mouse, we found that SAP was required not only for the initiation but also for the progression of primary T cell-driven B cell responses to haptens. It was also necessary for the reactivation of T cell-dependent B cell immunity during secondary immune responses. These activities consistently correlated with the requirement of SAP for full expression of the lineage commitment factor Bcl-6 in follicular T helper (T(FH)) cells. However, once memory B cells and long-lived antibody-secreting cells were established, SAP became dispensable for maintaining T cell-dependent B cell responses. Thus, SAP is pivotal for nearly all phases, but not for maintenance, of T cell-driven B cell humoral immunity. These findings may have implications for the treatment of immune disorders by targeting the SAP pathway.

  11. Updating appetitive memory during reconsolidation window: critical role of cue-directed behavior and amygdala central nucleus.

    Science.gov (United States)

    Olshavsky, Megan E; Song, Bryan J; Powell, Daniel J; Jones, Carolyn E; Monfils, Marie-H; Lee, Hongjoo J

    2013-01-01

    When presented with a light cue followed by food, some rats simply approach the foodcup (Nonorienters), while others first orient to the light in addition to displaying the food-cup approach behavior (Orienters). Cue-directed orienting may reflect enhanced attentional and/or emotional processing of the cue, suggesting divergent natures of cue-information processing in Orienters and Nonorienters. The current studies investigate how differences in cue processing might manifest in appetitive memory retrieval and updating using a paradigm developed to persistently attenuate fear responses (Retrieval-extinction paradigm; Monfils et al., 2009). First, we examined whether the retrieval-extinction paradigm could attenuate appetitive responses in Orienters and Nonorienters. Next, we investigated if the appetitive memory could be updated using reversal learning (fear conditioning) during the reconsolidation window (as opposed to repeated unreinforced trials, i.e., extinction). Both extinction and new fear learning given within the reconsolidation window were effective at persistently updating the initial appetitive memory in the Orienters, but not the Nonorienters. Since conditioned orienting is mediated by the amygdala central nucleus (CeA), our final experiment examined the CeA's role in the retrieval-extinction process. Bilateral CeA lesions interfered with the retrieval-extinction paradigm-did not prevent spontaneous recovery of food-cup approach. Together, our studies demonstrate the critical role of conditioned orienting behavior and the CeA in updating appetitive memory during the reconsolidation window.

  12. Bmi-1 plays a critical role in the protection from acute tubular necrosis by mobilizing renal stem/progenitor cells

    International Nuclear Information System (INIS)

    Lv, Xianhui; Yu, Zhenzhen; Xie, Chunfeng; Dai, Xiuliang; Li, Qing; Miao, Dengshun; Jin, Jianliang

    2017-01-01

    The regeneration of injured tubular cell occurs primarily from intrinsic renal stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal, differentiation and aging of multiple adult stem cells and progenitor cells. Bmi-1 was rapidly elevated in the induction of adult kidney regeneration by renal injury. To determine whether Bmi-1 maintained mobilization of RSCs in the protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild type (WT) and Bmi-1-deficient (Bmi-1 −/− ) mice. Their ATN phenotypes were analyzed; CD24 and CD133 double positive (CD24 + CD133 + ) cells were measured; and the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected. We found that CD24 + CD133 + RSCs were mobilized in WT ATN mice with the increased expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN.

  13. The critical role of nurses to the successful implementation of the National Safety and Quality Health Service Standards.

    Science.gov (United States)

    Twigg, Diane E; Duffield, Christine; Evans, Gemma

    2013-09-01

    The National Safety and Quality Health Service Standards requires health service compliance by 2013 and covers several areas including governance arrangements, partnerships with consumers and eight key clinical processes. Nurses in Australia comprise 62% of the hospital workforce, are the largest component and hence play a critical role in meeting these standards and improving the quality of patient care. Several of the standards are influenced by nursing interventions, which incorporate any direct-care treatment that the nurse performs for a patient that may be nurse or physician initiated. The ability for nurses to undertake these interventions is influenced by the hours of care available, the skill mix of the nursing workforce and the environment in which they practice. Taking into consideration the predicted nursing shortages, the challenge to successfully implement the National Safety and Quality Health Service Standards will be great. This paper examines the role of nursing in the delivery of the National Standards, analyses the evidence with regard to nursing-sensitive outcomes and discusses the implications for health service decision makers and policy.

  14. Numerical Analysis of S-CO{sub 2} Test Loop Transient Conditions near the Critical Point of CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Seong Jun; Oh, Bongseong; Ahn, Yoonhan; Baik, Seongjoon; Lee, Jekyoung; Lee, Jeong Ik [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    It was identified that controlling CO{sub 2} compressor operation near the critical point is one of the most important issues to operate a S-CO{sub 2} Brayton cycle with a high efficiency. Despite the growing interest in the S-CO{sub 2} Brayton cycle, a few previous research on the transient analysis of the S-CO{sub 2} system has been conducted previously. Moreover, previous studies have some limitation in the modelled test facility, and the experiment was not performed to observe specific scenario. The KAIST research team has conducted S-CO{sub 2} system transient experiments with the CO{sub 2} compressing test facility called SCO{sub 2}PE (Supercritical CO{sub 2} Pressurizing Experiment) at KAIST In this study, authors use the transient analysis code GAMMA (Gas Multidimensional Multicomponent mixture Analysis) code for analyzing the experiment. Two transient scenarios were selected in this study; over cooling and under cooling situations. The selected transient situation is of particular interest since the compressor inlet conditions start to drift away from the critical point of CO{sub 2}. The results represent that the GAMMA code can simulate the S-CO{sub 2} test facility, SCO{sub 2}PE. However, as shown in the cooling water flow rate increasing scenario, the GAMMA code shows calculation error when the phase change occurs. Furthermore, although the results of the cooling water flow rate decrease case shows reasonable agreement with the experimental data, there are still some unexplained differences between the experimental data and the GAMMA code prediction.

  15. The Ror1 receptor tyrosine kinase plays a critical role in regulating satellite cell proliferation during regeneration of injured muscle.

    Science.gov (United States)

    Kamizaki, Koki; Doi, Ryosuke; Hayashi, Makoto; Saji, Takeshi; Kanagawa, Motoi; Toda, Tatsushi; Fukada, So-Ichiro; Ho, Hsin-Yi Henry; Greenberg, Michael Eldon; Endo, Mitsuharu; Minami, Yasuhiro

    2017-09-22

    The Ror family receptor tyrosine kinases, Ror1 and Ror2, play important roles in regulating developmental morphogenesis and tissue- and organogenesis, but their roles in tissue regeneration in adult animals remain largely unknown. In this study, we examined the expression and function of Ror1 and Ror2 during skeletal muscle regeneration. Using an in vivo skeletal muscle injury model, we show that expression of Ror1 and Ror2 in skeletal muscles is induced transiently by the inflammatory cytokines, TNF-α and IL-1β, after injury and that inhibition of TNF-α and IL-1β by neutralizing antibodies suppresses expression of Ror1 and Ror2 in injured muscles. Importantly, expression of Ror1 , but not Ror2 , was induced primarily in Pax7-positive satellite cells (SCs) after muscle injury, and administration of neutralizing antibodies decreased the proportion of Pax7-positive proliferative SCs after muscle injury. We also found that stimulation of a mouse myogenic cell line, C2C12 cells, with TNF-α or IL-1β induced expression of Ror1 via NF-κB activation and that suppressed expression of Ror1 inhibited their proliferative responses in SCs. Intriguingly, SC-specific depletion of Ror1 decreased the number of Pax7-positive SCs after muscle injury. Collectively, these findings indicate for the first time that Ror1 has a critical role in regulating SC proliferation during skeletal muscle regeneration. We conclude that Ror1 might be a suitable target in the development of diagnostic and therapeutic approaches to manage muscular disorders. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Experimental and numerical analysis of stress wave propagation in polymers and the role of interfaces in armour systems

    Science.gov (United States)

    Gorwade, Chandragupt V.; Ashcroft, Ian A.; Silberschmidt, Vadim V.; Hughes, Foz T. R.; Swallowe, Gerry M.

    2012-12-01

    Advanced polymeric materials are finding an increasing range of industrial and defence applications. These materials have the potential to improve combat survivability, whilst reducing the cost and weight of armour systems. In this paper the results from a split Hopkinson pressure bar (SHPB) test of a high density polyethylene (HDPE) sample involving multiple stress waves is discussed with aid of a finite element model of the test. It is seen that the phenomenon of impedance mismatch at interfaces plays an important role in the levels of stress and deformation seen in the sample. A multi-layer armour system is then investigated using the finite element model. This case study illustrates the role of impedance mismatch and interface engineering in the design and optimisation of armour solutions.

  17. Numerical investigations on the effect of the axial interval between intensifying spacer grids on the critical heat flux value for fuel assemblies with non-uniform axial power distribution

    International Nuclear Information System (INIS)

    Kireeva, D.; Oleksyuk, D.

    2015-01-01

    In this paper a number of numerical studies on intensifying heat exchange conducted by NRC 'Kurchatov Institute' are presented. A standardised heat exchange intensifying spacer grid (UDRI) can be installed at any height along the fuel assembly (FA) heat-generating section. When installed at the bottom of a fuel assembly, the UDRI facilitates intensive coolant mixing; the UDRI mounted at the top of a FA provides better mixing and the enhancement in heat exchange. The application of the heat exchange intensifying spacer grids results in better flattening of the coolant parameters along the cross-section and higher critical heat flux ratio. The investigations were carried out by means of numerical code SC-INT using mesh generation that have been specially designed by NRC 'Kurchatov Institute' to perform calculations for fuel assemblies equipped with the intensifying spacer grids. The effect of the axial interval between UDRI grids on the critical heat flux value for two typical axial power shapes has been investigated. The derived optimal solutions for the positioning of intensifying grids are also presented

  18. Numerical analysis of breakdown dynamics dependence on pulse width in laser-induced damage in fused silica: Role of optical system

    Science.gov (United States)

    Hamam, Kholoud A.; Gamal, Yosr E. E.-D.

    2018-06-01

    We report a numerical investigation of the breakdown and damage in fused silica caused by ultra-short laser pulses. The study based on a modified model (Gaabour et al., 2012) that solves the rate equation numerically for the electron density evolution during the laser pulse, under the combined effect of both multiphoton and electron impact ionization processes. Besides, electron loss processes due to diffusion out of the focal volume and recombination are also considered in this analysis. The model is applied to investigate the threshold intensity dependence on laser pulse width in the experimental measurements that are given by Liu et al. (2005). In this experiment, a Ti-sapphire laser source operating at 800 nm with pulse duration varies between 240 fs and 2.5 ps is used to irradiate a bulk of fused silica with dimensions 10 × 5 × 3 mm. The laser beam was focused into the bulk using two optical systems with effective numerical apertures (NA) 0.126 and 0.255 to give beam spot radius at the focus of the order 2.0 μm and 0.95 μm respectively. Reasonable agreement between the calculated thresholds and the measured ones is attained. Moreover, a study is performed to examine the respective role of the physical processes of the breakdown of fused silica in relation to the pulse width and focusing optical system. The analysis revealed a real picture of the location and size of the generated plasma.

  19. Slc39a7/zip7 plays a critical role in development and zinc homeostasis in zebrafish.

    Directory of Open Access Journals (Sweden)

    Guang Yan

    Full Text Available BACKGROUND: Slc39a7/Zip7, also known as Ke4, is a member of solute carrier family 39 (Slc39a and plays a critical role in regulating cell growth and death. Because the function of Zip7 in vivo was unclear, the present study investigated the function of zip7 in vertebrate development and zinc metabolism using zebrafish as a model organism. PRINCIPAL FINDING: Using real-time PCR to determine the gene expression pattern of zip7 during zebrafish development, we found that zip7 mRNA is expressed throughout embryonic development and into maturity. Interestingly, whole mount in situ hybridization revealed that while zip7 mRNA is ubiquitously expressed until 12 hours post-fertilization (hpf; at 24 hpf and beyond, zip7 mRNA was specifically detected only in eyes. Morpholino-antisense (MO gene knockdown assay revealed that downregulation of zip7 expression resulted in several morphological defects in zebrafish including decreased head size, smaller eyes, shorter palates, and shorter and curved spinal cords. Analysis by synchrotron radiation X-ray fluorescence (SR-XRF showed reduced concentrations of zinc in brain, eyes, and gills of zip7-MO-injected embryos. Furthermore, incubation of the zip7 knockdown embryos in a zinc-supplemented solution was able to rescue the MO-induced morphological defects. SIGNIFICANCE: Our data suggest that zip7 is required for eye, brain, and skeleton formation during early embryonic development in zebrafish. Moreover, zinc supplementation can partially rescue defects resulting from zip7 gene knockdown. Taken together, our data provide critical insight into a novel function of zip7 in development and zinc homeostasis in vivo in zebrafish.

  20. The critical role of the industrial sector in reaching long-term emission reduction, energy efficiency and renewable targets

    International Nuclear Information System (INIS)

    Fais, Birgit; Sabio, Nagore; Strachan, Neil

    2016-01-01

    Highlights: • A new industrial modelling approach in a whole energy systems model is developed. • The contribution of UK industry to long-term energy policy targets is analysed. • Emission reductions of up to 77% can be achieved in the UK industry until 2050. • The UK industry sector is essential for achieving the overall efficiency commitments. • UK industry can make a moderate contribution to the expansion of renewable energies. - Abstract: This paper evaluates the critical contribution of the industry sector to long-term decarbonisation, efficiency and renewable energy policy targets. Its methodological novelty is the incorporation of a process-oriented modelling approach based on a comprehensive technology database for the industry sector in a national energy system model for the UK (UKTM), allowing quantification of the role of both decarbonisation of upstream energy vectors and of mitigation options in the industrial sub-categories. This enhanced model is then applied in a comparative policy scenario analysis that explores various target dimensions on emission mitigation, renewable energy and energy efficiency at both a national and European level. The results show that ambitious emission cuts in the industry sector of up to 77% until 2050 compared to 2010 can be achieved. Moreover, with a reduction in industrial energy demand of up to 31% between 2010 and 2050, the sector is essential for achieving the overall efficiency commitments. The industry sector also makes a moderate contribution to the expansion of renewable energies mostly through the use of biomass for low-temperature heating services. However, additional sub-targets on renewable sources and energy efficiency need to be assessed critically, as they can significantly distort the cost-efficiency of the long-term mitigation pathway.

  1. The Hinge Segment of Human NADPH-Cytochrome P450 Reductase in Conformational Switching: The Critical Role of Ionic Strength

    Directory of Open Access Journals (Sweden)

    Diana Campelo

    2017-10-01

    Full Text Available NADPH-cytochrome P450 reductase (CPR is a redox partner of microsomal cytochromes P450 and is a prototype of the diflavin reductase family. CPR contains 3 distinct functional domains: a FMN-binding domain (acceptor reduction, a linker (hinge, and a connecting/FAD domain (NADPH oxidation. It has been demonstrated that the mechanism of CPR exhibits an important step in which it switches from a compact, closed conformation (locked state to an ensemble of open conformations (unlocked state, the latter enabling electron transfer to redox partners. The conformational equilibrium between the locked and unlocked states has been shown to be highly dependent on ionic strength, reinforcing the hypothesis of the presence of critical salt interactions at the interface between the FMN and connecting FAD domains. Here we show that specific residues of the hinge segment are important in the control of the conformational equilibrium of CPR. We constructed six single mutants and two double mutants of the human CPR, targeting residues G240, S243, I245 and R246 of the hinge segment, with the aim of modifying the flexibility or the potential ionic interactions of the hinge segment. We measured the reduction of cytochrome c at various salt concentrations of these 8 mutants, either in the soluble or membrane-bound form of human CPR. All mutants were found capable of reducing cytochrome c yet with different efficiency and their maximal rates of cytochrome c reduction were shifted to lower salt concentration. In particular, residue R246 seems to play a key role in a salt bridge network present at the interface of the hinge and the connecting domain. Interestingly, the effects of mutations, although similar, demonstrated specific differences when present in the soluble or membrane-bound context. Our results demonstrate that the electrostatic and flexibility properties of the hinge segment are critical for electron transfer from CPR to its redox partners.

  2. Guided-inquiry based laboratory instruction: Investigation of critical thinking skills, problem solving skills, and implementing student roles in chemistry

    Science.gov (United States)

    Gupta, Tanya

    Recent initiatives in the laboratory curriculum have encouraged an inquiry-based approach to learning and teaching in the laboratory. It has been argued that laboratory instruction should not just be hands-on, but it should portray the essence of inquiry through the process of experiential learning and reflective engagement in collaboration with peers and in facilitation by the instructor. A student-centered active learning approach may be an effective way to enhance student understanding of concepts in the laboratory. The dissertation research work explores the impact of laboratory instruction and its relevance for college-level chemistry. Each chapter is different from the preceding chapter in terms of the purpose of the study and the research questions asked. However, the overarching idea is to address the importance of guided-inquiry based laboratory instruction in chemistry and its relevance in helping students to make connections with the chemistry content and in imparting skills to students. Such skills include problem solving, collaborative group work and critical thinking. The first research study (Chapter 2) concerns the impact of first year co-requisite general chemistry laboratory instruction on the problem-solving skills of students. The second research study (Chapter 3) examines the impact of implementing student roles also known as Student-Led Instructor Facilitated Guided-Inquiry based Laboratories, SLIFGIL) by modifying the Science Writing Heuristic approach of laboratory instruction. In the third research study (Chapter 4), critical thinking skills of first semester general chemistry laboratory students were compared to advanced (third or fourth year) chemistry laboratory students based on the analysis of their laboratory reports.

  3. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    Energy Technology Data Exchange (ETDEWEB)

    Doi, Keiko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute of Life Sciences for the Next Generation of Women Scientists, Fukuoka University, Fukuoka (Japan); Fujimoto, Takahiro [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Okamura, Tadashi [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ogawa, Masahiro [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tanaka, Yoko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Mototani, Yasumasa; Goto, Motohito [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ota, Takeharu; Matsuzaki, Hiroshi [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Kuroki, Masahide [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tsunoda, Toshiyuki [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Sasazuki, Takehiko [Institute for Advanced Study, Kyushu University, Fukuoka (Japan); Shirasawa, Senji, E-mail: sshirasa@fukuoka-u.ac.jp [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. Black-Right-Pointing-Pointer Zfat-deficiency leads to reduction in the number of the peripheral T cells. Black-Right-Pointing-Pointer Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Decreased expression of IL-7R{alpha}, IL-2R{alpha} and IL-2 in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7R{alpha} and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2R{alpha} expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  4. Structural Snapshots of an Engineered Cystathionine-γ-lyase Reveal the Critical Role of Electrostatic Interactions in the Active Site

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Wupeng; Stone, Everett; Zhang, Yan Jessie

    2017-02-01

    Enzyme therapeutics that can degrade l-methionine (l-Met) are of great interest as numerous malignancies are exquisitely sensitive to l-Met depletion. To exhaust the pool of methionine in human serum, we previously engineered an l-Met-degrading enzyme based on the human cystathionine-γ-lyase scaffold (hCGL-NLV) to circumvent immunogenicity and stability issues observed in the preclinical application of bacterially derived methionine-γ-lyases. To gain further insights into the structure–activity relationships governing the chemistry of the hCGL-NLV lead molecule, we undertook a biophysical characterization campaign that captured crystal structures (2.2 Å) of hCGL-NLV with distinct reaction intermediates, including internal aldimine, substrate-bound, gem-diamine, and external aldimine forms. Curiously, an alternate form of hCGL-NLV that crystallized under higher-salt conditions revealed a locally unfolded active site, correlating with inhibition of activity as a function of ionic strength. Subsequent mutational and kinetic experiments pinpointed that a salt bridge between the phosphate of the essential cofactor pyridoxal 5'-phosphate (PLP) and residue R62 plays an important role in catalyzing β- and γ-eliminations. Our study suggests that solvent ions such as NaCl disrupt electrostatic interactions between R62 and PLP, decreasing catalytic efficiency.

  5. The critical role of community-based micro-grants for disability aids and equipment: results from a needs analysis.

    Science.gov (United States)

    Muenchberger, Heidi; Ehrlich, Carolyn; Parekh, Sanjoti; Crozier, Michelle

    2016-01-01

    To investigate the role of philanthropic micro-grants (maximum of $10,000) in the provision of aids and equipment for adults (aged 18-65 years of age) with complex disabilities and examine key trends in aids and equipment requests. This study examined, through quantitative and qualitative analysis, aids and equipment requests (n = 371 individual applications as represented by 136 service organisations in three Australian states) received by a not-for-profit (NFP) organisation across five consecutive years of an innovative micro-grants scheme. Findings highlight that living situation (living with family or living independently) significantly influences the nature of requests for respite, aids, equipment and home modifications. Specifically, people with complex disabilities living with their families require greater combined service provision (higher equipment need, respite support, home modifications) than those living independently (equipment need only). Type of disability did not influence request type. Qualitative data further indicated the "last resort" nature of respite requests, particularly for younger applicants (under 45 years of age) indicating critical unmet needs in the community. Results demonstrate the vital role of NFP organisations and philanthropic funds in supporting daily lifestyle aids and equipment (including respite) that might otherwise not be funded for people with complex disabilities. Although preliminary in its scope and prior to implementation of a National Disability Insurance Scheme (NDIS) in Australia, findings suggest both opportunity and risk to the uptake of community-based micro-grant funding: opportunity for users through the provision of essential aids and lifestyle supports, and risk through over-subscription and devolving of responsibility for critical support resources from public sector. The aids and equipment needs of adults under the age of 65 appear to have been underestimated, poorly defined and under

  6. Vasculogenic Mimicry of HT1080 Tumour Cells In Vivo: Critical Role of HIF-1α-Neuropilin-1 Axis

    Science.gov (United States)

    Misra, Roli M.; Bajaj, Manmohan S.; Kale, Vaijayanti P.

    2012-01-01

    HT1080 - a human fibrosarcoma-derived cell line – forms aggressive angiogenic tumours in immuno-compromised mice. In spite of its extensive use as a model of tumour angiogenesis, the molecular event(s) initiating the angiogenic program in these cells are not known. Since hypoxia stimulates tumour angiogenesis, we examined the hypoxia-induced events evoked in these cells. In contrast to cells grown under normoxic conditions, hypoxia-primed (1% O2) HT1080 cells formed robust tubules on growth factor-reduced matrigel and formed significantly larger tumours in xenograft models in a chetomin-sensitive manner, indicating the role of HIF-1α-mediated transcription in these processes. Immuno-histochemical analyses of tumours formed by GFP-expressing HT1080 cells clearly showed that the tumour cells themselves expressed various angiogenic markers including Neuropilin-1 (NRP-1) and formed functional vessels containing red blood cells, thereby unambiguously demonstrating the vasculogenic mimicry of HT1080 cells in vivo. Experiments performed with the HT1080 cells stably transfected with plasmid constructs expressing shNRP-1 or full-length NRP-1 clearly established that the HIF1α-mediated up-regulation of NRP-1 played a deterministic role in the process. Hypoxia-exposure resulted in an up-regulation of c-Myc and OCT3/4 and a down-regulation of KLF4 mRNAs, suggesting their involvement in the tumour formation and angiogenesis. However, silencing of NRP-1 alone, though not affecting proliferation in culture, was sufficient to abrogate the tumour formation completely; clearly establishing that the hypoxia-mediated HIF-1α-dependent up-regulation of NRP-1 is a critical molecular event involved in the vasculogenic mimicry and tumor formation by HT1080 cells in vivo. PMID:23185562

  7. A Critical Role for CD200R Signaling in Limiting the Growth and Metastasis of CD200+ Melanoma.

    Science.gov (United States)

    Liu, Jin-Qing; Talebian, Fatemeh; Wu, Lisha; Liu, Zhihao; Li, Ming-Song; Wu, Laichu; Zhu, Jianmin; Markowitz, Joseph; Carson, William E; Basu, Sujit; Bai, Xue-Feng

    2016-08-15

    CD200 is a cell surface glycoprotein that functions through engaging CD200R on cells of the myeloid lineage and inhibits their functions. Expression of CD200 was implicated in a variety of human cancer cells, including melanoma cells; however, its roles in tumor growth and immunity are not clearly understood. In this study, we used CD200R-deficient mice and the B16 tumor model to evaluate this issue. We found that CD200R-deficient mice exhibited accelerated growth of CD200(+), but not CD200(-), B16 tumors. Strikingly, CD200R-deficient mice receiving CD200(+) B16 cells i.v. exhibited massive tumor growth in multiple organs, including liver, lung, kidney, and peritoneal cavity, whereas the growth of the same tumors in wild-type mice was limited. CD200(+) tumors grown in CD200R-deficient mice contained higher numbers of CD11b(+)Ly6C(+) myeloid cells, exhibited increased expression of VEGF and HIF1α genes with increased angiogenesis, and showed significantly reduced infiltration of CD4(+) and CD8(+) T cells, presumably as the result of reduced expression of T cell chemokines, such as CXCL9 and CXCL16. The liver from CD200R-deficient mice, under metastatic growth of CD200(+) tumors, contained significantly increased numbers of CD11b(+)Gr1(-) myeloid cells and Foxp3(+) regulatory T cells and reduced numbers of NK cells. Liver T cells also had a reduced capacity to produce IFN-γ or TNF-α. Taken together, we revealed a critical role for CD200R signaling in limiting the growth and metastasis of CD200(+) tumors. Thus, targeting CD200R signaling may potentially interfere with the metastatic growth of CD200(+) tumors, like melanoma. Copyright © 2016 by The American Association of Immunologists, Inc.

  8. Numerical analysis

    CERN Document Server

    Khabaza, I M

    1960-01-01

    Numerical Analysis is an elementary introduction to numerical analysis, its applications, limitations, and pitfalls. Methods suitable for digital computers are emphasized, but some desk computations are also described. Topics covered range from the use of digital computers in numerical work to errors in computations using desk machines, finite difference methods, and numerical solution of ordinary differential equations. This book is comprised of eight chapters and begins with an overview of the importance of digital computers in numerical analysis, followed by a discussion on errors in comput

  9. Numerical relativity

    CERN Document Server

    Shibata, Masaru

    2016-01-01

    This book is composed of two parts: First part describes basics in numerical relativity, that is, the formulations and methods for a solution of Einstein's equation and general relativistic matter field equations. This part will be helpful for beginners of numerical relativity who would like to understand the content of numerical relativity and its background. The second part focuses on the application of numerical relativity. A wide variety of scientific numerical results are introduced focusing in particular on the merger of binary neutron stars and black holes.

  10. A comparison of debate and role play in enhancing critical thinking and communication skills of medical students during problem based learning.

    Science.gov (United States)

    Latif, Rabia; Mumtaz, Sadaf; Mumtaz, Rafia; Hussain, Aamir

    2018-04-18

    Debate and role play for learning critical thinking and communication skills are being increasingly used in various undergraduate medical schools worldwide. We aim to compare students' views about effectiveness of two teaching strategies; debate and role play to exercise critical thinking and communication skills during problem-based learning (PBL). This is a comparative, cross-sectional, and questionnaire-based study. Our subjects were second year undergraduate female medical students enrolled in Imam Abdulrahman Bin Faisal University (IAU), College of Medicine from September 2014-2016, divided into 10 small PBL groups (10-13 students/group/year). Students rated role play and debate as equally effective in improving communication skills. Debate was rated superior to role play in "opening new avenues of thinking" (p-value is 0.01), whereas in "integration of knowledge of basic medical sciences with clinical skills" and "reflection of real life experience" students rated role play being superior to debate (p-value 0.01 and 0.00, respectively). Both role play and debate are well accepted by the students in PBL curriculum as an effective teaching methodology. Both are perceived equally good in improving students' communication skills. Few aspects of critical thinking are improved more by role plays compared to debate and vice versa. © 2018 by The International Union of Biochemistry and Molecular Biology, 2018. © 2018 The International Union of Biochemistry and Molecular Biology.

  11. 'Not good enough:' Exploring self-criticism's role as a mediator between childhood emotional abuse & adult binge eating.

    Science.gov (United States)

    Feinson, Marjorie C; Hornik-Lurie, Tzipi

    2016-12-01

    Empirical studies have identified emotional abuse in childhood (CEA) as a risk factor with long-term implications for psychological problems. Indeed, recent studies indicate it is more prevalent than behavioral forms of abuse, (i.e. childhood sexual and physical abuse) and the childhood trauma most clearly associated with subsequent eating pathology in adulthood. However, relatively little is understood about the mechanisms linking these distal experiences. This study explores three psychological mechanisms - self-criticism (SC), depression and anxiety symptoms - as plausible mediators that may account for the relationship between CEA and binge eating (BE) among adult women. Detailed telephone interviews conducted with a community-based sample of 498 adult women (mean age 44) assess BE, CEA and SC along with the most frequently researched psychological variables, anxiety and depression. Regression analyses reveal that BE is partially explained by CEA along with the three mediators. Bootstrapping analysis, which compares multiple mediators within a single model using thousands of repeated random sampling observations from the data set, reveals a striking finding: SC is the only psychological variable that makes a significant contribution to explaining BE severity. The unique role of punitive self-evaluations vis-à-vis binge eating warrants additional research and, in the interim, that clinicians consider broadening treatment interventions accordingly. Copyright © 2016. Published by Elsevier Ltd.

  12. Frank A. Beach award: programming of neuroendocrine function by early-life experience: a critical role for the immune system.

    Science.gov (United States)

    Bilbo, Staci D

    2013-05-01

    Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system, and several have a striking etiology in development as well. Our recent evidence using a rodent model of neonatal Escherichia coli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood, and suggests that the early-life immune history of an individual may be critical to understanding the relative risk of developing later-life mental health disorders in humans. A single neonatal infection programs the function of immune cells within the brain, called microglia, for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits. I describe the important role of the immune system, notably microglia, during brain development, and discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, and cognition. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Success rates in smoking cessation: Psychological preparation plays a critical role and interacts with other factors such as psychoactive substances.

    Science.gov (United States)

    Joly, Bertrand; Perriot, Jean; d'Athis, Philippe; Chazard, Emmanuel; Brousse, Georges; Quantin, Catherine

    2017-01-01

    The aim of this study was to identify factors associated with the results of smoking cessation attempts. Data were collected in Clermont-Ferrand from a smoking cessation clinic between 1999 and 2009 (1,361 patients). Smoking cessation was considered a success when patients were abstinent 6 months after the beginning of cessation. Multivariate logistic regression was used to investigate the association between abstinence and different factors. The significant factors were a history of depression (ORadjusted = 0.57, p = 0.003), state of depression at the initial consultation (ORa = 0.64, p = 0.005), other psychoactive substances (ORa = 0.52, psuccess was four times higher). A high score in the Richmond test had a greater impact on success with increasing age (significant interaction: p = 0.01). In exclusive smokers, the contemplation level in the Prochaska algorithm was enough to obtain a satisfactory abstinence rate (65.5%) whereas among consumers of other psychoactive substances, it was necessary to reach the preparation level in the Prochaska algorithm to achieve a success rate greater than 50% (significant interaction: p = 0.02). The psychological preparation of the smoker plays a critical role. The management of smoking cessation must be personalized, especially for consumers of other psychoactive substances and/or smokers with a history of depression.

  14. Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection.

    Directory of Open Access Journals (Sweden)

    Amanda C Stanley

    2011-10-01

    Full Text Available LIGHT (TNFSF14 is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM and lymphotoxin-beta receptor (LTβR. We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNγ- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTβR interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4(+ T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage.

  15. Role of Theories in the Design of Web-Based Person-Centered Support: A Critical Analysis

    Directory of Open Access Journals (Sweden)

    Agneta Ranerup

    2014-01-01

    Full Text Available Objective. The aim of this study was to provide a critical understanding of the role of theories and their compatibility with a person-centered approach in the design and evaluation of web-based support for the management of chronic illness. Methods. Exploration of web-based support research projects focusing on four cases: (1 preschool children aged 4–6 with bladder dysfunction and urogenital malformation; (2 young adults aged 16–25 living with mental illness; (3 women with type 1 diabetes who are pregnant or in early motherhood; and (4 women who have undergone surgery for breast cancer. Data comprised interviews with research leaders and documented plans. Analysis was performed by means of a cross-case methodology. Results. The used theories concerned design, learning, health and well-being, or transition. All web support products had been developed using a participatory design (PD. Fundamental to the technology design and evaluation of outcomes were theories focusing on learning and on health and well-being. All theories were compatible with a person-centered approach. However, a notable exception was the relatively collective character of PD and Communities of Practice. Conclusion. Our results illustrate multifaceted ways for theories to be used in the design and evaluation of web-based support.

  16. Critical care medicine as a distinct product line with substantial financial profitability: the role of business planning.

    Science.gov (United States)

    Bekes, Carolyn E; Dellinger, R Phillip; Brooks, Daniel; Edmondson, Robert; Olivia, Christopher T; Parrillo, Joseph E

    2004-05-01

    As academic health centers face increasing financial pressures, they have adopted a more businesslike approach to planning, particularly for discrete "product" or clinical service lines. Since critical care typically has been viewed as a service provided by a hospital, and not a product line, business plans have not historically been developed to expand and promote critical care. The major focus when examining the finances of critical care has been cost reduction, not business development. We hypothesized that a critical care business plan can be developed and analyzed like other more typical product lines and that such a critical care product line can be profitable for an institution. In-depth analysis of critical care including business planning for critical care services. Regional academic health center in southern New Jersey. None. As part of an overall business planning process directed by the Board of Trustees, the critical care product line was identified by isolating revenue, expenses, and profitability associated with critical care patients. We were able to identify the major sources ("value chain") of critical care patients: the emergency room, patients who are admitted for other problems but spend time in a critical care unit, and patients transferred to our intensive care units from other hospitals. The greatest opportunity to expand the product line comes from increasing the referrals from other hospitals. A methodology was developed to identify the revenue and expenses associated with critical care, based on the analysis of past experience. With this model, we were able to demonstrate a positive contribution margin of dollar 7 million per year related to patients transferred to the institution primarily for critical care services. This can be seen as the profit related to the product line segment of critical care. There was an additional positive contribution margin of dollar 5.8 million attributed to the critical care portion of the hospital stay of

  17. RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

    Directory of Open Access Journals (Sweden)

    Elias Abdou

    2017-05-01

    Full Text Available For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original “in vitro model of persistence” consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ΔregA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12% of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL, were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work

  18. Numerical analysis of breakdown dynamics dependence on pulse width in laser-induced damage in fused silica: Role of optical system

    Directory of Open Access Journals (Sweden)

    Kholoud A. Hamam

    2018-06-01

    Full Text Available We report a numerical investigation of the breakdown and damage in fused silica caused by ultra-short laser pulses. The study based on a modified model (Gaabour et al., 2012 that solves the rate equation numerically for the electron density evolution during the laser pulse, under the combined effect of both multiphoton and electron impact ionization processes. Besides, electron loss processes due to diffusion out of the focal volume and recombination are also considered in this analysis. The model is applied to investigate the threshold intensity dependence on laser pulse width in the experimental measurements that are given by Liu et al. (2005. In this experiment, a Ti-sapphire laser source operating at 800 nm with pulse duration varies between 240 fs and 2.5 ps is used to irradiate a bulk of fused silica with dimensions 10 × 5 × 3 mm. The laser beam was focused into the bulk using two optical systems with effective numerical apertures (NA 0.126 and 0.255 to give beam spot radius at the focus of the order 2.0 μm and 0.95 μm respectively. Reasonable agreement between the calculated thresholds and the measured ones is attained. Moreover, a study is performed to examine the respective role of the physical processes of the breakdown of fused silica in relation to the pulse width and focusing optical system. The analysis revealed a real picture of the location and size of the generated plasma. Keywords: Ultra-short laser pulses, Ablation mechanisms, Electron density, Electron loss processes, Avalanche ionization, Breakdown threshold

  19. Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the endocrine system and social behaviours.

    Science.gov (United States)

    Masugi-Tokita, M; Yoshida, T; Kageyama, S; Kawata, M; Kawauchi, A

    2018-03-01

    Metabotropic glutamate receptor subtype 7 (mGluR7) is one of the group III mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and localised to presynaptic active zones of the mammalian central nervous system. We previously reported that mGluR7 is essential for intermale aggression and amygdala-dependent fear learning. To elucidate the role of mGluR7 in the neuroendocrine system, we performed biochemical analyses and found a significant reduction of testosterone levels in mGluR7 knockout (KO) mice. Testosterone replacement restored intermale aggressive behaviour in castrated wild-type mice to the level of gonadally intact wild-type mice. However, given the same dosage of testosterone replacement, mGluR7 KO mice showed almost no aggressive behaviour. These results indicate that reduction of plasma testosterone is unrelated to the deficit in intermale aggression in mGluR7 KO mice. Social investigating behaviour of intact mGluR7 KO mice also differed from that of wild-type mice; e.g. the KO mice showing less frequent anogenital sniffing and more frequent grooming behaviour. Testosterone replacement increased anogenital sniffing and grooming behaviour in castrated mGluR7 KO mice, while the differences were still present between castrated wild-type mice and KO mice after both underwent testosterone replacement. These results imply that reduction of plasma testosterone may partially inhibit social investigating behaviours in intact mGluR7 KO mice. Furthermore, castrated mGluR7 KO mice have smaller seminal vesicles than those of castrated wild-type mice, although seminal vesicle weights were normal in intact mice. These observations suggest that, besides testicular testosterone, some other hormone levels may be dysregulated in mGluR7 KO mice, and indicate a critical role of mGluR7 in the endocrine system. Taken together, our findings demonstrate that mGluR7 is essential for the regulation of the endocrine system, in addition to innate behaviours

  20. Critical role of heat shock protein 27 in bufalin-induced apoptosis in human osteosarcomas: a proteomic-based research.

    Directory of Open Access Journals (Sweden)

    Xian-biao Xie

    Full Text Available Bufalin is the primary component of the traditional Chinese herb "Chan Su". Evidence suggests that this compound possesses potent anti-tumor activities, although the exact molecular mechanism(s is unknown. Our previous study showed that bufalin inhibited growth of human osteosarcoma cell lines U2OS and U2OS/MTX300 in culture. Therefore, this study aims to further clarify the in vitro and in vivo anti-osteosarcoma effects of bufalin and its molecular mechanism of action. We found bufalin inhibited both methotrexate (MTX sensitive and resistant human osteosarcoma cell growth and induced G2/M arrest and apoptosis. Using a comparative proteomics approach, 24 differentially expressed proteins following bufalin treatment were identified. In particular, the level of an anti-apoptotic protein, heat shock protein 27 (Hsp27, decreased remarkably. The down-regulation of Hsp27 and alterations of its partner signaling molecules (the decrease in p-Akt, nuclear NF-κB p65, and co-immunoprecipitated cytochrome c/Hsp27 were validated. Hsp27 over-expression protected against bufalin-induced apoptosis, reversed the dephosphorylation of Akt and preserved the level of nuclear NF-κB p65 and co-immunoprecipitated Hsp27/cytochrome c. Moreover, bufalin inhibited MTX-resistant osteosarcoma xenograft growth, and a down-regulation of Hsp27 in vivo was observed. Taken together, bufalin exerted potent anti-osteosarcoma effects in vitro and in vivo, even in MTX resistant osteosarcoma cells. The down-regulation of Hsp27 played a critical role in bufalin-induced apoptosis in osteosarcoma cells. Bufalin may have merit to be a potential chemotherapeutic agent for osteosarcoma, particularly in MTX-resistant groups.

  1. Critical appraisal of the role of glucosamine and chondroitin in the management of osteoarthritis of the knee

    Directory of Open Access Journals (Sweden)

    Steven J Narvy

    2010-02-01

    Full Text Available Steven J Narvy1, C Thomas Vangsness Jr21Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 2Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USAAbstract: Osteoarthritis (OA is the most common musculoskeletal disease in the United States, with rising prevalence. Medical management of OA involves acetaminophen, nonsteroidal anti-inflammatory drugs, and other analgesics, all of which are of variable efficacy and are associated with significant side effects and toxicities. The purpose of this review is to critically evaluate the efficacy of glucosamine and chondroitin, both as single agents and in combination, for the treatment of knee OA. Also evaluated were the level of evidence and funding support of the included articles. Almost every included trial of glucosamine sulfate, glucosamine hydrochloride, and chondroitin sulfate has found the safety of these compounds to be equal to that of placebo, though their therapeutic efficacy in decreasing knee OA pain and improving joint function is variable. Additionally, there are data to support a role of these agents in reducing radiographic progression of knee OA. Industry involvement, however, remains prominent. Further, more comprehensive study by independent researchers free of industry ties is necessary to identify a subset of patients in whom the use of glucosamine and/or chondroitin would be most beneficial. These agents may be safely tried as an initial therapy in select OA patients prior to initiating therapy with nonsteroidal anti-inflammatory drugs, acetaminophen, and other traditional medications.Keywords: glucosamine sulfate, glucosamine hydrochloride, chondroitin sulfate, knee osteoarthritis, nutritional supplement, nutraceutical

  2. Critical role of surface chemical modifications induced by length shortening on multi-walled carbon nanotubes-induced toxicity

    Directory of Open Access Journals (Sweden)

    Bussy Cyrill

    2012-11-01

    Full Text Available Abstract Given the increasing use of carbon nanotubes (CNT in composite materials and their possible expansion to new areas such as nanomedicine which will both lead to higher human exposure, a better understanding of their potential to cause adverse effects on human health is needed. Like other nanomaterials, the biological reactivity and toxicity of CNT were shown to depend on various physicochemical characteristics, and length has been suggested to play a critical role. We therefore designed a comprehensive study that aimed at comparing the effects on murine macrophages of two samples of multi-walled CNT (MWCNT specifically synthesized following a similar production process (aerosol-assisted CVD, and used a soft ultrasonic treatment in water to modify the length of one of them. We showed that modification of the length of MWCNT leads, unavoidably, to accompanying structural (i.e. defects and chemical (i.e. oxidation modifications that affect both surface and residual catalyst iron nanoparticle content of CNT. The biological response of murine macrophages to the two different MWCNT samples was evaluated in terms of cell viability, pro-inflammatory cytokines secretion and oxidative stress. We showed that structural defects and oxidation both induced by the length reduction process are at least as responsible as the length reduction itself for the enhanced pro-inflammatory and pro-oxidative response observed with short (oxidized compared to long (pristine MWCNT. In conclusion, our results stress that surface properties should be considered, alongside the length, as essential parameters in CNT-induced inflammation, especially when dealing with a safe design of CNT, for application in nanomedicine for example.

  3. Numerical Development

    Science.gov (United States)

    Siegler, Robert S.; Braithwaite, David W.

    2016-01-01

    In this review, we attempt to integrate two crucial aspects of numerical development: learning the magnitudes of individual numbers and learning arithmetic. Numerical magnitude development involves gaining increasingly precise knowledge of increasing ranges and types of numbers: from non-symbolic to small symbolic numbers, from smaller to larger…

  4. Hindi Numerals.

    Science.gov (United States)

    Bright, William

    In most languages encountered by linguists, the numerals, considered as a paradigmatic set, constitute a morpho-syntactic problem of only moderate complexity. The Indo-Aryan language family of North India, however, presents a curious contrast. The relatively regular numeral system of Sanskrit, as it has developed historically into the modern…

  5. Numerical analysis

    CERN Document Server

    Rao, G Shanker

    2006-01-01

    About the Book: This book provides an introduction to Numerical Analysis for the students of Mathematics and Engineering. The book is designed in accordance with the common core syllabus of Numerical Analysis of Universities of Andhra Pradesh and also the syllabus prescribed in most of the Indian Universities. Salient features: Approximate and Numerical Solutions of Algebraic and Transcendental Equation Interpolation of Functions Numerical Differentiation and Integration and Numerical Solution of Ordinary Differential Equations The last three chapters deal with Curve Fitting, Eigen Values and Eigen Vectors of a Matrix and Regression Analysis. Each chapter is supplemented with a number of worked-out examples as well as number of problems to be solved by the students. This would help in the better understanding of the subject. Contents: Errors Solution of Algebraic and Transcendental Equations Finite Differences Interpolation with Equal Intervals Interpolation with Unequal Int...

  6. The Influence of Collaborative Group Work on Students' Development of Critical Thinking: The Teacher's Role in Facilitating Group Discussions

    Science.gov (United States)

    Fung, Dennis Chun-Lok; To, Helen; Leung, Kit

    2016-01-01

    The objective of this study was to determine whether the incorporation of group work in a teaching intervention can effectively foster students' critical thinking skills. Building upon Kuhn's critical thinking model, the research involved comparison of pretest and post-test results for 140 secondary four (10th grade) students in Hong Kong on two…

  7. Has dopamine a physiological role in the control of sexual behavior? A critical review of the evidence.

    Science.gov (United States)

    Paredes, Raúl G; Agmo, Anders

    2004-06-01

    The role of dopaminergic systems in the control of sexual behavior has been a subject of study for at least 40 years. Not surprisingly, reviews of the area have been published at variable intervals. However, the earlier reviews have been summaries of published research rather than a critical analysis of it. They have focused upon the conclusions presented in the original research papers rather than on evaluating the reliability and functional significance of the data reported to support these conclusions. During the last few years, important new knowledge concerning dopaminergic systems and their behavioral functions as well as the possible role of these systems in sexual behavior has been obtained. For the first time, it is now possible to integrate the data obtained in studies of sexual behavior into the wider context of general dopaminergic functions. To make this possible, we first present an analysis of the nature and organization of sexual behavior followed by a summary of current knowledge about the brain structures of crucial importance for this behavior. We then proceed with a description of the dopaminergic systems within or projecting to these structures. Whenever possible, we also try to include data on the electrophysiological actions of dopamine. Thereafter, we proceed with analyses of pharmacological data and release studies, both in males and in females. Consistently throughout this discussion, we make an effort to distinguish pharmacological effects on sexual behavior from a possible physiological role of dopamine. By pharmacological effects, we mean here drug-induced alterations in behavior that are not the result of the normal actions of synaptically released dopamine in the untreated animal. The conclusion of this endeavor is that pharmacological effects of dopaminergic drugs are variable in both males and females, independently of whether the drugs are administered systemically or intracerebrally. We conclude that the pharmacological data

  8. Reappraisal of criticality for two-layer flows and its role in the generation of internal solitary waves

    Science.gov (United States)

    Bridges, Thomas J.; Donaldson, Neil M.

    2007-07-01

    A geometric view of criticality for two-layer flows is presented. Uniform flows are classified by diagrams in the momentum-massflux space for fixed Bernoulli energy, and cuspoidal curves on these diagrams correspond to critical uniform flows. Restriction of these surfaces to critical flow leads to new subsurfaces in energy-massflux space. While the connection between criticality and the generation of solitary waves is well known, we find that the nonlinear properties of these bifurcating solitary waves are also determined by the properties of the criticality surfaces. To be specific, the case of two layers with a rigid lid is considered, and application of the theory to other multilayer flows is sketched.

  9. The Possibility of Film Criticism.

    Science.gov (United States)

    Poague, Leland; Cadbury, William

    1989-01-01

    Examines the role of critical language in film criticism. Compares and contrasts Monroe Beardsley's philosophy on film aesthetics with the New Criticism. Outlines some of the contributions Beardsley has made to the study of film criticism. (KM)

  10. Critical structural and functional roles for the N-terminal insertion sequence in surfactant protein B analogs.

    Directory of Open Access Journals (Sweden)

    Frans J Walther

    2010-01-01

    Full Text Available Surfactant protein B (SP-B; 79 residues belongs to the saposin protein superfamily, and plays functional roles in lung surfactant. The disulfide cross-linked, N- and C-terminal domains of SP-B have been theoretically predicted to fold as charged, amphipathic helices, suggesting their participation in surfactant activities. Earlier structural studies with Mini-B, a disulfide-linked construct based on the N- and C-terminal regions of SP-B (i.e., approximately residues 8-25 and 63-78, confirmed that these neighboring domains are helical; moreover, Mini-B retains critical in vitro and in vivo surfactant functions of the native protein. Here, we perform similar analyses on a Super Mini-B construct that has native SP-B residues (1-7 attached to the N-terminus of Mini-B, to test whether the N-terminal sequence is also involved in surfactant activity.FTIR spectra of Mini-B and Super Mini-B in either lipids or lipid-mimics indicated that these peptides share similar conformations, with primary alpha-helix and secondary beta-sheet and loop-turns. Gel electrophoresis demonstrated that Super Mini-B was dimeric in SDS detergent-polyacrylamide, while Mini-B was monomeric. Surface plasmon resonance (SPR, predictive aggregation algorithms, and molecular dynamics (MD and docking simulations further suggested a preliminary model for dimeric Super Mini-B, in which monomers self-associate to form a dimer peptide with a "saposin-like" fold. Similar to native SP-B, both Mini-B and Super Mini-B exhibit in vitro activity with spread films showing near-zero minimum surface tension during cycling using captive bubble surfactometry. In vivo, Super Mini-B demonstrates oxygenation and dynamic compliance that are greater than Mini-B and compare favorably to full-length SP-B.Super Mini-B shows enhanced surfactant activity, probably due to the self-assembly of monomer peptide into dimer Super Mini-B that mimics the functions and putative structure of native SP-B.

  11. The role of amputation as an outcome measure in cellular therapy for critical limb ischemia: implications for clinical trial design

    Directory of Open Access Journals (Sweden)

    Pearl Gregory J

    2011-09-01

    Full Text Available Abstract Background Autologous bone marrow-derived stem cells have been ascribed an important therapeutic role in No-Option Critical limb Ischemia (NO-CLI. One primary endpoint for evaluating NO-CLI therapy is major amputation (AMP, which is usually combined with mortality for AMP-free survival (AFS. Only a trial which is double blinded can eliminate physician and patient bias as to the timing and reason for AMP. We examined factors influencing AMP in a prospective double-blinded pilot RCT (2:1 therapy to control of 48 patients treated with site of service obtained bone marrow cells (BMAC as well as a systematic review of the literature. Methods Cells were injected intramuscularly in the CLI limbs as either BMAC or placebo (peripheral blood. Six month AMP rates were compared between the two arms. Both patient and treating team were blinded of the assignment in follow-up examinations. A search of the literature identified 9 NO-CLI trials, the control arms of which were used to determine 6 month AMP rates and the influence of tissue loss. Results Fifteen amputations occurred during the 6 month period, 86.7% of these during the first 4 months. One amputation occurred in a Rutherford 4 patient. The difference in amputation rate between patients with rest pain (5.6% and those with tissue loss (46.7%, irrespective of treatment group, was significant (p = 0.0029. In patients with tissue loss, treatment with BMAC demonstrated a lower amputation rate than placebo (39.1% vs. 71.4%, p = 0.1337. The Kaplan-Meier time to amputation was longer in the BMAC group than in the placebo group (p = 0.067. Projecting these results to a pivotal trial, a bootstrap simulation model showed significant difference in AFS between BMAC and placebo with a power of 95% for a sample size of 210 patients. Meta-analysis of the literature confirmed a difference in amputation rate between patients with tissue loss and rest pain. Conclusions BMAC shows promise in improving AMP

  12. Numerical analysis

    CERN Document Server

    Scott, L Ridgway

    2011-01-01

    Computational science is fundamentally changing how technological questions are addressed. The design of aircraft, automobiles, and even racing sailboats is now done by computational simulation. The mathematical foundation of this new approach is numerical analysis, which studies algorithms for computing expressions defined with real numbers. Emphasizing the theory behind the computation, this book provides a rigorous and self-contained introduction to numerical analysis and presents the advanced mathematics that underpin industrial software, including complete details that are missing from most textbooks. Using an inquiry-based learning approach, Numerical Analysis is written in a narrative style, provides historical background, and includes many of the proofs and technical details in exercises. Students will be able to go beyond an elementary understanding of numerical simulation and develop deep insights into the foundations of the subject. They will no longer have to accept the mathematical gaps that ex...

  13. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections

    NARCIS (Netherlands)

    Tangden, T.; Martin, V.; Felton, T.W.; Nielsen, E.I.; Marchand, S.; Bruggemann, R.J.M.; Bulitta, J.B.; Bassetti, M.; Theuretzbacher, U.; Tsuji, B.T.; Wareham, D.W.; Friberg, L.E.; Waele, J.J. De; Tam, V.H.; Roberts, J.A.

    2017-01-01

    Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed.

  14. The Role of Parents' Critical Thinking About Media in Shaping Expectancies, Efficacy and Nutrition Behaviors for Families.

    Science.gov (United States)

    Austin, Erica Weintraub; Pinkleton, Bruce E; Radanielina-Hita, Marie Louise; Ran, Weina

    2015-01-01

    A convenience survey completed online by 137 4-H parents in Washington state explored their orientation toward critical thinking regarding media sources and content and its implications for family dietary behaviors. Parents' critical thinking toward media sources predicted their information efficacy about content. Critical thinking toward media content predicted information efficacy about sources, expectancies for parental mediation, and expectancies for family receptiveness to lower-fat dietary changes. Expectancies for receptiveness to dietary changes and expectancies for parental mediation predicted efficacy for implementing healthy dietary practices; this strongly predicted healthy dietary practices. Media-related critical thinking, therefore, indirectly but consistently affected self-reported family dietary behaviors through its effects on efficacy for managing media and expectancies for the family's receptiveness to healthy dietary changes. The results suggest parents' media literacy skills affect their family's dietary behavior. Health campaigns that help parents interpret and manage the media environment may benefit all family members.

  15. Role of brain-derived neurotrophic factor in the excitatory-inhibitory imbalance during the critical period of postnatal respiratory development in the rat.

    Science.gov (United States)

    Gao, Xiu-Ping; Zhang, Hanmeng; Wong-Riley, Margaret

    2015-11-01

    The critical period of respiratory development in rats is a narrow window toward the end of the second postnatal week (P12-13), when abrupt neurochemical, electrophysiological, and ventilatory changes occur, when inhibition dominates over excitation, and when the animals' response to hypoxia is the weakest. The goal of this study was to further test our hypothesis that a major mechanism underlying the synaptic imbalance during the critical period is a reduced expression of brain-derived neurotrophic factor (BDNF) and its TrkB receptors. Our aims were to determine (1) that the inhibitory dominance observed in hypoglossal motoneurons during the critical period was also demonstrable in a key respiratory chemosensor, NTSVL; (2) if in vivo application of a TrkB agonist, 7,8-DHF, would prevent, but a TrkB antagonist, ANA-12, would accentuate the synaptic imbalance; and (3) if hypoxia would also heighten the imbalance. Our results indicate that (1) the synaptic imbalance was evident in the NTSVL during the critical period; (2) intraperitoneal injections of 7,8-DHF prevented the synaptic imbalance during the critical period, whereas ANA-12 in vivo accentuated such an imbalance; and (3) acute hypoxia induced the weakest response in both the amplitude and frequency of sEPSCs during the critical period, but it increased the frequency of sIPSCs during the critical period. Thus, our findings are consistent with and strengthen our hypothesis that BDNF and TrkB play a significant role in inducing a synaptic imbalance during the critical period of respiratory development in the rat. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. The Role of Critical Pedagogy in the Globalization Era and the Aftermath of September 11, 2001. Interview with Peter McLaren (Updated Version

    Directory of Open Access Journals (Sweden)

    Lucía Coral Aguirre Muñoz

    2003-05-01

    Full Text Available In the face of postmodern theories claiming the end of the working class, Peter McLaren discusses the globalization of capitalism as a form of imperialism; he does so from a critical perspective founded on Marxist theory and on the concepts of social class and class struggle. Regarding the events of September 11, 2001, he describes U.S. foreign policy and its effects at the international level. He also defends the heroic figure of Che Guevara against accusations by some US critics that Che should be compared to Bin Laden. The conclusion of this analysis defines the role of critical pedagogy in education, whose purpose is that of contributing to the creation of an egalitarian society based on the socialist values of cooperation and solidarity.

  17. Numerical modelling of lithospheric flexure in front of subduction zones in Japan and its role to initiate melt extraction from the LVZ.

    Science.gov (United States)

    Bessat, A.; Pilet, S.; Duretz, T.; Schmalholz, S. M.

    2017-12-01

    Petit-spot volcanoes were found fifteen years ago by Japanese researchers at the top of the subducting plate in Japan (Hirano 2006). This discovery is of great significance as it highlights the importance of tectonic processes for the initiation of intraplate volcanism. The location of these small lava flows is unusual and seems to be related to the plate flexure, which may facilitate the extraction of low degree melts from the base of the lithosphere, a hypothesis previously suggested to explain changes in electric and seismic properties at 70-90 km depth, i.e. within the low velocity zone (LVS) (Sifré 2014). A critical question is related to the process associated with the extraction of this low degree melts from the LVZ. First models suggested that extension associated to plate bending allows large cracks to propagate across the lithosphere and could promote the extraction of low degree melts at the base of the lithosphere (Hirano 2006 & Yamamoto 2014). However, the study of petit-spot mantle xenoliths from Japan (Pilet 2016) has demonstrated that low degree melts are not directly extracted to the surface but percolate, interact and metasomatize the oceanic lithosphere. In order to understand the melt extraction process in the region of plate bending, we performed 2D thermo-mechanical simulations of Japanese-type subduction. The numerical model considers viscoelastoplastic deformation. This allows the quantification of state of the stress, strain rates, and viscosities which will control the percolation of melt initially stocked at the base of the lithosphere. Initial results show that plate flexure changes the distribution of the deformation mechanism in the flexure zone, between 40 km to 80 km depth. A change of the dominant deformation mechanism from diffusion creep to dislocation creep and from there to Peierls creep was observed about 200 to 300 km from the trench. These changes are linked to the augmentation of the stresses in the flexure zone. At the

  18. The Key-Role of shielding analysis in advanced Candu Fuel bundles nuclear safety improvement for some accidental criticality scenarios

    International Nuclear Information System (INIS)

    Margeanu, C.A.; Rizoiu, A.; Olteanu, G.

    2008-01-01

    The paper aims to present the source term and photon dose rates estimation for advanced Candu fuel bundles in some accidental criticality scenarios. As reference, the Candu standard fuel bundle has been used. The scenarios take into account for a very short-time irradiated or spent fuel bundles for some configurations closed to criticality. In order to estimate irradiated fuel characteristic parameters and radiation doses, the ORNL's SCALE 5 codes Origin-S and Monte Carlo MORSE-SGC have been used. The paper includes the irradiated fuel characteristic parameters comparison for the considered Candu fuel bundles, providing also a comparison between the corresponding radiation doses

  19. Numerical analysis

    CERN Document Server

    Brezinski, C

    2012-01-01

    Numerical analysis has witnessed many significant developments in the 20th century. This book brings together 16 papers dealing with historical developments, survey papers and papers on recent trends in selected areas of numerical analysis, such as: approximation and interpolation, solution of linear systems and eigenvalue problems, iterative methods, quadrature rules, solution of ordinary-, partial- and integral equations. The papers are reprinted from the 7-volume project of the Journal of Computational and Applied Mathematics on '/homepage/sac/cam/na2000/index.html<

  20. Advanced practice nursing role delineation in acute and critical care: application of the strong model of advanced practice.

    Science.gov (United States)

    Mick, D J; Ackerman, M H

    2000-01-01

    This purpose of this study was to differentiate between the roles of clinical nurse specialists and acute care nurse practitioners. Hypothesized blending of the clinical nurse specialist and acute care nurse practitioner roles is thought to result in an acute care clinician who integrates the clinical skills of the nurse practitioner with the systems knowledge, educational commitment, and leadership ability of the clinical nurse specialist. Ideally, this role blending would facilitate excellence in both direct and indirect patient care. The Strong Model of Advanced Practice, which incorporates practice domains of direct comprehensive care, support of systems, education, research, and publication and professional leadership, was tested to search for practical evidence of role blending. This descriptive, exploratory, pilot study included subjects (N = 18) solicited from an academic medical center and from an Internet advanced practice listserv. Questionnaires included self-ranking of expertise in practice domains, as well as valuing of role-related tasks. Content validity was judged by an expert panel of advanced practice nurses. Analyses of descriptive statistics revealed that clinical nurse specialists, who had more experience both as registered nurses and in the advanced practice nurse role, self-ranked their expertise higher in all practice domains. Acute care nurse practitioners placed higher importance on tasks related to direct comprehensive care, including conducting histories and physicals, diagnosing, and performing diagnostic procedures, whereas clinical nurse specialists assigned greater importance to tasks related to education, research, and leadership. Levels of self-assessed clinical expertise as well as valuing of role-related tasks differed among this sample of clinical nurse specialists and acute care nurse practitioners. Groundwork has been laid for continuing exploration into differentiation in advanced practice nursing roles. As the clinical

  1. The Impeding Role of Self-Critical Perfectionism on Therapeutic Alliance During Treatment and Eating Disorder Symptoms at Follow-up in Patients with an Eating Disorder

    Directory of Open Access Journals (Sweden)

    Jolene van der Kaap-Deeder

    2016-04-01

    Full Text Available This study examines the impeding role of self-critical perfectionism at onset of treatment on therapeutic alliance during treatment and eating disorder symptoms at follow-up in patients with an eating disorder. Participants were 53 female patients with a mean age of 21.1 years treated for an eating disorder in a specialized inpatient treatment unit. Self-critical perfectionism was assessed at admission, therapeutic alliance was assessed during treatment (after three months of treatment, and eating disorder symptoms were assessed at admission, after three months and one year later. Self-critical perfectionism negatively related to treatment alliance with the therapist. Although self-critical perfectionism was not directly predictive of subsequent changes in eating disorder symptoms, it was indirectly related to less reduction in body dissatisfaction through the therapeutic alliance. These results point to the importance of self-critical perfectionism in the therapeutic alliance and in changes in body image problems. Treatment implications are discussed.

  2. The role of multisensor data fusion in neuromuscular control of a sagittal arm with a pair of muscles using actor-critic reinforcement learning method.

    Science.gov (United States)

    Golkhou, V; Parnianpour, M; Lucas, C

    2004-01-01

    In this study, we consider the role of multisensor data fusion in neuromuscular control using an actor-critic reinforcement learning method. The model we use is a single link system actuated by a pair of muscles that are excited with alpha and gamma signals. Various physiological sensor information such as proprioception, spindle sensors, and Golgi tendon organs have been integrated to achieve an oscillatory movement with variable amplitude and frequency, while achieving a stable movement with minimum metabolic cost and coactivation. The system is highly nonlinear in all its physical and physiological attributes. Transmission delays are included in the afferent and efferent neural paths to account for a more accurate representation of the reflex loops. This paper proposes a reinforcement learning method with an Actor-Critic architecture instead of middle and low level of central nervous system (CNS). The Actor in this structure is a two layer feedforward neural network and the Critic is a model of the cerebellum. The Critic is trained by the State-Action-Reward-State-Action (SARSA) method. The Critic will train the Actor by supervisory learning based on previous experiences. The reinforcement signal in SARSA is evaluated based on available alternatives concerning the concept of multisensor data fusion. The effectiveness and the biological plausibility of the present model are demonstrated by several simulations. The system showed excellent tracking capability when we integrated the available sensor information. Addition of a penalty for activation of muscles resulted in much lower muscle coactivation while keeping the movement stable.

  3. Design, System, Value: The Role of Problem-Solving and Critical Thinking Capabilities in Technology Education, as Perceived by Teachers

    Science.gov (United States)

    Schooner, Patrick; Nordlöf, Charlotta; Klasander, Claes; Hallström, Jonas

    2017-01-01

    The Organisation for Economic Co-operation and Development (OECD, 2013) defines its views on necessary skills for 21st century citizenship and life-long learning, advocating a generic skillset of literacy, numeracy, and problem-solving in technology-rich environments. Other sources also include critical thinking as a vital 21st Century skill.…

  4. Using Critical Incidents of Instructional Design and Multimedia Production Activities to Investigate Instructional Designers' Current Practices and Roles

    Science.gov (United States)

    Sugar, William A.; Luterbach, Kenneth J.

    2016-01-01

    Through consideration of critical incidents, this study analyzed 106 effective, ineffective and extraordinary instructional design and multimedia production (MP) activities discussed by 36 instructional design professionals. This evaluation provided insights into these professionals' best and not so best practices during the past 6 months.…

  5. The role of network theory and object-oriented modeling within a framework for the vulnerability analysis of critical infrastructures

    International Nuclear Information System (INIS)

    Eusgeld, Irene; Kroeger, Wolfgang; Sansavini, Giovanni; Schlaepfer, Markus; Zio, Enrico

    2009-01-01

    A framework for the analysis of the vulnerability of critical infrastructures has been proposed by some of the authors. The framework basically consists of two successive stages: (i) a screening analysis for identifying the parts of the critical infrastructure most relevant with respect to its vulnerability and (ii) a detailed modeling of the operational dynamics of the identified parts for gaining insights on the causes and mechanisms responsible for the vulnerability. In this paper, a critical presentation is offered of the results of a set of investigations aimed at evaluating the potentials of (i) using network analysis based on measures of topological interconnection and reliability efficiency, for the screening task; (ii) using object-oriented modeling as the simulation framework to capture the detailed dynamics of the operational scenarios involving the most vulnerable parts of the critical infrastructure as identified by the preceding network analysis. A case study based on the Swiss high-voltage transmission system is considered. The results are cross-compared and evaluated; the needs of further research are defined

  6. The role of critical ethnic awareness and social support in the discrimination-depression relationship among Asian Americans: path analysis.

    Science.gov (United States)

    Kim, Isok

    2014-01-01

    This study used a path analytic technique to examine associations among critical ethnic awareness, racial discrimination, social support, and depressive symptoms. Using a convenience sample from online survey of Asian American adults (N = 405), the study tested 2 main hypotheses: First, based on the empowerment theory, critical ethnic awareness would be positively associated with racial discrimination experience; and second, based on the social support deterioration model, social support would partially mediate the relationship between racial discrimination and depressive symptoms. The result of the path analysis model showed that the proposed path model was a good fit based on global fit indices, χ²(2) = 4.70, p = .10; root mean square error of approximation = 0.06; comparative fit index = 0.97; Tucker-Lewis index = 0.92; and standardized root mean square residual = 0.03. The examinations of study hypotheses demonstrated that critical ethnic awareness was directly associated (b = .11, p Asian Americans. This study highlights the usefulness of the critical ethnic awareness concept as a way to better understand how Asian Americans might perceive and recognize racial discrimination experiences in relation to its mental health consequences.

  7. The effect of the marketing-R&D interface on new product performance: The critical role of resources and scope

    NARCIS (Netherlands)

    Leenders, M.A.A.M.; Wierenga, B.

    2008-01-01

    Although the integration of marketing with R&D is widely recognized as a critical factor for a new product's success, this study shows that not all companies benefit equally from more integration. Using data from the worldwide pharmaceutical industry, the authors show that integration is

  8. The Critical Shapes of Body Image: The Role of Culture and Family in the Production of Eating Disorders.

    Science.gov (United States)

    Haworth-Hoeppner, Susan

    2000-01-01

    Explores how the family mediates cultural ideas about thinness, and considers how these messages are conveyed to family members. Discusses open-ended interviews with 32 White, middle-class women on the topic of body image and eating problems. Determined that a critical family environment, coercive parental control, and a dominating discourse on…

  9. Numerical Relativity

    Science.gov (United States)

    Baker, John G.

    2009-01-01

    Recent advances in numerical relativity have fueled an explosion of progress in understanding the predictions of Einstein's theory of gravity, General Relativity, for the strong field dynamics, the gravitational radiation wave forms, and consequently the state of the remnant produced from the merger of compact binary objects. I will review recent results from the field, focusing on mergers of two black holes.

  10. Numerical analysis II essentials

    CERN Document Server

    REA, The Editors of; Staff of Research Education Association

    1989-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Numerical Analysis II covers simultaneous linear systems and matrix methods, differential equations, Fourier transformations, partial differential equations, and Monte Carlo methods.

  11. Intensive care survivors' experiences of ward-based care: Meleis' theory of nursing transitions and role development among critical care outreach services.

    Science.gov (United States)

    Ramsay, Pam; Huby, Guro; Thompson, Andrew; Walsh, Tim

    2014-03-01

    To explore the psychosocial needs of patients discharged from intensive care, the extent to which they are captured using existing theory on transitions in care and the potential role development of critical care outreach, follow-up and liaison services. Intensive care patients are at an increased risk of adverse events, deterioration or death following ward transfer. Nurse-led critical care outreach, follow-up or liaison services have been adopted internationally to prevent these potentially avoidable sequelae. The need to provide patients with psychosocial support during the transition to ward-based care has also been identified, but the evidence base for role development is currently limited. Twenty participants were invited to discuss their experiences of ward-based care as part of a broader study on recovery following prolonged critical illness. Psychosocial distress was a prominent feature of their accounts, prompting secondary data analysis using Meleis et al.'s mid-range theory on experiencing transitions. Participants described a sense of disconnection in relation to profound debilitation and dependency and were often distressed by a perceived lack of understanding, indifference or insensitivity among ward staff to their basic care needs. Negotiating the transition between dependence and independence was identified as a significant source of distress following ward transfer. Participants varied in the extent to which they were able to express their needs and negotiate recovery within professionally mediated boundaries. These data provide new insights into the putative origins of the psychosocial distress that patients experience following ward transfer. Meleis et al.'s work has resonance in terms of explicating intensive care patients' experiences of psychosocial distress throughout the transition to general ward-based care, such that the future role development of critical care outreach, follow-up and liaison services may be more theoretically informed

  12. Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review

    OpenAIRE

    Freedland Eric S

    2004-01-01

    Abstract There are likely many scenarios and pathways that can lead to metabolic syndrome. This paper reviews mechanisms by which the accumulation of visceral adipose tissue (VAT) may contribute to the metabolic syndrome, and explores the paradigm of a critical VAT threshold (CVATT). Exceeding the CVATT may result in a number of metabolic disturbances such as insulin resistance to glucose uptake by cells. Metabolic profiles of patients with visceral obesity may substantially improve after onl...

  13. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections.

    Science.gov (United States)

    Tängdén, T; Ramos Martín, V; Felton, T W; Nielsen, E I; Marchand, S; Brüggemann, R J; Bulitta, J B; Bassetti, M; Theuretzbacher, U; Tsuji, B T; Wareham, D W; Friberg, L E; De Waele, J J; Tam, V H; Roberts, Jason A

    2017-07-01

    Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate antimicrobial concentrations at the site of infection and is associated with poor patient outcomes. In this article, we describe the potential of in vitro and in vivo infection models, clinical pharmacokinetic data and pharmacokinetic/pharmacodynamic models to guide the design of more effective antimicrobial dosing regimens. Individualised dosing, based on population PK models and patient factors (e.g. renal function and weight) known to influence antimicrobial PK, increases the probability of achieving therapeutic drug exposures while at the same time avoiding toxic concentrations. When therapeutic drug monitoring (TDM) is applied, early dose adaptation to the needs of the individual patient is possible. TDM is likely to be of particular importance for infected critically ill patients, where profound PK changes are present and prompt appropriate antibiotic therapy is crucial. In the light of the continued high mortality rates in critically ill patients with severe infections, a paradigm shift to refined dosing strategies for antimicrobials is warranted to enhance the probability of achieving drug concentrations that increase the likelihood of clinical success.

  14. Parental criticism and externalizing behavior problems in adolescents: the role of environment and genotype-environment correlation.

    Science.gov (United States)

    Narusyte, Jurgita; Neiderhiser, Jenae M; Andershed, Anna-Karin; D'Onofrio, Brian M; Reiss, David; Spotts, Erica; Ganiban, Jody; Lichtenstein, Paul

    2011-05-01

    Genetic factors are important for the association between parental negativity and child problem behavior, but it is not clear whether this is due to passive or evocative genotype-environment correlation (rGE). In this study, we applied the extended children-of-twins model to directly examine the presence of passive and evocative rGE as well as direct environmental effects in the association between parental criticism and adolescent externalizing problem behavior. The cross-sectional data come from the Twin and Offspring Study in Sweden (N = 909 pairs of adult twins) and from the Twin Study of Child and Adolescent Development (N = 915 pairs of twin children). The results revealed that maternal criticism was primarily due to evocative rGE emanating from their adolescent's externalizing behavior. On the other hand, fathers' critical remarks tended to affect adolescent problem behavior in a direct environmental way. This suggests that previously reported differences in caretaking between mothers and fathers also are reflected in differences in why parenting is associated with externalizing behavior in offspring.

  15. Parental criticism and externalizing behavior problems in adolescents– the role of environment and genotype-environment correlation

    Science.gov (United States)

    Narusyte, Jurgita; Neiderhiser, Jenae M.; Andershed, Anna-Karin; D’Onofrio, Brian M.; Reiss, David; Spotts, Erica; Ganiban, Jody; Lichtenstein, Paul

    2011-01-01

    Genetic factors are important for the association between parental negativity and child problem behavior, but it is not clear whether this is dueto passive or evocative genotype-environment correlation (rGE). In this study we applied the extended children-of-twins model to directly examine the presence of passive and evocative rGE as well as direct environmental effects in the association between parental criticism and adolescent externalizing problem behavior. The cross-sectional data come from the Twin and Offspring Study in Sweden (TOSS) (N=909 pairs of adult twins) and from the Twin study of CHild and Adolescent Development (TCHAD) (N=915 pairs of twin children). The results revealed that maternal criticism was primarily due to evocative rGE emanating from their adolescent’s externalizing behavior. On the other hand, fathers’ critical remarks tended to affect adolescent problem behavior in a direct environmental way. This suggests that previously reported differences in caretaking between mothers and fathers also are reflected in differences in why parenting is associated with externalizing behavior in offspring. PMID:21280930

  16. Eventual sport performance level: What about the role of type of sport, perception of critical life events, and practice quality?

    Science.gov (United States)

    Toering, Tynke

    2017-01-01

    The target article describes an interesting study, which provides some challenging findings regarding athletes' pathway to excellence. The suggested links between critical life events, need for success, personal characteristics, and eventual performance level make sense from a psychodynamic perspective. This commentary will discuss some critical points related to the application of the findings in talent identification and -development programs. These are (1) the possible effect of the selection of participants on the results (including the impact of dependence on others for team sport athletes and the opportunity for multiple medal attainment), (2) a lack of detail in the description of how the athletes approached the critical life events (the perception of an event may contribute more to development than the event itself), and (3) a lack of detail in the description of the practice process throughout development. Some interesting differences were found in the motivation for and approach to practice, but little detail was given about what the athletes exactly were doing at the time. The concept of self-regulated learning may be useful in explaining how super-elite athletes action their goals through quality practice. © 2017 Elsevier B.V. All rights reserved.

  17. Inhibitory processes for critical situations – The role of n-2 task repetition costs in human multitasking situations

    Directory of Open Access Journals (Sweden)

    Miriam eGade

    2012-05-01

    Full Text Available The human cognitive system is equipped with various processes for dealing with everyday challenges. One of such processes is the inhibition of currently irrelevant goals or mental task sets, which can be seen as a response to the critical event of information overflow in the cognitive system and the cognitive system’s inability to keep track of ongoing demands. In two experiments, we investigate the flexibility of the inhibitory process by inserting rare non-critical events (25% of all trials, operationalized as univalent stimuli (i.e., unambiguous stimuli that call for only one specific task in a multitasking context, and by introducing the possibility to prepare for an upcoming task (Experiment 2. We found that the inhibitory process is not influenced by a cue informing subjects about the upcoming occurrence of a univalent stimulus. However, the introduction of univalent stimuli allowed preparatory processes to modify the impact of the inhibitory process. Therefore, our results suggest that inhibitory processes are engaged in a rather global manner, not taking into account variations in stimulus valence, which we took as operationalization of critical, conflict-inducing events in the ongoing stream of information processing. However, rare uncritical events, such as univalent stimuli that do not cause conflict and interference in the processing stream, appear to alter the way the cognitive system can take advantage of preparatory processes.

  18. Numerical relativity

    CERN Document Server

    Nakamura, T

    1993-01-01

    In GR13 we heard many reports on recent. progress as well as future plans of detection of gravitational waves. According to these reports (see the report of the workshop on the detection of gravitational waves by Paik in this volume), it is highly probable that the sensitivity of detectors such as laser interferometers and ultra low temperature resonant bars will reach the level of h ~ 10—21 by 1998. in this level we may expect the detection of the gravitational waves from astrophysical sources such as coalescing binary neutron stars once a year or so. Therefore the progress in numerical relativity is urgently required to predict the wave pattern and amplitude of the gravitational waves from realistic astrophysical sources. The time left for numerical relativists is only six years or so although there are so many difficulties in principle as well as in practice.

  19. Comparing Psychology Undergraduates' Performance in Probabilistic Reasoning under Verbal-Numerical and Graphical-Pictorial Problem Presentation Format: What Is the Role of Individual and Contextual Dimensions?

    Science.gov (United States)

    Agus, Mirian; Peró-Cebollero, Maribel; Penna, Maria Pietronilla; Guàrdia-Olmos, Joan

    2015-01-01

    This study aims to investigate about the existence of a graphical facilitation effect on probabilistic reasoning. Measures of undergraduates' performances on problems presented in both verbal-numerical and graphical-pictorial formats have been related to visuo-spatial and numerical prerequisites, to statistical anxiety, to attitudes towards…

  20. Nutritional status plays a crucial role in the mortality of critically ill patients with acute renal failure.

    Science.gov (United States)

    Zhang, Haiyan; Zhang, Xiaodong; Dong, Lei

    2018-02-01

    We aimed to clarify associations between nutritional status and mortality in patients with acute renal failure. De-identified data were obtained from the Medical Information Mart for Intensive Care III database comprising more than 40,000 critical care patients treated at Beth Israel Deaconess Medical Centerbetween 2001 and 2012. Weight loss and body mass index criteria were used to define malnutrition. Data of 193 critically ill patients with acute renal failure were analyzed, including demographics, nutrition intervention, laboratory results, and disease severity. Main outcomes were in-hospital and 1-year mortality. The 1-year mortality was significantly higher in those with malnutrition than in those without malnutrition (50.0% vs 29.3%, p=0.010), but differences in in-hospital survival were not significant (p=0.255). Significant differences in mortality were found between those with malnutrition and without starting at the 52nd day after intensive care unit (ICU) discharge (p=0.036). No significant differences were found between men and women with malnutrition in in-hospital mortality (p=0.949) and 1-year mortality (p=0.051). Male patients requiring intervention with blood products/colloid supplements had greater risk of 1-year mortality, but without statistical significance. Nutritional status is a predictive factor for mortality among critically ill patients with acute renal failure, particularly 1-year mortality after ICU discharge. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. The role and strategy of IMRT in radiotherapy of pelvic tumors: Dose escalation and critical organ sparing in prostate cancer

    International Nuclear Information System (INIS)

    Liu, Y.-M.; Shiau, C.-Y.; Lee, M.-L.; Huang, P.-I.; Hsieh, C.-M.; Chen, P.-H.; Lin, Y.-H.; Wang, L.-W.; Yen, S.-H.

    2007-01-01

    Purpose: To investigate the intensity-modulated radiotherapy (IMRT) strategy in dose escalation of prostate and pelvic lymph nodes. Methods and Materials: Plan dosimetric data of 10 prostate cancer patients were compared with two-dimensional (2D) or IMRT techniques for pelvis (two-dimensional whole pelvic radiation therapy [2D-WPRT] or IM-WPRT) to receive 50 Gy or 54 Gy and additional prostate boost by three-dimensional conformal radiation therapy or IMRT (3D-PBRT or IM-PBRT) techniques up to 72 Gy or 78 Gy. Dose-volume histograms (DVHs), normal tissue complication probabilities (NTCP) of critical organ, and conformity of target volume in various combinations were calculated. Results: In DVH analysis, the plans with IM-WPRT (54 Gy) and additional boost up to 78 Gy had lower rectal and bladder volume percentage at 50 Gy and 60 Gy, compared with those with 2D-WPRT (50 Gy) and additional boost up to 72 Gy or 78 Gy. Those with IM-WPRT (54 Gy) also had better small bowel sparing at 30 Gy and 50 Gy, compared with those with 2D-WPRT (50 Gy). In NTCP, those with IM-WPRT and total dose of 78 Gy achieved lower complication rates in rectum and small bowel, compared with those of 2D-WPRT with total dose of 72 Gy. In conformity, those with IM-WPRT had better conformity compared with those with 2D-WPRT with significance (p < 0.005). No significant difference in DVHs, NTCP, or conformity was found between IM-PBRT and 3D-PBRT after IM-WPRT. Conclusions: Initial pelvic IMRT is the most important strategy in dose escalation and critical organ sparing. IM-WPRT is recommended for patients requiring WPRT. There is not much benefit for critical organ sparing by IMRT after 2D-WPRT

  2. THE ROLE OF THE SCHOOL CURRICULUM IN HUMAN DEVELOPMENT: CONTRIBUTIONS OF HISTORICAL AND CRITICAL PEDAGOGY AND PSYCHOLOGY OF HISTORICAL AND CULTURAL

    Directory of Open Access Journals (Sweden)

    Julia Malanchen

    2013-12-01

    Full Text Available This work points to the articulations between the fundamentals of cultural-historical psychology and the historical-critical pedagogy, in regard the issue of content that should compose the curriculum. The correct organization of the teaching process by the teacher, through scientific knowledge, as well as the appropriation of classic content, by students, promotes mental development to raise the development of higher psychological functions at their highest possibilities. Thus, we affirm the cultural-historical psychology and the historical-critical pedagogy align themselves both with regard to the Marxist perspective of socialist revolution, as in respect to concept of formation of individuality and the role of schooling in human emancipation.

  3. The Role of Critical Pedagogy in the Globalization Era and the Aftermath of September 11, 2001. Interview with Peter McLaren

    Directory of Open Access Journals (Sweden)

    Lucía Coral Aguirre Muñoz

    2001-11-01

    Full Text Available In the face of postmodern theories claiming the end of the working class, Peter McLaren discusses globalization as a form of imperialism; he does so from a critical perspective founded on the Marxist theory and on the concept of social class. Regarding the events of September 11, 2001, he describes U.S. foreign policy and its effects at the international level. He contrasts Bin Laden and Che Guevara, highlighting the differences between the two figures. The conclusion of his analysis defines the role of critical pedagogy in education, whose purpose is that of contributing to the creation of an egalitarian society based on the values of cooperation and solidarity.

  4. Review article: the role of gastrointestinal hormones in the treatment of delayed gastric emptying in critically ill patients

    NARCIS (Netherlands)

    Luttikhold, J.; Ruijter, de F.M.; Norren, van K.; Diamant, M.; Witkamp, R.F.; Leeuwen, P.A.M.; Vermeulen, M.A.R.

    2013-01-01

    Background The role of diet in inflammatory bowel disease (IBD) is supported by migration studies and increasing incidences in line with Westernisation. Aim To give a complete overview of studies associating habitual diet with the onset or relapses in ulcerative colitis (UC) or Crohn's disease (CD).

  5. Plastid ribosomal protein S5 plays a critical role in photosynthesis, plant development, and cold stress tolerance in arabidopsis

    Science.gov (United States)

    Plastid ribosomal proteins (RPs) are essential components for protein synthesis machinery and exert diverse roles in plant growth and development. Mutations in plastid RPs lead to a range of developmental phenotypes in plants. However, how they regulate these processes is not fully understood and th...

  6. Critical role of fatty acid metabolism in ILC2 mediated barrier protection during malnutrition and helminth infection

    Science.gov (United States)

    Innate lymphoid cells (ILCs) play an important role in many immune processes, including control of infections, inflammation and tissue repair. To date little is known about the metabolism of ILCs under steady-state conditions and infection, and whether these cells can metabolically adapt in response...

  7. Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1

    NARCIS (Netherlands)

    Singhmar, Pooja; Huo, XiaoJiao; Eijkelkamp, Niels; Berciano, Susana Rojo; Baameur, Faiza; Mei, Fang C; Zhu, Yingmin; Cheng, Xiaodong; Hawke, David; Mayor, Federico; Murga, Cristina; Heijnen, Cobi J.; Kavelaars, Annemieke

    2016-01-01

    cAMP signaling plays a key role in regulating pain sensitivity. Here, we uncover a previously unidentified molecular mechanism in which direct phosphorylation of the exchange protein directly activated by cAMP 1 (EPAC1) by G protein kinase 2 (GRK2) suppresses Epac1-to-Rap1 signaling, thereby

  8. CriticalEd

    DEFF Research Database (Denmark)

    Kjellberg, Caspar Mølholt; Meredith, David

    2014-01-01

    . Since the comments are not input sequentially, with regard to position, but in arbitrary order, this list must be sorted by copy/pasting the rows into place—an error-prone and time-consuming process. Scholars who produce critical editions typically use off-the-shelf music notation software......The best text method is commonly applied among music scholars engaged in producing critical editions. In this method, a comment list is compiled, consisting of variant readings and editorial emendations. This list is maintained by inserting the comments into a document as the changes are made......, consisting of a Sibelius plug-in, a cross-platform application, called CriticalEd, and a REST-based solution, which handles data storage/retrieval. A prototype has been tested at the Danish Centre for Music Publication, and the results suggest that the system could greatly improve the efficiency...

  9. Structural plasticity in mesencephalic dopaminergic neurons produced by drugs of abuse: critical role of BDNF and dopamine.

    Directory of Open Access Journals (Sweden)

    Ginetta eCollo

    2014-11-01

    Full Text Available Mesencephalic dopaminergic neurons were suggested to be a critical physiopathology substrate for addiction disorders. Among neuroadaptive processes to addictive drugs, structural plasticity has attracted attention. While structural plasticity occurs at both pre- and post-synaptic levels in the mesolimbic dopaminergic system, the present review focuses only on dopaminergic neurons. Exposures to addictive drugs determine two opposite structural responses, hypothrophic plasticity produced by opioids and cannabinoids (in particular during the early withdrawal phase and hypertrophic plasticity, mostly driven by psychostimulants and nicotine. In vitro and in vivo studies indentified BDNF and extracellular dopamine as two critical factors in determining structural plasticity, the two molecules sharing similar intracellular pathways involved in cell soma and dendrite growth, the MEK-ERK1/2 and the PI3K-Akt-mTOR, via preferential activation of TrkB and dopamine D3 receptors, respectively. At present information regarding specific structural changes associated to the various stages of the addiction cycle is incomplete. Encouraging neuroimaging data in humans indirectly support the preclinical evidence of hypotrophic and hypertrophic effects, suggesting a possible differential engagement of dopamine neurons in parallel and partially converging circuits controlling motivation, stress and emotions.

  10. Tracking protons from respiratory chain complexes to ATP synthase c-subunit: The critical role of serine and threonine residues.

    Science.gov (United States)

    Panfoli, Isabella; Ponassi, Marco; Ravera, Silvia; Calzia, Daniela; Beitia, Maider; Morelli, Alessandro; Rosano, Camillo

    2017-01-22

    F 1 F o -ATP synthase is a multisubunit enzyme responsible for the synthesis of ATP. Among its multiple subunits (8 in E. coli, 17 in yeast S. cerevisiae, 16 in vertebrates), two subunits a and c are known to play a central role controlling the H + flow through the inner mitochondrial membrane which allows the subsequent synthesis of ATP, but the pathway followed by H + within the two proteins is still a matter of debate. In fact, even though the structure of ATP synthase is now well defined, the molecular mechanisms determining the function of both F 1 and F O domains are still largely unknown. In this study, we propose a pathway for proton migration along the ATP synthase by hydrogen-bonded chain mechanism, with a key role of serine and threonine residues, by X-ray diffraction data on the subunit a of E. coli Fo. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Critical role of the virus-encoded microRNA-155 ortholog in the induction of Marek's disease lymphomas.

    Directory of Open Access Journals (Sweden)

    Yuguang Zhao

    2011-02-01

    Full Text Available Notwithstanding the well-characterised roles of a number of oncogenes in neoplastic transformation, microRNAs (miRNAs are increasingly implicated in several human cancers. Discovery of miRNAs in several oncogenic herpesviruses such as KSHV has further highlighted the potential of virus-encoded miRNAs to contribute to their oncogenic capabilities. Nevertheless, despite the identification of several possible cancer-related genes as their targets, the direct in vivo role of virus-encoded miRNAs in neoplastic diseases such as those induced by KSHV is difficult to demonstrate in the absence of suitable models. However, excellent natural disease models of rapid-onset Marek's disease (MD lymphomas in chickens allow examination of the oncogenic potential of virus-encoded miRNAs. Using viruses modified by reverse genetics of the infectious BAC clone of the oncogenic RB-1B strain of MDV, we show that the deletion of the six-miRNA cluster 1 from the viral genome abolished the oncogenicity of the virus. This loss of oncogenicity appeared to be primarily due to the single miRNA within the cluster, miR-M4, the ortholog of cellular miR-155, since its deletion or a 2-nucleotide mutation within its seed region was sufficient to inhibit the induction of lymphomas. The definitive role of this miR-155 ortholog in oncogenicity was further confirmed by the rescue of oncogenic phenotype by revertant viruses that expressed either the miR-M4 or the cellular homolog gga-miR-155. This is the first demonstration of the direct in vivo role of a virus-encoded miRNA in inducing tumors in a natural infection model. Furthermore, the use of viruses deleted in miRNAs as effective vaccines against virulent MDV challenge, enables the prospects of generating genetically defined attenuated vaccines.

  12. The role of interfacial defects in enhancing the critical current density of YBa2Cu3O7-delta coatings

    Energy Technology Data Exchange (ETDEWEB)

    Foltyn, Stephen R [Los Alamos National Laboratory; Wang, Haiyan [Los Alamos National Laboratory; Civale, Leonardo [Los Alamos National Laboratory; Maiorov, Boris A [Los Alamos National Laboratory; Jia, Quanxi [Los Alamos National Laboratory

    2009-01-01

    The critical current density (J{sub c}) of YBa{sub 2}Cu{sub 3}0{sub 7-{delta}} (YBCO) films can approach 10 MA/cm{sup 2} at 77 K in self field , but only for very thin films. We have shown previously that strong thickness dependence results if J{sub c} is enhanced near the film-substrate interface. In the present work we investigate interfacial enhancement using laser-deposited YBCO films on NdGaO{sub 3} substrates, and find that we can adjust deposition conditions to switch the enhancement on and off. Interestingly, we find that the 'on' state is accompanied by interfacial misfit dislocations, establishing an unambiguous correlation between enhanced J{sub c} and dislocations at the film-substrate interface.

  13. Role of Side-Chain Molecular Features in Tuning Lower Critical Solution Temperatures (LCSTs) of Oligoethylene Glycol Modified Polypeptides.

    Science.gov (United States)

    Gharakhanian, Eric G; Deming, Timothy J

    2016-07-07

    A series of thermoresponsive polypeptides has been synthesized using a methodology that allowed facile adjustment of side-chain functional groups. The lower critical solution temperature (LCST) properties of these polymers in water were then evaluated relative to systematic molecular modifications in their side-chains. It was found that in addition to the number of ethylene glycol repeats in the side-chains, terminal and linker groups also have substantial and predictable effects on cloud point temperatures (Tcp). In particular, we found that the structure of these polypeptides allowed for inclusion of polar hydroxyl groups, which significantly increased their hydrophilicity and decreased the need to use long oligoethylene glycol repeats to obtain LCSTs. The thioether linkages in these polypeptides were found to provide an additional structural feature for reversible switching of both polypeptide conformation and thermoresponsive properties.

  14. Brucella cyclic β-1,2-glucan plays a critical role in the induction of splenomegaly in mice.

    Directory of Open Access Journals (Sweden)

    Mara S Roset

    Full Text Available Brucella, the etiological agent of animal and human brucellosis, is a bacterium with the capacity to modulate the inflammatory response. Cyclic β-1,2-glucan (CβG is a virulence factor key for the pathogenesis of Brucella as it is involved in the intracellular life cycle of the bacteria. Using comparative studies with different CβG mutants of Brucella, cgs (CβG synthase, cgt (CβG transporter and cgm (CβG modifier, we have identified different roles for this polysaccharide in Brucella. While anionic CβG is required for bacterial growth in low osmolarity conditions, the sole requirement for a successful Brucella interaction with mammalian host is its transport to periplasmic space. Our results uncover a new role for CβG in promoting splenomegaly in mice. We showed that CβG-dependent spleen inflammation is the consequence of massive cell recruitment (monocytes, dendritics cells and neutrophils due to the induction of pro-inflammatory cytokines such as IL-12 and TNF-α and also that the reduced splenomegaly response observed with the cgs mutant is not the consequence of changes in expression levels of the characterized Brucella PAMPs LPS, flagellin or OMP16/19. Complementation of cgs mutant with purified CβG increased significantly spleen inflammation response suggesting a direct role for this polysaccharide.

  15. A Critical Review of the Oversight Role of the Office of the Auditor-General in Financial Accountability

    Directory of Open Access Journals (Sweden)

    Ogochukwu Nzewi

    2014-03-01

    Full Text Available Accountability is the very essence of the Constitution of the Republic of South Africa (Act No. 108 of 1996. In this regard, the Auditor-General of South Africa (AGSA as the supreme audit institution of the Republic of South Africa plays an important oversight role of promoting financial accountability in government. The purpose of this article is to examine the challenges facing the office of the Auditor-General in executing its oversight role of promoting financial accountability in the sphere of provincial government. Information and sources for this article was gathered through literature review. The article gives some background on the establishment and rationale of Supreme Audit Institutions (SAI. It explores some policy framework that informs public finance management in the Republic of South Africa, establishing the role of the AGSA within this purview. Based on the data gathered through literature review, the key challenges facing the office of the Auditor-General are discussed. Finally, possible solutions are recommended to the challenges that were identified.

  16. Critical role of LuxS in the virulence of Campylobacter jejuni in a guinea pig model of abortion.

    Science.gov (United States)

    Plummer, Paul; Sahin, Orhan; Burrough, Eric; Sippy, Rachel; Mou, Kathy; Rabenold, Jessica; Yaeger, Mike; Zhang, Qijing

    2012-02-01

    Previous studies on Campylobacter jejuni have demonstrated the role of LuxS in motility, cytolethal distending toxin production, agglutination, and intestinal colonization; however, its direct involvement in virulence has not been reported. In this study, we demonstrate a direct role of luxS in the virulence of C. jejuni in two different animal hosts. The IA3902 strain, a highly virulent sheep abortion strain recently described by our laboratory, along with its isogenic luxS mutant and luxS complement strains, was inoculated by the oral route into both a pregnant guinea pig virulence model and a chicken colonization model. In both cases, the IA3902 luxS mutant demonstrated a complete loss of ability to colonize the intestinal tract. In the pregnant model, the mutant also failed to induce abortion, while the wild-type strain was highly abortifacient. Genetic complementation of the luxS gene fully restored the virulent phenotype in both models. Interestingly, when the organism was inoculated into guinea pigs by the intraperitoneal route, no difference in virulence (abortion induction) was observed between the luxS mutant and the wild-type strain, suggesting that the defect in virulence following oral inoculation is likely associated with a defect in colonization and/or translocation of the organism out of the intestine. These studies provide the first direct evidence that LuxS plays an important role in the virulence of C. jejuni using an in vivo model of natural disease.

  17. Crossing borders: a critical review of the role of the European Court of Justice in EU health policy.

    Science.gov (United States)

    Brooks, Eleanor

    2012-04-01

    Over the last two decades, the European Union (EU) has steadily increased its involvement in the health policies of its member states, with considerable support from the European Court of Justice (ECJ). However, much of the literature examining the Court's role has focused upon the intersection between internal market law and the health services sector; the majority of studies have failed to examine the potential role for the Court in public health policy. Observers such as Greer have seen the development of healthcare as a clear case of neofunctional spillover, a view supported but qualified by Wasserfallen and others, who present a more detailed account of the mechanics of the process. Alternative analyses have focused upon the new modes of governance, soft law and other factors - this article reviews the current state of research in the field and the extent to which it should concern health policy actors and non-specialists in EU policy alike. It concludes that the Court has played and continues to play a crucial role in the development of EU public health policy, as well as in health services and broader social policy, where its influence has already been well documented. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Diet quality can play a critical role in defense efficacy against parasitoids and pathogens in the Glanville fritillary (Melitaea cinxia).

    Science.gov (United States)

    Laurentz, Minna; Reudler, Joanneke H; Mappes, Johanna; Friman, Ville; Ikonen, Suvi; Lindstedt, Carita

    2012-01-01

    Numerous herbivorous insect species sequester noxious chemicals from host plants that effectively defend against predators, and against parasitoids and pathogens. Sequestration of these chemicals may be expensive and involve a trade off with other fitness traits. Here, we tested this hypothesis. We reared Glanville fritillary butterfly (Melitaea cinxia L.) larvae on plant diets containing low- and high-levels of iridoid glycosides (IGs) (mainly aucubin and catalpol) and tested: 1) whether IGs affect the herbivore's defense against parasitoids (measured as encapsulation rate) and bacterial pathogens (measured as herbivore survival); 2) whether parasitoid and bacterial defenses interact; and 3) whether sequestration of the plant's defense chemicals incurs any life history costs. Encapsulation rates were stronger when there were higher percentages of catalpol in the diet. Implanted individuals had greater amounts of IGs in their bodies as adults. This suggests that parasitized individuals may sequester more IGs, increase their feeding rate after parasitism, or that there is a trade off between detoxification efficiency and encapsulation rate. Larval survival after bacterial infection was influenced by diet, but probably not by diet IG content, as changes in survival did not correlate linearly with the levels of IGs in the diet. However, M. cinxia larvae with good encapsulation abilities were better defended against bacteria. We did not find any life history costs of diet IG concentration for larvae. These results suggest that the sequestering of plant defense chemicals can help herbivorous insects to defend against parasitoids.

  19. Transcriptomic analysis of Portunus trituberculatus reveals a critical role for WNT4 and WNT signalling in limb regeneration.

    Science.gov (United States)

    Liu, Lei; Fu, Yuanyuan; Zhu, Fang; Mu, Changkao; Li, Ronghua; Song, Weiwei; Shi, Ce; Ye, Yangfang; Wang, Chunlin

    2018-06-05

    The swimming crab (Portunus trituberculatus) is among the most economically important seawater crustacean species in Asia. Despite its commercial importance and being well-studied status, genomic and transcriptomic data are scarce for this crab species. In the present study, limb bud tissue was collected at different developmental stages post amputation for transcriptomic analysis. Illumina RNA-sequencing was applied to characterise the limb regeneration transcriptome and identify the most characteristic genes. A total of 289,018 transcripts were obtained by clustering and assembly of clean reads, producing 150,869 unigenes with an average length of 956 bp. Subsequent analysis revealed WNT signalling as the key pathway involved in limb regeneration, with WNT4 a key mediator. Overall, limb regeneration appears to be regulated by multiple signalling pathways, with numerous cell differentiation, muscle growth, moult, metabolism, and immune-related genes upregulated, including WNT4, LAMA, FIP2, FSTL5, TNC, HUS1, SWI5, NCGL, SLC22, PLA2, Tdc2, SMOX, GDH, and SMPD4. This is the first experimental study done on regenerating claws of P. trituberculatus. These findings expand existing sequence resources for crab species, and will likely accelerate research into regeneration and development in crustaceans, particularly functional studies on genes involved in limb regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Numerical mathematics

    National Research Council Canada - National Science Library

    Quarteroni, Alfio; Sacco, Riccardo; Saleri, Fausto

    2000-01-01

    ... for their qualitative and quantitative analysis. This role is also emphasized by the continual development of computers and algorithms, which make it possible nowadays, using scientific computing, to tackle problems of such a large size that real-life phenomena can be simulated providing accurate responses at affordable computational cost. The corresp...

  1. Numerical analysis

    CERN Document Server

    Jacques, Ian

    1987-01-01

    This book is primarily intended for undergraduates in mathematics, the physical sciences and engineering. It introduces students to most of the techniques forming the core component of courses in numerical analysis. The text is divided into eight chapters which are largely self-contained. However, with a subject as intricately woven as mathematics, there is inevitably some interdependence between them. The level of difficulty varies and, although emphasis is firmly placed on the methods themselves rather than their analysis, we have not hesitated to include theoretical material when we consider it to be sufficiently interesting. However, it should be possible to omit those parts that do seem daunting while still being able to follow the worked examples and to tackle the exercises accompanying each section. Familiarity with the basic results of analysis and linear algebra is assumed since these are normally taught in first courses on mathematical methods. For reference purposes a list of theorems used in the t...

  2. A critical role of lateral hypothalamus in context-induced relapse to alcohol seeking after punishment-imposed abstinence.

    Science.gov (United States)

    Marchant, Nathan J; Rabei, Rana; Kaganovsky, Konstantin; Caprioli, Daniele; Bossert, Jennifer M; Bonci, Antonello; Shaham, Yavin

    2014-05-28

    In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA + GABAB receptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse. Copyright © 2014 the authors 0270-6474/14/347447-11$15.00/0.

  3. A Critical Role for the Nucleus Reuniens in Long-Term, But Not Short-Term Associative Recognition Memory Formation.

    Science.gov (United States)

    Barker, Gareth R I; Warburton, Elizabeth Clea

    2018-03-28

    Recognition memory for single items requires the perirhinal cortex (PRH), whereas recognition of an item and its associated location requires a functional interaction among the PRH, hippocampus (HPC), and medial prefrontal cortex (mPFC). Although the precise mechanisms through which these interactions are effected are unknown, the nucleus reuniens (NRe) has bidirectional connections with each regions and thus may play a role in recognition memory. Here we investigated, in male rats, whether specific manipulations of NRe function affected performance of recognition memory for single items, object location, or object-in-place associations. Permanent lesions in the NRe significantly impaired long-term, but not short-term, object-in-place associative recognition memory, whereas single item recognition memory and object location memory were unaffected. Temporary inactivation of the NRe during distinct phases of the object-in-place task revealed its importance in both the encoding and retrieval stages of long-term associative recognition memory. Infusions of specific receptor antagonists showed that encoding was dependent on muscarinic and nicotinic cholinergic neurotransmission, whereas NMDA receptor neurotransmission was not required. Finally, we found that long-term object-in-place memory required protein synthesis within the NRe. These data reveal a specific role for the NRe in long-term associative recognition memory through its interactions with the HPC and mPFC, but not the PRH. The delay-dependent involvement of the NRe suggests that it is not a simple relay station between brain regions, but, rather, during high mnemonic demand, facilitates interactions between the mPFC and HPC, a process that requires both cholinergic neurotransmission and protein synthesis. SIGNIFICANCE STATEMENT Recognizing an object and its associated location, which is fundamental to our everyday memory, requires specific hippocampal-cortical interactions, potentially facilitated by the

  4. The Trombe Wall during the 1970s: technological device or architectural space? Critical inquiry on the Trombe Wall in Europe and the role of architectural magazines

    Directory of Open Access Journals (Sweden)

    Piero Medici

    2017-12-01

    Full Text Available During the 1970s, before and after the international oil crisis of 1973, some European architectural periodicals were critical of standard construction methods and the architecture of the time. They described how architects and engineers reacted to the crisis, proposing new techniques and projects in order to intervene innovatively in the built environment, using energy and natural resources more efficiently. This article will provide a critical analysis of the role of architectural magazines of the time, describing the technological innovation of the Trombe Wall in Europe. It will treat when, how, and what specific aspects were described. It will also carry out a critical analysis of the Trombe Wall itself: about its performances, its evolution throughout the 1970s, its integration in different houses, and its influence on inhabitants’ behaviour. Using three houses as case studies, an analysis of the architects’ efforts to integrate the technology of the Trombe Wall with architectural elements such as shape, aesthetic, materiality, and natural light will be carried out. Though this article is historical in character, it aims to inform the contemporary debate, especially concerning issues of the built environment meeting the Paris agreement on climate change (AA, 2015.

  5. The Development of Self-Criticism and Dependency in Early Adolescence and Their Role in the Development of Depressive and Anxiety Symptoms.

    Science.gov (United States)

    Kopala-Sibley, Daniel C; Zuroff, David C; Hankin, Benjamin L; Abela, John R Z

    2015-08-01

    According to Blatt and others (e.g., A. T. Beck), self-definition, or one's sense of self, and one's sense of relatedness to others represent core lifespan developmental tasks. This study examined the role of events pertaining to self-definition or relatedness in the development of personality traits from each domain (self-criticism and dependency), and their relationship to the development of depressive and anxiety symptoms. Two hundred seventy-six early adolescents completed a measure of self-criticism and dependency at baseline and again 24 months later, along with measures of depressive and anxiety symptoms. Every 3 months, participants completed a measure of life events, which were coded as self-definitional or relatedness oriented (80% rater agreement, kappa = .70). Structural equation models showed that self-definitional events predicted increases in self-criticism, which in turn predicted increases in depressive symptoms, whereas relatedness events predicted increases in dependency, although dependency was unrelated to change in symptoms. © 2015 by the Society for Personality and Social Psychology, Inc.

  6. Non invasive adjustment of fluid status in critically ill patients on renal replacement therapy. Role of Electrical Cardiometry

    Directory of Open Access Journals (Sweden)

    Khaled Hamed Mahmoud

    2016-08-01

    Full Text Available Background: Electrical Cardiometry allows measurement of fluid status using thoracic fluid content (TFC, cardiac output, cardiac index, systemic vascular resistance index which could be ideal noninvasive hemodynamic monitoring for patients undergoing hemodialysis (HD. Objectives: Investigating the relation between changes in TFC and amount of fluid removal during HD session and to monitor hemodynamic parameters to avoid episodes of hemodynamic compromise during HD session. Methods: Thirty critically ill patients on HD were enrolled. Clinical assessment of volume overload and hemodynamics (BP, MAP, CVP, monitored by Electrical Cardiometry ICON® before HD and all through sessions. Results: Out of studied patients males represented 46.7% (n = 14 with mean age 48 ± 16 years. There was positive correlation between UF volume and TFC (r = 0.410, P = 0.025. Out of the 30 pts studied 18 pts (60% were hemodynamically stable vs 12 pts (40% that had hypotension represented by non responders group and had lower TFC compared to the hemodynamically stable group (26.45 kohm−1 vs 37.8 kohm−1 with P value of 0.004 indicating that they were hypovolemic. Out of the 30 pts studied 18 pts (60% weren’t congested vs 12 pts (40% remained persistently congested after accomplishing HD session with significantly higher TFC when compared to those who got rid of congestion (43.14 ± 9.9 kohm−1 vs 25.44 ± 5.5 kohm−1 with P value of 0.0001 indicating that they were still hypervolemic. Using analysis of ROC curve TFC at 25.34 kohm−1 was a significant predictor of hypotension with P value of 0.002, AUC 83.4%, sensitivity 67% and specificity 100%. Also TFC cutoff value predicting persistent congestion was 37.02 kohm−1 with P value of 0.0001, AUC 95.8%, sensitivity 83% and specificity 100%. Conclusion: Electrical Cardiometry is an evolving noninvasive tool for adjusting fluid status of critically ill patient on RRT using thoracic fluid

  7. Critical role of FcR gamma-chain, LAT, PLCgamma2 and thrombin in arteriolar thrombus formation upon mild, laser-induced endothelial injury in vivo.

    Science.gov (United States)

    Kalia, Neena; Auger, Jocelyn M; Atkinson, Ben; Watson, Steve P

    2008-05-01

    The role of collagen receptor complex GPVI-FcR gamma-chain, PLCgamma2 and LAT in laser-induced thrombosis is unclear. Controversy surrounds whether collagen is exposed in this model or whether thrombosis is dependent on thrombin. This study hypothesized that collagen exposure plays a critical role in thrombus formation in this model, which was tested by investigating contributions of FcR gamma-chain, LAT, PLCgamma2 and thrombin. Thrombi were monitored using intravital microscopy in anesthetized wild-type and FcR gamma-chain, LAT and PLCgamma2 knockout mice. Hirudin (thrombin inhibitor) was administered to wild-type and FcR gamma-chain knockout mice. Significantly reduced thrombus formation was observed in FcR gamma-chain and PLCgamma2 knockouts with a greater decrease observed in LAT knockouts. Dramatic reduction was observed in wild-types treated with hirudin, with abolished thrombus formation only observed in FcR gamma-chain knockouts treated with hirudin. GPVI-FcR gamma-chain, LAT and PLCgamma2 are essential for thrombus generation and stability in this laser-induced model of injury. More importantly, a greater role for LAT was identified, which may reflect a role for it downstream of a second matrix protein receptor. However, inhibition of platelet activation by matrix proteins and thrombin generation are both required to maximally prevent thrombus formation.

  8. The Arabidopsis nox mutant lacking carotene hydroxylase activity reveals a critical role for xanthophylls in photosystem I biogenesis.

    Science.gov (United States)

    Dall'Osto, Luca; Piques, Maria; Ronzani, Michela; Molesini, Barbara; Alboresi, Alessandro; Cazzaniga, Stefano; Bassi, Roberto

    2013-02-01

    Carotenes, and their oxygenated derivatives xanthophylls, are essential components of the photosynthetic apparatus. They contribute to the assembly of photosynthetic complexes and participate in light absorption and chloroplast photoprotection. Here, we studied the role of xanthophylls, as distinct from that of carotenes, by characterizing a no xanthophylls (nox) mutant of Arabidopsis thaliana, which was obtained by combining mutations targeting the four carotenoid hydroxylase genes. nox plants retained α- and β-carotenes but were devoid in xanthophylls. The phenotype included depletion of light-harvesting complex (LHC) subunits and impairment of nonphotochemical quenching, two effects consistent with the location of xanthophylls in photosystem II antenna, but also a decreased efficiency of photosynthetic electron transfer, photosensitivity, and lethality in soil. Biochemical analysis revealed that the nox mutant was specifically depleted in photosystem I function due to a severe deficiency in PsaA/B subunits. While the stationary level of psaA/B transcripts showed no major differences between genotypes, the stability of newly synthesized PsaA/B proteins was decreased and translation of psaA/B mRNA was impaired in nox with respect to wild-type plants. We conclude that xanthophylls, besides their role in photoprotection and LHC assembly, are also needed for photosystem I core translation and stability, thus making these compounds indispensable for autotrophic growth.

  9. The role of lymph node dissection in the contemporary management of renal cell carcinoma: A critical appraisal of the evidence.

    Science.gov (United States)

    Brito, Joseph; Gershman, Boris

    2017-11-01

    The role of lymph node dissection (LND) in the management of renal cell carcinoma has been controversial. Older studies provided initial support to a potential survival benefit in resection of lymph node metastases, and several predictive models were developed to identify patients with lymph node involvement. However, the only randomized trial on the subject did not report a survival benefit to LND in the nonmetastatic setting. Several studies have recently reexplored the therapeutic benefit of LND. In both nonmetastatic and metastatic settings, LND does not appear to be associated with a survival benefit. Moreover, it does not appear that LND confers a survival advantage to patients at increased risk of lymph node metastases, such as those with preoperative radiographic lymphadenopathy or across increasing probability of lymph node disease. Among patients with clinically isolated lymph node metastases, the majority develop disease progression following surgical resection, suggesting a high prevalence of occult systemic disease. Lymph node metastases appear to have prognostic value in both nonmetastatic and metastatic settings. LND may, therefore, have an increasingly important staging role in the management of renal cell carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The role of nailfold capillaroscopy in the assessment of internal organ involvement in systemic sclerosis: A critical review.

    Science.gov (United States)

    Soulaidopoulos, Stergios; Triantafyllidou, Eva; Garyfallos, Alexandros; Kitas, George D; Dimitroulas, Theodoros

    2017-08-01

    Endothelial dysfunction and microvascular damage constitute the hallmarks of systemic sclerosis (SSc), explaining much of the pathophysiology and clinical manifestations of the disease. Nailfold videocapillaroscopy (NVC) is an established method for the assessment of the microvasculature, aiding in distinguishing different types of structural vascular abnormalities. Until recently, NVC was used in the diagnosis of SSc as well as in the assessment and follow-up of peripheral digital vasculopathy. On the top of digital ulcers, internal organ involvement such as myocardial dysfunction, pulmonary vascular and/or parenchymal lung disease characterizes severe SSc imparting a high risk of mortality. There is growing evidence suggesting that the extent of peripheral microvascular changes reflects the severity of the disease, especially in terms of life-threatening cardiopulmonary complications. The possible use of nailfold videocapillaroscopy as a useful, non-invasive modality to improve the ability to identify patients at higher risk for these devastating complications of the disease remains to be established. The aim of this review is to critically summarize and discuss current literature regarding the relationship between morphological alterations of nailfold dermal papillary vessels and several manifestations of SSc, focusing on visceral organ involvement, as well as their association with surrogate markers of macrovascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. A critical role of platelet TGF-β release in podoplanin-mediated tumour invasion and metastasis.

    Science.gov (United States)

    Takemoto, Ai; Okitaka, Mina; Takagi, Satoshi; Takami, Miho; Sato, Shigeo; Nishio, Makoto; Okumura, Sakae; Fujita, Naoya

    2017-02-08

    The tumour microenvironment is critical for various characteristics of tumour malignancies. Platelets, as part of the tumour microenvironment, are associated with metastasis formation via increasing the rate of tumour embolus formation in microvasculature. However, the mechanisms underlying the ability of tumour cells to acquire invasiveness and extravasate into target organs at the site of embolization remain unclear. In this study, we reported that platelet aggregation-inducing factor podoplanin expressed on tumour cell surfaces were found to not only promote the formation of tumour-platelet aggregates via interaction with platelets, but also induced the epithelial-mesenchymal transition (EMT) of tumour cells by enhancing transforming growth factor-β (TGF-β) release from platelets. In vitro and in vivo analyses revealed that podoplanin-mediated EMT resulted in increased invasiveness and extravasation of tumour cells. Treatment of mice with a TGF-β-neutralizing antibody statistically suppressed podoplanin-mediated distant metastasis in vivo, suggesting that podoplanin promoted haematogenous metastasis in part by releasing TGF-β from platelets that was essential for EMT of tumour cells. Therefore, our findings suggested that blocking the TGF-β signalling pathway might be a promising strategy for suppressing podoplanin-mediated haematogenous metastasis in vivo.

  12. NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis

    Science.gov (United States)

    Jiang, Zhaozhao; Fortune, Sarah M.; Coulombe, Francois; Behr, Marcel A.; Fitzgerald, Katherine A.; Sassetti, Christopher M.; Kelliher, Michelle A.

    2009-01-01

    While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors, the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane. An important outcome of cytosolic recognition is the induction of IFNα and IFNβ, which are critical mediators of immunity against both bacteria and viruses. Like many intracellular pathogens, a significant fraction of the transcriptional response to Mycobacterium tuberculosis infection depends on these type I interferons, but the recognition pathways responsible remain elusive. In this work, we demonstrate that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that responds to bacterial peptidoglycan, and this event requires membrane damage that is actively inflicted by the bacterium. Unexpectedly, this recognition triggers the expression of type I interferons in a Tbk1- and Irf5-dependent manner. This response is only partially impaired by the loss of Irf3 and therefore, differs fundamentally from those stimulated by bacterial DNA, which depend entirely on this transcription factor. This difference appears to result from the unusual peptidoglycan produced by mycobacteria, which we show is a uniquely potent agonist of the Nod2/Rip2/Irf5 pathway. Thus, the Nod2 system is specialized to recognize bacteria that actively perturb host membranes and is remarkably sensitive to mycobacteria, perhaps reflecting the strong evolutionary pressure exerted by these pathogens on the mammalian immune system. PMID:19578435

  13. Homophilic interactions mediated by receptor tyrosine phosphatases mu and kappa. A critical role for the novel extracellular MAM domain

    DEFF Research Database (Denmark)

    Zondag, G C; Koningstein, G M; Jiang, Y P

    1995-01-01

    and is found in diverse transmembrane proteins, is not known. We previously reported that both RPTP mu and RPTP kappa can mediate homophilic cell interactions when expressed in insect cells. Here we show that despite their striking structural similarity, RPTP mu and RPTP kappa fail to interact...... in a heterophilic manner. To examine the role of the MAM domain in homophilic binding, we expressed a mutant RPTP mu lacking the MAM domain in insect Sf9 cells. Truncated RPTP mu is properly expressed at the cell surface but fails to promote cell-cell adhesion. Homophilic cell adhesion is fully restored...... in a chimeric RPTP mu molecule containing the MAM domain of RPTP kappa. However, this chimeric RPTP mu does not interact with either RPTP mu or RPTP kappa. These results indicate that the MAM domain of RPTP mu and RPTP kappa is essential for homophilic cell-cell interaction and helps determine the specificity...

  14. Critical role for invariant chain in CD1d-mediated selection and maturation of Vα14-invariant NKT cells.

    Science.gov (United States)

    Sillé, Fenna C M; Martin, Constance; Jayaraman, Pushpa; Rothchild, Alissa; Besra, Gurdyal S; Behar, Samuel M; Boes, Marianne

    2011-09-30

    The development and maturation of Vα14 invariant (i)NKT cells in mice requires CD1d-mediated lipid antigen presentation in the thymus and the periphery. Cortical thymocytes mediate positive selection, while professional APCs are involved in thymic negative selection and in terminal maturation of iNKT cells in the periphery. CD1d requires entry in the endosomal pathway to allow antigen acquisition for assembly as lipid/CD1d complexes for display to iNKT cells. This process involves tyrosine-based sorting motifs in the CD1d cytoplasmic tail and invariant chain (Ii) that CD1d associates with in the endoplasmic reticulum. The function of Ii in iNKT cell thymic development and peripheral maturation had not been fully understood. Using mice deficient in Ii and the Ii-processing enzyme cathepsin S (catS), we addressed this question. Ii(-/-) mice but not catS(-/-) mice developed significantly fewer iNKT cells in thymus, that were less mature as measured by CD44 and NK1.1 expression. Ii(-/-) mice but not catS(-/-) mice developed fewer Vβ7(+) cells in their iNKT TCR repertoire than WT counterparts, indicative of a change in endogenous glycolipid antigen/CD1d-mediated iNKT cell selection. Finally, using a Mycobacterium tuberculosis infection model in macrophages, we show that iNKT developed in Ii(-/-) but not catS(-/-) mice have defective effector function. Our data support a role for professional APCs expressing Ii, but no role for catS in the thymic development and peripheral terminal maturation of iNKT cells. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Role of Neogene Exhumation and Sedimentation on Critical-Wedge Kinematics in the Zagros Orogenic Belt, Northeastern Iraq, Kurdistan

    Science.gov (United States)

    Koshnaw, R. I.; Horton, B. K.; Stockli, D. F.; Barber, D. E.; Tamar-Agha, M. Y.; Kendall, J. J.

    2014-12-01

    The Zagros orogenic belt and foreland basin formed during the Cenozoic Arabia-Eurasia collision, but the precise histories of shortening and sediment accumulation remain ambiguous, especially at the NW extent of the fold-thrust belt in Iraqi Kurdistan. This region is characterized by well-preserved successions of Cenozoic clastic foreland-basin fill and deformed Paleozoic-Mesozoic hinterland bedrock. The study area provides an excellent opportunity to investigate the linkage between orogenic wedge behavior and surface processes of erosion and deposition. The aim of this research is to test whether the Zagros orogenic wedge advanced steadily under critical to supercritical wedge conditions involving in-sequence thrusting with minimal erosion or propagated intermittently under subcritical condition involving out-of-sequence deformation with intense erosion. These endmember modes of mountain building can be assessed by integrating geo/thermochronologic and basin analyses techniques, including apatite (U-Th)/He thermochronology, detrital zircon U-Pb geochronology, stratigraphic synthesis, and seismic interpretations. Preliminary apatite (U-Th)/He data indicate activation of the Main Zagros Fault (MZF) at ~10 Ma with frontal thrusts initiating at ~8 Ma. However, thermochronometric results from the intervening Mountain Front Flexure (MFF), located between the MZF and the frontal thrusts, suggest rapid exhumation at ~6 Ma. These results suggest that the MFF, represented by the thrust-cored Qaradagh anticline, represents a major episode of out-of-sequence deformation. Detrital zircon U-Pb analyses from the Neogene foreland-basin deposits show continuous sediment derivation from sources to the NNE in Iraq and western Iran, suggesting that out-of-sequence thrusting did not significantly alter sedimentary provenance. Rather, intense hinterland erosion and recycling of older foreland-basin fill dominated sediment delivery to the basin. The irregular distribution of

  16. Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

    Science.gov (United States)

    Kim, Albert H.; Wakabayashi, Ken T.; Baumann, Michael H.; Shaham, Yavin

    2014-01-01

    MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed “rave” parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22−23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ∼1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues. PMID:24899699

  17. Are boxer shorts really better? A critical analysis of the role of underwear type in male subfertility.

    Science.gov (United States)

    Munkelwitz, R; Gilbert, B R

    1998-10-01

    Elevation of testicular temperature may result in arrest of spermatogenesis, abnormal semen parameters and sterility. It has been proposed that brief style underwear may produce scrotal hyperthermia and lead to clinical subfertility. Although this idea is regarded as dogma by many in the lay community and the changing of underwear type is a therapy frequently recommended by medical practitioners, there is a paucity of data measuring scrotal temperature as a function of underwear type. Scrotal, core and skin temperatures were measured in 97 consecutive men presenting for evaluation of primary clinical subfertility. These cases were categorized by underwear type to boxer or brief group. Semen analyses were obtained in all patients. Individuals from each group were compared to ascertain differences in temperature when wearing and not wearing underwear. Baseline semen parameters also were compared. In 14 subjects (crossover group) underwear type was changed to the alternative type and scrotal temperature measurements were repeated. Literature regarding underwear type, testicular temperature and/or fertility was reviewed and critically analyzed. Mean scrotal temperature plus or minus standard deviation was 33.8 +/- 0.8 C and 33.6 +/- 1.1 C in the boxer and brief group, respectively. There were no significant temperature differences between the groups. Differential temperatures comparing core to scrotal temperature and semen parameters also were not significantly different. These observations remained constant in the crossover group. The hyperthermic effect of brief style underwear has been exaggerated. In our study there was no difference in scrotal temperature depending on underwear type. It is unlikely that underwear type has a significant effect on male fertility. Routinely advising infertility patients to wear boxer shorts cannot be supported by available scientific evidence.

  18. The Rhipicephalus (Boophilus microplus Bm86 gene plays a critical role in the fitness of ticks fed on cattle during acute Babesia bovis infection

    Directory of Open Access Journals (Sweden)

    Knowles Donald P

    2010-11-01

    Full Text Available Abstract Background Rhipicephalus (Boophilus microplus is an economically important tick of cattle involved in the transmission of Babesia bovis, the etiological agent of bovine babesiosis. Commercial anti-tick vaccines based on the R. microplus Bm86 glycoprotein have shown some effect in controlling tick infestation; however their efficacy as a stand-alone solution for tick control has been questioned. Understanding the role of the Bm86 gene product in tick biology is critical to identifying additional methods to utilize Bm86 to reduce R. microplus infestation and babesia transmission. Additionally, the role played by Bm86 in R. microplus fitness during B. bovis infection is unknown. Results Here we describe in two independent experiments that RNA interference-mediated silencing of Bm86 decreased the fitness of R. microplus females fed on cattle during acute B. bovis infection. Notably, Bm86 silencing decreased the number and survival of engorged females, and decreased the weight of egg masses. However, gene silencing had no significant effect on the efficiency of transovarial transmission of B. bovis from surviving female ticks to their larval offspring. The results also show that Bm86 is expressed, in addition to gut cells, in larvae, nymphs, adult males and ovaries of partially engorged adult R. microplus females, and its expression was significantly down-regulated in ovaries of ticks fed on B. bovis-infected cattle. Conclusion The R. microplus Bm86 gene plays a critical role during tick feeding and after repletion during blood digestion in ticks fed on cattle during acute B. bovis infection. Therefore, the data indirectly support the rationale for using Bm86-based vaccines, perhaps in combination with acaricides, to control tick infestation particularly in B. bovis endemic areas.

  19. A critical role for very long-chain fatty acid elongases in oleic acid-mediated Saccharomyces cerevisiae cytotoxicity.

    Science.gov (United States)

    Wang, Qiao; Du, Xiuxiu; Ma, Ke; Shi, Ping; Liu, Wenbin; Sun, Jing; Peng, Min; Huang, Zhiwei

    2018-03-01

    Elongases FEN1/ELO2 and SUR4/ELO3 are important enzymes involved in the elongation of long-chain fatty acids (LCFAs) to very long-chain fatty acids (VLCFAs) in Saccharomyces cerevisiae. The molecular mechanism of the involvement of these elongases in lipotoxicity is unclear. In the present study, we investigated the role of VLCFA elongases in oleic acid-mediated yeast cytotoxicity. The spot test showed that yeast strains with the deletion of ELO2 or ELO3 were strikingly sensitive to oleic acid, while there was no change on the growth of strain with deleted ELO1 which was involved in the elongation of C 14 fatty acid (FA) to C 16 FA. By using GC-MS, the unsaturation index was increased in elo2△ and elo3△ mutants after treatment with oleic acid (OLA). However, the proportion of VLCFAs was increased in response to OLA in the wild-type strain. The growth inhibition of elo2△ and elo3△ could be partially rescued by two commonly used antioxidant agents N-acetyl cysteine (NAC) and Ascorbic acid (VC). The further study showed that exposure to excess OLA led to an increase in the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS), and a decline in the quantity of reduced glutathione (GSH) in both the wild type and mutant strains. However, the antioxidant enzyme activities of superoxide dismutase (SOD) and catalase (CAT) were increased in the wild type and elo1△ strains, while they were significantly decreased in the mutants of elo2△ and elo3△ after treated with excess OLA. Thus, oxidative damage mainly contributed to the cell death induced by OLA in ole2△ and ole3△. Taken together, although disruption of ELO2 or ELO3 did not affect the cellular lipid unsaturation, they altered the distribution and propotion of cellular VLCFAs, leading to the cell membrane impairment, which augmented the ability of OLA to permeabilize the plasma membrane. The data suggest that the very long-chain fatty acids elongases ELO2 and ELO3

  20. M2 Macrophages Play Critical Roles in Progression of Inflammatory Liver Disease in Hepatitis C Virus Transgenic Mice.

    Science.gov (United States)

    Ohtsuki, Takahiro; Kimura, Kiminori; Tokunaga, Yuko; Tsukiyama-Kohara, Kyoko; Tateno, Chise; Hayashi, Yukiko; Hishima, Tsunekazu; Kohara, Michinori

    2016-01-01

    Macrophages in liver tissue are widely defined as important inflammatory cells in chronic viral hepatitis due to their proinflammatory activity. We reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) play significant roles in causing chronic hepatitis in hepatitis C virus (HCV) transgenic mice (S. Sekiguchi et al., PLoS One 7:e51656, 2012, http://dx.doi.org/10.1371/journal.pone.0051656). In addition, we showed that recombinant vaccinia viruses expressing an HCV nonstructural protein (rVV-N25) could protect against the progression of chronic hepatitis by suppression of macrophage activation. Here, we focus on the role of macrophages in liver disease progression in HCV transgenic mice and examine characteristic features of macrophages following rVV-N25 treatment. The number of CD11b(+) F4/80(+) CD11c(-) CD206(+) (M2) macrophages in the liver of HCV transgenic mice was notably increased compared to that of age-matched control mice. These M2 macrophages in the liver produced elevated levels of IL-6 and TNF-α. rVV-N25 infection suppressed the number and activation of M2 macrophages in liver tissue. These results suggested that inflammatory cytokines produced by M2-like macrophages contribute to the induction of chronic liver inflammation in HCV transgenic mice. Moreover, the therapeutic effect of rVV-N25 might be induced by the suppression of the number and activation of hepatic macrophages. HCV causes persistent infections that can lead to chronic liver diseases, liver fibrosis, and hepatocellular carcinoma; the search for an HCV curative is the focus of ongoing research. Recently, effective anti-HCV drugs have been developed; however, vaccine development still is required for the prevention and therapy of infection by this virus. We demonstrate here that M2 macrophages are important for the pathogenesis of HCV-caused liver diseases and additionally show that M2 macrophages contribute to the therapeutic mechanism observed following r

  1. A Non-specific Setaria italica Lipid Transfer Protein Gene Plays a Critical Role under Abiotic Stress.

    Science.gov (United States)

    Pan, Yanlin; Li, Jianrui; Jiao, Licong; Li, Cong; Zhu, Dengyun; Yu, Jingjuan

    2016-01-01

    Lipid transfer proteins (LTPs) are a class of cysteine-rich soluble proteins having small molecular weights. LTPs participate in flower and seed development, cuticular wax deposition, also play important roles in pathogen and abiotic stress responses. A non-specific LTP gene ( SiLTP ) was isolated from a foxtail millet ( Setaria italica ) suppression subtractive hybridization library enriched for differentially expressed genes after abiotic stress treatments. A semi-quantitative reverse transcriptase PCR analysis showed that SiLTP was expressed in all foxtail millet tissues. Additionally, the SiLTP promoter drove GUS expression in root tips, stems, leaves, flowers, and siliques of transgenic Arabidopsis . Quantitative real-time PCR indicated that the SiLTP expression was induced by NaCl, polyethylene glycol, and abscisic acid (ABA). SiLTP was localized in the cytoplasm of tobacco leaf epidermal cells and maize protoplasts. The ectopic expression of SiLTP in tobacco resulted in higher levels of salt and drought tolerance than in the wild type (WT). To further assess the function of SiLTP, SiLTP overexpression (OE) and RNA interference (RNAi)-based transgenic foxtail millet were obtained. SiLTP -OE lines performed better under salt and drought stresses compared with WT plants. In contrast, the RNAi lines were much more sensitive to salt and drought compared than WT. Electrophoretic mobility shift assays and yeast one-hybrids indicated that the transcription factor ABA-responsive DRE-binding protein (SiARDP) could bind to the dehydration-responsive element of SiLTP promoter in vitro and in vivo , respectively. Moreover, the SiLTP expression levels were higher in SiARDP -OE plants compared than the WT. These results confirmed that SiLTP plays important roles in improving salt and drought stress tolerance of foxtail millet, and may partly be upregulated by SiARDP. SiLTP may provide an effective genetic resource for molecular breeding in crops to enhance salt and drought

  2. A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation.

    Directory of Open Access Journals (Sweden)

    Hiroshi Okabe

    2006-12-01

    Full Text Available Cyclin D1 regulates G1 progression. Its transcriptional regulation is well understood. However, the mechanism underlying cyclin D1 ubiquitination and its subsequent degradation is not yet clear. We report that cyclin D1 undergoes increased degradation in the cytoplasm during S phase in a variety of cancer cells. This is mediated by phosphorylation at Thr286 through the activity of the Ras/Raf/MEK/ERK cascade and the F-box protein FBXW8, which is an E3 ligase. The majority of FBXW8 is expressed in the cytoplasm during G1 and S phase. In contrast, cyclin D1 accumulates in the nucleus during G1 phase and exits into the cytoplasm in S phase. Increased cyclin D1 degradation is linked to association with FBXW8 in the cytoplasm, and enhanced phosphorylation of cyclin D1 through sustained ERK1/2 signaling. Depletion of FBXW8 caused a significant accumulation of cyclin D1, as well as sequestration of CDK1 in the cytoplasm. This resulted in a severe reduction of cell proliferation. These effects could be rescued by constitutive nuclear expression of cyclin D1-T286A. Thus, FBXW8 plays an essential role in cancer cell proliferation through proteolysis of cyclin D1. It may present new opportunities to develop therapies targeting destruction of cyclin D1 or its regulator E3 ligase selectively.

  3. The critical role of Astragalus polysaccharides for the improvement of PPARα [ correction of PPRAα]-mediated lipotoxicity in diabetic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    Full Text Available BACKGROUND: Obesity-related diabetes mellitus leads to increased myocardial uptake and oxidation of fatty acids, resulting in a form of cardiac dysfunction referred to as lipotoxic cardiomyopathy. We have shown previously that Astragalus polysaccharides (APS administration was sufficient to improve the systemic metabolic disorder and cardiac dysfunction in diabetic models. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the precise role of APS therapy in the pathogenesis of myocardial lipotoxity in diabetes, db/db diabetic mice and myosin heavy chain (MHC- peroxisome proliferator-activated receptor (PPAR α mice were characterized and administrated with or without APS with C57 wide- type mice as normal control. APS treatment strikingly improved the myocyte triacylglyceride accumulation and cardiac dysfunction in both db/db mice and MHC-PPARα mice, with the normalization of energy metabolic derangements in both db/db diabetic hearts and MHC-PPARα hearts. Consistently, the activation of PPARα target genes involved in myocardial fatty acid uptake and oxidation in both db/db diabetic hearts and MHC-PPARα hearts was reciprocally repressed by APS administration, while PPARα-mediated suppression of genes involved in glucose utilization of both diabetic hearts and MHC-PPARα hearts was reversed by treatment with APS. CONCLUSIONS: We conclude that APS therapy could prevent the development of diabetic cardiomyopathy through a mechanism mainly dependent on the cardiac PPARα-mediated regulatory pathways.

  4. Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution.

    Science.gov (United States)

    Zeng, Ming; Paiardini, Mirko; Engram, Jessica C; Beilman, Greg J; Chipman, Jeffrey G; Schacker, Timothy W; Silvestri, Guido; Haase, Ashley T

    2012-08-30

    Loss of the fibroblastic reticular cell (FRC) network in lymphoid tissues during HIV-1 infection has been shown to impair the survival of naive T cells and limit immune reconstitution after antiretroviral therapy. What causes this FRC loss is unknown. Because FRC loss correlates with loss of both naive CD4 and CD8 T-cell subsets and decreased lymphotoxin-β, a key factor for maintenance of FRC network, we hypothesized that loss of naive T cells is responsible for loss of the FRC network. To test this hypothesis, we assessed the consequences of antibody-mediated depletion of CD4 and CD8 T cells in rhesus macaques and sooty mangabeys. We found that only CD4 T-cell depletion resulted in FRC loss in both species and that this loss was caused by decreased lymphotoxin-β mainly produced by the CD4 T cells. We further found the same dependence of the FRC network on CD4 T cells in HIV-1-infected patients before and after antiretroviral therapy and in other immunodeficiency conditions, such as CD4 depletion in cancer patients induced by chemotherapy and irradiation. CD4 T cells thus play a central role in the maintenance of lymphoid tissue structure necessary for their own homeostasis and reconstitution.

  5. The critical role of point defects in improving the specific capacitance of δ-MnO2 nanosheets

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Peng; Metz, Peter; Hey, Trevyn; Gong, Yuxuan; Liu, Dawei; Edwards, Doreen D.; Howe, Jane Y.; Huang, Rong; Misture, Scott T.

    2017-02-23

    3D porous nanostructures built from 2D δ-MnO2 nanosheets are an environmentally friendly and industrially scalable class of supercapacitor electrode material. While both the electrochemistry and defects of this material have been studied, the role of defects in improving the energy storage density of these materials has not been addressed. In this work, δ-MnO2 nanosheet assemblies with 150 m2 g-1 specific surface area are prepared by exfoliation of crystalline KxMnO2 and subsequent reassembly. Equilibration at different pH introduces intentional Mn vacancies into the nanosheets, increasing pseudocapacitance to over 300 F g-1, reducing charge transfer resistance as low as 3 Ω, and providing a 50% improvement in cycling stability. X-ray absorption spectroscopy and high-energy X-ray scattering demonstrate a correlation between the defect content and the improved electrochemical performance. The results show that Mn vacancies provide ion intercalation sites which concurrently improve specific capacitance, charge transfer resistance and cycling stability.

  6. Critical role of RanBP2-mediated SUMOylation of Small Heterodimer Partner in maintaining bile acid homeostasis

    Science.gov (United States)

    Kim, Dong-Hyun; Kwon, Sanghoon; Byun, Sangwon; Xiao, Zhen; Park, Sean; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Kemper, Byron; Kemper, Jongsook Kim

    2016-01-01

    Bile acids (BAs) are recently recognized signalling molecules that profoundly affect metabolism. Because of detergent-like toxicity, BA levels must be tightly regulated. An orphan nuclear receptor, Small Heterodimer Partner (SHP), plays a key role in this regulation, but how SHP senses the BA signal for feedback transcriptional responses is not clearly understood. We show an unexpected function of a nucleoporin, RanBP2, in maintaining BA homoeostasis through SUMOylation of SHP. Upon BA signalling, RanBP2 co-localizes with SHP at the nuclear envelope region and mediates SUMO2 modification at K68, which facilitates nuclear transport of SHP and its interaction with repressive histone modifiers to inhibit BA synthetic genes. Mice expressing a SUMO-defective K68R SHP mutant have increased liver BA levels, and upon BA- or drug-induced biliary insults, these mice exhibit exacerbated cholestatic pathologies. These results demonstrate a function of RanBP2-mediated SUMOylation of SHP in maintaining BA homoeostasis and protecting from the BA hepatotoxicity. PMID:27412403

  7. CX3CL1, a chemokine finely tuned to adhesion: critical roles of the stalk glycosylation and the membrane domain

    Directory of Open Access Journals (Sweden)

    Mariano A. Ostuni

    2014-11-01

    Full Text Available The multi-domain CX3CL1 transmembrane chemokine triggers leukocyte adherence without rolling and migration by presenting its chemokine domain (CD to its receptor CX3CR1. Through the combination of functional adhesion assays with structural analysis using FRAP, we investigated the functional role of the other domains of CX3CL1, i.e., its mucin stalk, transmembrane domain, and cytosolic domain. Our results indicate that the CX3CL1 molecular structure is finely adapted to capture CX3CR1 in circulating cells and that each domain has a specific purpose: the mucin stalk is stiffened by its high glycosylation to present the CD away from the membrane, the transmembrane domain generates the permanent aggregation of an adequate amount of monomers to guarantee adhesion and prevent rolling, and the cytosolic domain ensures adhesive robustness by interacting with the cytoskeleton. We propose a model in which quasi-immobile CX3CL1 bundles are organized to quickly generate adhesive patches with sufficiently high strength to capture CX3CR1+ leukocytes but with sufficiently low strength to allow their patrolling behavior.

  8. Critical role of cyclooxygenase-2 activation in pathogenesis of hydronephrosis caused by lactational exposure of mice to dioxin

    International Nuclear Information System (INIS)

    Nishimura, Noriko; Matsumura, Fumio; Vogel, Christopher F.A.; Nishimura, Hisao; Yonemoto, Junzo; Yoshioka, Wataru; Tohyama, Chiharu

    2008-01-01

    Congenital hydronephrosis is a serious disease occurring among infants and children. Besides the intrinsic genetic factors, in utero exposure to a xenobiotic, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been suggested to induce hydronephrosis in rodents owing to anatomical obstruction in the ureter. Here, we report that hydronephrosis induced in mouse pups exposed lactationally to TCDD is not associated with anatomical obstruction, but with abnormal alterations in the subepithelial mesenchyma of the ureter. In the kidneys of these pups, the expressions of a battery of inflammatory cytokines including monocyte chemoattractant protein (MCP)-1, tumor necrosis factor α (TNFα) and interleukin (IL) -1β were up-regulated as early as postnatal day (PND) 7. The amounts of cyclooxygenase (COX) -2 mRNA and protein as well as prostaglandin E2 (PGE 2 ) were conspicuously up-regulated in an arylhydrocarbon-receptor-dependent manner in the TCDD-induced hydronephrotic kidney, with a subsequent down-regulation of the gene expressions of Na + and K + transporters, NKCC2 and ROMK. Daily administration of a COX-2 selective inhibitor to newborns until PND 7 completely abrogated the TCDD-induced PGE 2 synthesis and gene expressions of inflammatory cytokines and electrolyte transporters, and eventually prevented the onset of hydronephrosis. These findings suggest an essential role of COX-2 in mediating the TCDD action of inducing hydronephrosis through the functional impairment rather than the anatomical blockade of the ureter

  9. Critical role of developing national strategic plans as a guide to strengthen laboratory health systems in resource-poor settings.

    Science.gov (United States)

    Nkengasong, John N; Mesele, Tsehaynesh; Orloff, Sherry; Kebede, Yenew; Fonjungo, Peter N; Timperi, Ralph; Birx, Deborah

    2009-06-01

    Medical laboratory services are an essential, yet often neglected, component of health systems in developing countries. Their central role in public health, disease control and surveillance, and patient management is often poorly recognized by governments and donors. However, medical laboratory services in developing countries can be strengthened by leveraging funding from other sources of HIV/AIDS prevention, care, surveillance, and treatment programs. Strengthening these services will require coordinated efforts by national governments and partners and can be achieved by establishing and implementing national laboratory strategic plans and policies that integrate laboratory systems to combat major infectious diseases. These plans should take into account policy, legal, and regulatory frameworks; the administrative and technical management structure of the laboratories; human resources and retention strategies; laboratory quality management systems; monitoring and evaluation systems; procurement and maintenance of equipment; and laboratory infrastructure enhancement. Several countries have developed or are in the process of developing their laboratory plans, and others, such as Ethiopia, have implemented and evaluated their plan.

  10. Curcumin-Induced Apoptosis in Human Hepatocellular Carcinoma J5 Cells: Critical Role of Ca+2-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Wei-Hsun Wang

    2012-01-01

    Full Text Available The antitumor effects of curcumin, a natural biologically active compound extracted from rhizomes of Curcuma longa, have been studied in many cancer cell types including human hepatocellular carcinoma (HCC. Here, we investigated the effects of Ca2+ on curcumin-induced apoptosis in human HCC J5 cells. The abrogation of mitochondrial membrane potential (ΔΨm, the increase of reactive oxygen species (ROS production, and calcium release were demonstrated with flow cytometry as early as 15 minutes after curcumin treatment. In addition, an increase level of cytochrome c in the cytoplasm which led to DNA fragmentation was observed. To verify the role of Ca2+ in curcumin-induced apoptosis, 1,2-bis(o-aminophenoxyethane-N,N,N′,N′-tetraacetic acid (BAPTA, an intracellular calcium chelator, was applied. Cell viability was increased, but ΔΨm, ROS production, activation of caspase 3, and cell death were decreased in J5 cells pretreated with BAPTA for 2 h followed by the treatment of 25 μM curcumin. These results suggest that the curcumin-induced apoptosis in human HCC J5 cells is via mitochondria-dependent pathway and is closely related to the level of intracellular accumulation of calcium.

  11. The role of diagnostic imaging in the evaluation of suspected osteomyelitis in the foot: a critical review.

    Science.gov (United States)

    Harmer, James L; Pickard, James; Stinchcombe, Simon J

    2011-09-01

    The early diagnosis of osteomyelitis in the foot from its clinical presentation alone can be difficult particularly in cases when the early signs are subtle. Early diagnosis and subsequent early intervention are imperative to reduce the risk of chronic infection, associated early lytic changes to bone and potential long term structural complications caused by subsequent deformity and lost anatomy. Diagnostic imaging has a major role to play in the early assessment and diagnosis of bone infection, yet the choice of approach can be controversial. Several imaging modalities have been advocated, imaging of the infected foot is complex and no single test is ideal for every situation. The clinician needs to be aware of the strengths and weaknesses of each imaging modality so that the most appropriate test is selected for the individual case. Factors such as site of infection in the foot, the aggressive nature of the organism, the time since onset, previous associated surgery and co-morbidity may all play apart in the clinician's decision making process to determine the best approach in detecting the sometimes subtle changes which may be seen in some cases of osteomyelitis. This review considers the literature and highlights the advantages and disadvantages of the main imaging techniques used for the evaluation of the foot when osteomyelitis is suspected. An evidence based algorithm for the selection of appropriate imaging techniques is suggested to aid clinicians in there decision making process. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Critical roles of mucin-1 in sensitivity of lung cancer cells to tumor necrosis factor-alpha and dexamethasone.

    Science.gov (United States)

    Xu, Menglin; Wang, Xiangdong

    2017-08-01

    Lung cancer is the leading cause of death from cancer. Mucins are glycoproteins with high molecular weight, responsible for cell growth, differentiation, and signaling, and were proposed to be correlated with gene heterogeneity of lung cancer. Here, we report aberrant expression of mucin genes and tumor necrosis factor receptors in lung adenocarcinoma tissues compared with normal tissues in GEO datasets. Mucin-1 (MUC1) gene was selected and considered as the target gene; furthermore, the expression pattern of adenocarcinomic cells (A549, H1650, or H1299 cells) was validated under the stimulation with tumor necrosis factor-alpha (TNFα) or dexamethasone (DEX), separately. MUC1 gene interference was done to A549 cells to show its role in sensitivity of lung cancer cells to TNFα and DEX. Results of our experiments indicate that MUC1 may regulate the influence of inflammatory mediators in effects of glucocorticoids (GCs), as a regulatory target to improve therapeutics. It shows the potential effect of MUC1 and GCs in lung adenocarcinoma (LADC), which may help in LADC treatment in the future.

  13. Beneficial effects of vitamin C and vitamin E on reserpine-induced oral dyskinesia in rats: critical role of striatal catalase activity.

    Science.gov (United States)

    Faria, Rulian Ricardo; Abílio, Vanessa Costhek; Grassl, Christian; Chinen, Cibele Cristina; Negrão, Luciana Takahashi Ribeiro; de Castro, Juliana Pedroso Moraes Vilela; Fukushiro, Daniela Fukue; Rodrigues, Marcelo Scarpari Dutra; Gomes, Patricia Helena Zanier; Registro, Sibele; de Carvalho, Rita de Cassia; D'Almeida, Vania; Silva, Regina Helena; Ribeiro, Rosana de Alencar; Frussa-Filho, Roberto

    2005-06-01

    Oral dyskinesias are implicated in a series of neuropathologies and have been associated to an increase in oxidative stress. Several antioxidants, including vitamin E, decrease reserpine-induced oral dyskinesia (OD) in rodents and we have described a protective role of striatal catalase against the development of OD. The aim of this study was to verify the effects of vitamin C alone or in combination with vitamin E on reserpine-induced OD as well as to determine a possible role of catalase in the antidyskinetic property of these vitamins. Different doses of vitamin C attenuated reserpine-induced increase in OD. A similar treatment with an effective dose of vitamin C concomitant to an effective dose of vitamin E potentiated the antidyskinetic effect of both vitamins when administered alone. The administration of these vitamins alone produced an increase in striatal catalase activity that likewise was potentiated by their combined administration. In addition, the antidyskinetic property of vitamin E and vitamin C was abolished by a concomitant treatment with the catalase inhibitor aminotriazole. These results indicate a beneficial effect of these vitamins and reinforce the critical role of striatal catalase against the development of oral dyskinesias.

  14. SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells.

    Science.gov (United States)

    Rybak, Adrian P; Tang, Damu

    2013-12-01

    SOX2 is an essential transcription factor for stem cells and plays a role in tumorigenesis, however its role in prostate cancer stem cells (PCSCs) remains unclear. We report here a significant upregulation of SOX2 at both mRNA and protein levels in DU145 PCSCs propagated as suspension spheres in vitro. The expression of SOX2 in DU145 PCSCs is positively regulated by epidermal growth factor receptor (EGFR) signaling. Activation of EGFR signaling, following the addition of epidermal growth factor (EGF) or ectopic expression of a constitutively-active EGFR mutant (EGFRvIII), increased SOX2 expression and the self-renewal of DU145 PCSCs. Conversely, a small molecule EGFR inhibitor (AG1478) blocked EGFR activation, reduced SOX2 expression and inhibited PCSC self-renewal activity, implicating SOX2 in mediating EGFR-dependent self-renewal of PCSCs. In line with this notion, ectopic SOX2 expression enhanced EGF-induced self-renewal of DU145 PCSCs, while SOX2 knockdown reduced PCSC self-renewal with EGF treatment no longer capable of enhancing their propagation. Furthermore, SOX2 knockdown reduced the capacity of DU145 PCSCs to grow under anchorage-independent conditions. Finally, DU145 PCSCs generated xenograft tumors more aggressively with elevated levels of SOX2 expression compared to xenograft tumors derived from non-PCSCs. Collectively, we provide evidence that SOX2 plays a critical role in EGFR-mediated self-renewal of DU145 PCSCs. © 2013.

  15. Critical Role of Endoplasmic Reticulum Stress in Chronic Intermittent Hypoxia-Induced Deficits in Synaptic Plasticity and Long-Term Memory.

    Science.gov (United States)

    Xu, Lin-Hao; Xie, Hui; Shi, Zhi-Hui; Du, Li-Da; Wing, Yun-Kwok; Li, Albert M; Ke, Ya; Yung, Wing-Ho

    2015-09-20

    This study examined the role of endoplasmic reticulum (ER) stress in mediating chronic intermittent hypoxia (IH)-induced neurocognitive deficits. We designed experiments to demonstrate that ER stress is initiated in the hippocampus under chronic IH and determined its role in apoptotic cell death, impaired synaptic structure and plasticity, and memory deficits. Two weeks of IH disrupted ER fine structure and upregulated ER stress markers, glucose-regulated protein 78, caspase-12, and C/EBP homologous protein, in the hippocampus, which could be suppressed by ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid. Meanwhile, ER stress induced apoptosis via decreased Bcl-2, promoted reactive oxygen species production, and increased malondialdehyde formation and protein carbonyl, as well as suppressed mitochondrial function. These effects were largely prevented by ER stress inhibitors. On the other hand, suppression of oxidative stress could reduce ER stress. In addition, the length of the synaptic active zone and number of mature spines were reduced by IH. Long-term recognition memory and spatial memory were also impaired, which was accompanied by reduced long-term potentiation in the Schaffer collateral pathway. These effects were prevented by coadministration of the TUDCA. These results show that ER stress plays a critical role in underlying memory deficits in obstructive sleep apnea (OSA)-associated IH. Attenuators of ER stress may serve as novel adjunct therapeutic agents for ameliorating OSA-induced neurocognitive impairment.

  16. Critical Role of Interdomain Interactions in the Conformational Change and Catalytic Mechanism of Endoplasmic Reticulum Aminopeptidase 1.

    Science.gov (United States)

    Stamogiannos, Athanasios; Maben, Zachary; Papakyriakou, Athanasios; Mpakali, Anastasia; Kokkala, Paraskevi; Georgiadis, Dimitris; Stern, Lawrence J; Stratikos, Efstratios

    2017-03-14

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an intracellular enzyme that is important for the generation of antigenic epitopes and major histocompatibility class I-restricted adaptive immune responses. ERAP1 processes a vast variety of different peptides but still shows length and sequence selectivity, although the mechanism behind these properties is poorly understood. X-ray crystallographic analysis has revealed that ERAP1 can assume at least two distinct conformations in which C-terminal domain IV is either proximal or distal to active site domain II. To improve our understanding of the role of this conformational change in the catalytic mechanism of ERAP1, we used site-directed mutagenesis to perturb key salt bridges between domains II and IV. Enzymatic analysis revealed that these mutations, although located away from the catalytic site, greatly reduce the catalytic efficiency and change the allosteric kinetic behavior. The variants were more efficiently activated by small peptides and bound a competitive inhibitor with weaker affinity and faster dissociation kinetics. Molecular dynamics analysis suggested that the mutations affect the conformational distribution of ERAP1, reducing the population of closed states. Small-angle X-ray scattering indicated that both the wild type and the ERAP1 variants are predominantly in an open conformational state in solution. Overall, our findings suggest that electrostatic interactions between domains II and IV in ERAP1 are crucial for driving a conformational change that regulates the structural integrity of the catalytic site. The extent of domain opening in ERAP1 probably underlies its specialization for antigenic peptide precursors and should be taken into account in inhibitor development efforts.

  17. JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Yung-Ting Kuo

    Full Text Available Neuroblastoma (NB is a common neural crest-derived extracranial solid cancer in children. Among all childhood cancers, NB causes devastating loss of young lives as it accounts for 15% of childhood cancer mortality. Neuroblastoma, especially high-risk stage 4 NB with MYCN amplification has limited treatment options and associated with poor prognosis. This necessitates the need for novel effective therapeutic strategy. JARID1B, also known as KDM5B, is a histone lysine demethylase, identified as an oncogene in many cancer types. Clinical data obtained from freely-accessible databases show a negative correlation between JARID1B expression and survival rates. Here, we demonstrated for the first time the role of JARID1B in the enhancement of stem cell-like activities and drug resistance in NB cells. We showed that JARID1B may be overexpressed in either MYCN amplification (SK-N-BE(2 or MYCN-non-amplified (SK-N-SH and SK-N-FI cell lines. JARID1B expression was found enriched in tumor spheres of SK-N-BE(2 and SK-N-DZ. Moreover, SK-N-BE(2 spheroids were more resistant to chemotherapeutics as compared to parental cells. In addition, we demonstrated that JARID1B-silenced cells acquired a decreased propensity for tumor invasion and tumorsphere formation, but increased sensitivity to cisplatin treatment. Mechanistically, reduced JARID1B expression led to the downregulation of Notch/Jagged signaling. Collectively, we provided evidence that JARID1B via modulation of stemness-related signaling is a putative novel therapeutic target for treating malignant NB.

  18. Critical role of mitochondrial ROS is dependent on their site of production on the electron transport chain in ischemic heart.

    Science.gov (United States)

    Madungwe, Ngonidzashe B; Zilberstein, Netanel F; Feng, Yansheng; Bopassa, Jean C

    2016-01-01

    Reactive oxygen species (ROS) generation has been implicated in many pathologies including ischemia/reperfusion (I/R) injury. This led to multiple studies on antioxidant therapies to treat cardiovascular diseases but paradoxically, results have so far been mixed as ROS production can be beneficial as a signaling mechanism and in cardiac protection via preconditioning interventions. We investigated whether the differential impact of increased ROS in injury as well as in protection could be explained by their site of production on the mitochondrial electron transport chain. Using amplex red to measure ROS production, we found that mitochondria isolated from hearts after I/R produced more ROS than non-ischemic when complex I substrate (glutamate/malate) was used. Interestingly, the substrates of complex II (succinate) and ubiquinone (sn-glycerol 3-phosphate, G3P) produced less ROS in mitochondria from I/R hearts compared to normal healthy hearts. The inhibitors of complex I (rotenone) and complex III (antimycin A) increased ROS production when glutamate/malate and G3P were used; in contrast, they reduced ROS production when the complex II substrate was used. Mitochondrial calcium retention capacity required to induce mitochondrial permeability transition pore (mPTP) opening was measured using calcium green fluorescence and was found to be higher when mitochondria were treated with G3P and succinate compared to glutamate/malate. Furthermore, Langendorff hearts treated with glutamate/malate exhibited reduced cardiac functional recovery and increased myocardial infarct size compared to hearts treated with G3P. Thus, ROS production by the stimulated respiratory chain complexes I and III has opposite roles: cardio-deleterious when produced in complex I and cardio-protective when produced in complex III. The mechanism of these ROS involves the inhibition of the mPTP opening, a key event in cell death following ischemia/reperfusion injury.

  19. Critical role of p53 upregulated modulator of apoptosis in benzyl isothiocyanate-induced apoptotic cell death.

    Directory of Open Access Journals (Sweden)

    Marie Lue Antony

    Full Text Available Benzyl isothiocyanate (BITC, a constituent of edible cruciferous vegetables, decreases viability of cancer cells by causing apoptosis but the mechanism of cell death is not fully understood. The present study was undertaken to determine the role of Bcl-2 family proteins in BITC-induced apoptosis using MDA-MB-231 (breast, MCF-7 (breast, and HCT-116 (colon human cancer cells. The B-cell lymphoma 2 interacting mediator of cell death (Bim protein was dispensable for proapoptotic response to BITC in MCF-7 and MDA-MB-231 cells as judged by RNA interference studies. Instead, the BITC-treated MCF-7 and MDA-MB-231 cells exhibited upregulation of p53 upregulated modulator of apoptosis (PUMA protein. The BITC-mediated induction of PUMA was relatively more pronounced in MCF-7 cells due to the presence of wild-type p53 compared with MDA-MB-231 with mutant p53. The BITC-induced apoptosis was partially but significantly attenuated by RNA interference of PUMA in MCF-7 cells. The PUMA knockout variant of HCT-116 cells exhibited significant resistance towards BITC-induced apoptosis compared with wild-type HCT-116 cells. Attenuation of BITC-induced apoptosis in PUMA knockout HCT-116 cells was accompanied by enhanced G2/M phase cell cycle arrest due to induction of p21 and down regulation of cyclin-dependent kinase 1 protein. The BITC treatment caused a decrease in protein levels of Bcl-xL (MCF-7 and MDA-MB-231 cells and Bcl-2 (MCF-7 cells. Ectopic expression of Bcl-xL in MCF-7 and MDA-MB-231 cells and that of Bcl-2 in MCF-7 cells conferred protection against proapoptotic response to BITC. Interestingly, the BITC-treated MDA-MB-231 cells exhibited induction of Bcl-2 protein expression, and RNA interference of Bcl-2 in this cell line resulted in augmentation of BITC-induced apoptosis. The BITC-mediated inhibition of MDA-MB-231 xenograft growth in vivo was associated with the induction of PUMA protein in the tumor. In conclusion, the results of the present study

  20. Hypoxia inducible factor 3α plays a critical role in alveolarization and distal epithelial cell differentiation during mouse lung development.

    Directory of Open Access Journals (Sweden)

    Yadi Huang

    Full Text Available Lung development occurs under relative hypoxia and the most important oxygen-sensitive response pathway is driven by Hypoxia Inducible Factors (HIF. HIFs are heterodimeric transcription factors of an oxygen-sensitive subunit, HIFα, and a constitutively expressed subunit, HIF1β. HIF1α and HIF2α, encoded by two separate genes, contribute to the activation of hypoxia inducible genes. A third HIFα gene, HIF3α, is subject to alternative promoter usage and splicing, leading to three major isoforms, HIF3α, NEPAS and IPAS. HIF3α gene products add to the complexity of the hypoxia response as they function as dominant negative inhibitors (IPAS or weak transcriptional activators (HIF3α/NEPAS. Previously, we and others have shown the importance of the Hif1α and Hif2α factors in lung development, and here we investigated the role of Hif3α during pulmonary development. Therefore, HIF3α was conditionally expressed in airway epithelial cells during gestation and although HIF3α transgenic mice were born alive and appeared normal, their lungs showed clear abnormalities, including a post-pseudoglandular branching defect and a decreased number of alveoli. The HIF3α expressing lungs displayed reduced numbers of Clara cells, alveolar epithelial type I and type II cells. As a result of HIF3α expression, the level of Hif2α was reduced, but that of Hif1α was not affected. Two regulatory genes, Rarβ, involved in alveologenesis, and Foxp2, a transcriptional repressor of the Clara cell specific Ccsp gene, were significantly upregulated in the HIF3α expressing lungs. In addition, aberrant basal cells were observed distally as determined by the expression of Sox2 and p63. We show that Hif3α binds a conserved HRE site in the Sox2 promoter and weakly transactivated a reporter construct containing the Sox2 promoter region. Moreover, Hif3α affected the expression of genes not typically involved in the hypoxia response, providing evidence for a novel

  1. A Critical Role of the PTEN/PDGF Signaling Network for the Regulation of Radiosensitivity in Adenocarcinoma of the Prostate

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, Michael, E-mail: mechristense@uwalumni.com [Department of Radiation Oncology, Wayne State University School of Medicine, Barbara Ann Karmanos Cancer Center, Detroit, Michigan (United States); Najy, Abdo J. [Department of Pathology, Wayne State University School of Medicine, Barbara Ann Karmanos Cancer Center, Detroit, Michigan (United States); Snyder, Michael; Movilla, Lisa S. [Department of Radiation Oncology, Wayne State University School of Medicine, Barbara Ann Karmanos Cancer Center, Detroit, Michigan (United States); Kim, Hyeong-Reh Choi [Department of Pathology, Wayne State University School of Medicine, Barbara Ann Karmanos Cancer Center, Detroit, Michigan (United States)

    2014-01-01

    Purpose: Loss or mutation of the phosphate and tensin homologue (PTEN) is a common genetic abnormality in prostate cancer (PCa) and induces platelet-derived growth factor D (PDGF D) signaling. We examined the role of the PTEN/PDGF axis on radioresponse using a murine PTEN null prostate epithelial cell model. Methods and Materials: PTEN wild-type (PTEN{sup +/+}) and PTEN knockout (PTEN{sup −/−}) murine prostate epithelial cell lines were used to examine the relationship between the PTEN status and radiosensitivity and also to modulate the PDGF D expression levels. PTEN{sup −/−} cells were transduced with a small hairpin RNA (shRNA) lentiviral vector containing either scrambled nucleotides (SCRM) or sequences targeted to PDGF D (shPDGF D). Tumorigenesis and morphogenesis of these cell lines were evaluated in vivo via subcutaneous injection of male nude mice and in vitro using Matrigel 3-dimensional (3D) culture. Effects of irradiation on clonogenic survival, cell migration, and invasion were measured with respect to the PTEN status and the PDGF D expression level. In addition, apoptosis and cell cycle redistribution were examined as potential mechanisms for differences seen. Results: PTEN{sup −/−} cells were highly tumorigenic in animals and effectively formed foci in 3D culture. Importantly, loss of PDGF D in these cell lines drastically diminished these phenotypes. Furthermore, PTEN{sup −/−} cells demonstrated increased clonogenic survival in vitro compared to PTEN{sup +/+}, and attenuation of PDGF D significantly reversed this radioresistant phenotype. PTEN{sup −/−} cells displayed greater migratory and invasive potential at baseline as well as after irradiation. Both the basal and radiation-induced migratory and invasive phenotypes in PTEN{sup −/−} cells required PDGF D expression. Interestingly, these differences were independent of apoptosis and cell cycle redistribution, as they showed no significant difference. Conclusions: We propose

  2. Immuno-PET Imaging of HER3 in a Model in which HER3 Signaling Plays a Critical Role.

    Directory of Open Access Journals (Sweden)

    Qinghua Yuan

    Full Text Available HER3 is overexpressed in various carcinomas including colorectal cancer (CRC, which is associated with poor prognosis, and is involved in the development of therapy resistance. Thus, an in vivo imaging technique is needed to evaluate the expression of HER3, an important therapeutic and diagnostic target. Here, we report successful HER3 PET imaging using a newly generated anti-human HER3 monoclonal antibody, Mab#58, and a mouse model of a HER3-overexpressing xenograft tumor. Furthermore, we assessed the role of HER3 signaling in CRC cancer tissue-originated spheroid (CTOS and applied HER3 imaging to detect endogenous HER3 in CTOS-derived xenografts. Cell binding assays of 89Zr-labeled Mab#58 using the HER3-overexpressing cell line HER3/RH7777 demonstrated that [89Zr]Mab#58 specifically bound to HER3/RH7777 cells (Kd = 2.7 nM. In vivo biodistribution study in mice bearing HER3/RH7777 and its parent cell xenografts showed that tumor accumulation of [89Zr]Mab#58 in HER3/RH7777 xenografts was significantly higher than that in the control from day 1 to day 4, tending to increase from day 1 to day 4 and reaching 12.2 ± 4.5%ID/g. Radioactivity in other tissues, including the control xenograft, decreased or remained unchanged from day 1 to day 6. Positron emission tomography (PET in the same model enabled clear visualization of HER3/RH7777 xenografts but not of RH7777 xenografts. CTOS growth assay and signaling assay revealed that CRC CTOS were dependent on HER3 signaling for their growth. In PET studies of mice bearing a CRC CTOS xenograft, the tumor was clearly visualized with [89Zr]Mab#58 but not with the 89Zr-labeled control antibody. Thus, tumor expression of HER3 was successfully visualized by PET with 89Zr-labeled anti-HER3 antibody in CTOS xenograft-bearing mice, a model that retains the properties of the patient tumor. Non-invasive targeting of HER3 by antibodies is feasible, and it is expected to be useful for cancer diagnosis and treatment.

  3. Critical role of glycogen synthase kinase-3β in regulating the avian heterophil response to Salmonella enterica serovar Enteritidis

    Directory of Open Access Journals (Sweden)

    Michael eKogut

    2014-11-01

    Full Text Available A microarray-assisted gene expression screen of chicken heterophils revealed glycogen synthase kinase-3β (GSK-3β, a multifunctional Ser/Thr kinase, to be consistently up-regulated 30-180 min following stimulation with Salmonella enterica serovar Enteritidis (S. Enteritidis. The present study was designed to delineate the role of GSK-3β in regulating the innate function of chicken heterophils in response to S. Enteritidis exposure. Using a specific GSK-3β ELISA assay, 30 min after infection with S. Enteritidis, heterophils had a significant decrease in total GSK-3β, but a significant increase in phosphorylated GSK-3 (Ser9. By 60 min post-infection, there was no difference in the amount of phosphorylated GSK-3β (Ser9 in either the uninfected and infected heterophils. S. Enteritidis interaction with heterophils alters GSK-3 activity by stimulating phosphorylation at Ser9 and that peaks by 30 min post-infection. Further, inhibition of GSK3β with lithium chloride resulted in a significant decrease in NF-κB activation and expression of IL-6, but induces a significant increase in the expression of the anti-inflammatory cytokine, IL-10. Using a phospho-specific antibody array confirmed the phosphorylation of GSK-3β (Ser9 as well as the phosphorylation of the downstream cytokine-activated intracellular signaling pathway involved in stimulating immune responses, IκB, the IκB subunit IKK-β, and the NF-κB subunits p105, p65, and c-Rel. Our data revealed that the phosphorylation of GSK-3β (Ser9 is responsible for inducing and controlling an innate response to the bacteria. Our findings suggest that the repression of GSK-3 activity is beneficial to the host cell and may act as a target for treatment in controlling intestinal colonization in chickens. Further experiments will define the in vivo modulation of GSK-3 as a potential alternative to antibiotics in salmonella and other intestinal bacterial infections.

  4. The Role of Slope in the Fill and Spill Process of Linked Submarine Minibasins. Model Validation and Numerical Runs at Laboratory Scale.

    Science.gov (United States)

    Bastianon, E.; Viparelli, E.; Cantelli, A.; Imran, J.

    2015-12-01

    Primarily motivated by applications to hydrocarbon exploration, submarine minibasins have been widely studied during recent decades to understand the physical phenomenon that characterizes their fill process. Minibasins were identified in seismic records in the Gulf of Mexico, Angola, Trinidad and Tobago, Ireland, Nigeria and also in outcrops (e.g., Tres Pasos Formation, southern Chile). The filling of minibasis is generally described as the 'fill-and-spill' process, i.e. turbidity currents enter, are reflected on the minibasin flanks, pond and deposit suspended sediment. As the minibasin fills the turbidity current spills on the lowermost zone of the basin flank -spill point - and start filling the next basin downdip. Different versions of this simplified model were used to interpret field and laboratory data but it is still unclear how the minibasin size compared to the magnitude of the turbidity currents, the position of each basin in the system, and the slope of the minibasin system affects the characteristics of the deposit (e.g., geometry, grain size). Here, we conduct a numerical study to investigate how the 'fill-and-spill' model changes with increase in slopes of the minibasin system. First, we validate our numerical results against laboratory experiment performed on two linked minibasins located on a horizontal platform by comparing measured and simulated deposit geometries, suspended sediment concentration profiles and grain sizes. We then perform numerical simulations by increasing the minibasin system slope: deposit and flow characteristics are compared with the case of horizontal platform to identify how the depositional processes change. For the numerical study we used a three-dimensional numerical model of turbidity currents that solves the Reynolds-averaged Navier-Stokes equations for dilute suspensions. Turbulence is modeled by a buoyancy-modified k-ɛ closure. The numerical model has a deforming bottom boundary, to model the changes in the bed

  5. Critical Axial Load

    Directory of Open Access Journals (Sweden)

    Walt Wells

    2008-01-01

    Full Text Available Our objective in this paper is to solve a second order differential equation for a long, simply supported column member subjected to a lateral axial load using Heun's numerical method. We will use the solution to find the critical load at which the column member will fail due to buckling. We will calculate this load using Euler's derived analytical approach for an exact solution, as well as Euler's Numerical Method. We will then compare the three calculated values to see how much they deviate from one another. During the critical load calculation, it will be necessary to calculate the moment of inertia for the column member.

  6. Early Retinal Defects in Fmr1−/y Mice: Toward a Critical Role of Visual Dys-Sensitivity in the Fragile X Syndrome Phenotype?

    Directory of Open Access Journals (Sweden)

    Olivier Perche

    2018-04-01

    Full Text Available Fragile X Syndrome (FXS is caused by a deficiency in Fragile X Mental Retardation Protein (FMRP leading to global sensorial abnormalities, among which visual defects represent a critical part. These visual defects are associated with cerebral neuron immaturity especially in the primary visual cortex. However, we recently demonstrated that retinas of adult Fmr1−/y mice, the FXS murine model, present molecular, cellular and functional alterations. However, no data are currently available on the evolution pattern of such defects. As retinal stimulation through Eye Opening (EO is a crucial signal for the cerebral visual system maturation, we questioned the precocity of molecular and functional retinal phenotype. To answer this question, we studied the retinal molecular phenotype of Fmr1−/y mice before EO until adult age and the consequences of the retinal loss of Fmrp on retinal function in young and adult mice. We showed that retinal molecular defects are present before EO and remain stable at adult age, leading to electrophysiological impairments without any underlying structural changes. We underlined that loss of Fmrp leads to a wide range of defects in the retina, settled even before EO. Our work demonstrates a critical role of the sensorial dysfunction in the Fmr1−/y mice overall phenotype, and provides evidence that altered peripheral perception is a component of the sensory processing defect in FXS conditions.

  7. Early Retinal Defects in Fmr1-/y Mice: Toward a Critical Role of Visual Dys-Sensitivity in the Fragile X Syndrome Phenotype?

    Science.gov (United States)

    Perche, Olivier; Felgerolle, Chloé; Ardourel, Maryvonne; Bazinet, Audrey; Pâris, Arnaud; Rossignol, Rafaëlle; Meyer-Dilhet, Géraldine; Mausset-Bonnefont, Anne-Laure; Hébert, Betty; Laurenceau, David; Montécot-Dubourg, Céline; Menuet, Arnaud; Bizot, Jean-Charles; Pichon, Jacques; Ranchon-Cole, Isabelle; Briault, Sylvain

    2018-01-01

    Fragile X Syndrome (FXS) is caused by a deficiency in Fragile X Mental Retardation Protein (FMRP) leading to global sensorial abnormalities, among which visual defects represent a critical part. These visual defects are associated with cerebral neuron immaturity especially in the primary visual cortex. However, we recently demonstrated that retinas of adult Fmr1 -/y mice, the FXS murine model, present molecular, cellular and functional alterations. However, no data are currently available on the evolution pattern of such defects. As retinal stimulation through Eye Opening (EO) is a crucial signal for the cerebral visual system maturation, we questioned the precocity of molecular and functional retinal phenotype. To answer this question, we studied the retinal molecular phenotype of Fmr1 -/y mice before EO until adult age and the consequences of the retinal loss of Fmrp on retinal function in young and adult mice. We showed that retinal molecular defects are present before EO and remain stable at adult age, leading to electrophysiological impairments without any underlying structural changes. We underlined that loss of Fmrp leads to a wide range of defects in the retina, settled even before EO. Our work demonstrates a critical role of the sensorial dysfunction in the Fmr1 -/y mice overall phenotype, and provides evidence that altered peripheral perception is a component of the sensory processing defect in FXS conditions.

  8. Early Retinal Defects in Fmr1−/y Mice: Toward a Critical Role of Visual Dys-Sensitivity in the Fragile X Syndrome Phenotype?

    Science.gov (United States)

    Perche, Olivier; Felgerolle, Chloé; Ardourel, Maryvonne; Bazinet, Audrey; Pâris, Arnaud; Rossignol, Rafaëlle; Meyer-Dilhet, Géraldine; Mausset-Bonnefont, Anne-Laure; Hébert, Betty; Laurenceau, David; Montécot-Dubourg, Céline; Menuet, Arnaud; Bizot, Jean-Charles; Pichon, Jacques; Ranchon-Cole, Isabelle; Briault, Sylvain

    2018-01-01

    Fragile X Syndrome (FXS) is caused by a deficiency in Fragile X Mental Retardation Protein (FMRP) leading to global sensorial abnormalities, among which visual defects represent a critical part. These visual defects are associated with cerebral neuron immaturity especially in the primary visual cortex. However, we recently demonstrated that retinas of adult Fmr1−/y mice, the FXS murine model, present molecular, cellular and functional alterations. However, no data are currently available on the evolution pattern of such defects. As retinal stimulation through Eye Opening (EO) is a crucial signal for the cerebral visual system maturation, we questioned the precocity of molecular and functional retinal phenotype. To answer this question, we studied the retinal molecular phenotype of Fmr1−/y mice before EO until adult age and the consequences of the retinal loss of Fmrp on retinal function in young and adult mice. We showed that retinal molecular defects are present before EO and remain stable at adult age, leading to electrophysiological impairments without any underlying structural changes. We underlined that loss of Fmrp leads to a wide range of defects in the retina, settled even before EO. Our work demonstrates a critical role of the sensorial dysfunction in the Fmr1−/y mice overall phenotype, and provides evidence that altered peripheral perception is a component of the sensory processing defect in FXS conditions. PMID:29681800

  9. Critical role of γ4 chain in the expression of functional Vγ4Vδ1 T cell receptor of gastric tumour-infiltrating γδT lymphocytes.

    Science.gov (United States)

    Jiang, Y; Tang, F; Li, Z; Cui, L; He, W

    2012-01-01

    Vγ4Vδ1 T cell receptor (TCRγ4δ1)-expressing γδT cells were the most dominant subset in gastric tumour-infiltrating γδT cells (γδTIL) we recently analyzed. To study the essential roles of γ and δ chains in assembly and function of TCRγ4δ1, we sequenced and constructed them into lentiviral vectors for the reconstitution of TCRγ4δ1 using different modalities of transduction. We were able to efficiently reconstitute TCRγ4δ1 with functional activities when both γ4 and δ1 chains are coexpressed in TCR-negative J.RT3-T3.5 cells. However, the expression of δ1 chain is greatly diminished when γ4 expression is absent, suggesting that the coexpressing γ4 is critical in maintaining the folding and stability of δ1 product. To functionally study the reconstituted TCRγ4δ1, we examined the cytolytic activity of TCRγ4δ1-reconstituted J.RT3-T3.5 cells and cytokine secretion and found the receptors are fully functional, but their functionality also requires the presence of γ4. Our results demonstrated that γ4 is critical for the stability of δ1 and the function of TCRγ4δ1. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

  10. Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice.

    Science.gov (United States)

    Lim, Joohyun; Burclaff, Joseph; He, Guangxu; Mills, Jason C; Long, Fanxin

    2017-01-01

    Cre/loxP technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of Cre expression. The Dmp1-Cre mouse, expressing Cre from a 14-kb DNA fragment of the mouse Dmp1 gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the Ai9 reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice, Dmp1-Cre targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction. In the bone marrow, Cre activity is evident in certain stromal cells adjacent to the blood vessels, but not in adipocytes. Outside the skeleton, Dmp1-Cre marks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that express Pdgfra . Confirming the utility of Dmp1-Cre in the gastrointestinal mesenchyme, deletion of Bmpr1a with Dmp1-Cre causes numerous large polyps along the gastrointestinal tract, consistent with prior work involving inhibition of BMP signaling. Thus, caution needs to be exercised when using Dmp1-Cre because it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types.

  11. A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA.

    Science.gov (United States)

    Aljurayyan, A N; Sharma, R; Upile, N; Beer, H; Vaughan, C; Xie, C; Achar, P; Ahmed, M S; McNamara, P S; Gordon, S B; Zhang, Q

    2016-08-01

    T Follicular helper cells (TFH) are considered critical for B cell antibody response, and recent efforts have focused on promoting TFH in order to enhance vaccine efficacy. We studied the frequency and function of TFH in nasopharynx-associated lymphoid tissues (NALT) from children and adults, and its role in anti-influenza antibody response following stimulation by a live-attenuated influenza vaccine (LAIV) or an inactivated seasonal virus antigen (sH1N1). We further studied whether CpG-DNA promotes TFH and by which enhances anti-influenza response. We showed NALT from children aged 1.5-10 years contained abundant TFH, suggesting efficient priming of TFH during early childhood. Stimulation by LAIV induced a marked increase in TFH that correlated with a strong production of anti-hemagglutinin (HA) IgA/IgG/IgM antibodies in tonsillar cells. Stimulation by the inactivated sH1N1 antigen induced a small increase in TFH which was markedly enhanced by CpG-DNA, accompanied by enhanced anti-HA antibody responses. In B cell co-culture experiment, anti-HA responses were only seen in the presence of TFH, and addition of plasmacytoid dendritic cell to TFH-B cell co-culture enhanced the TFH-mediated antibody production following CpG-DNA and sH1N1 antigen stimulation. Induction of TFH differentiation from naïve T cells was also shown following the stimulation. Our results support a critical role of TFH in human mucosal anti-influenza antibody response. Use of an adjuvant such as CpG-DNA that has the capacity to promote TFH by which to enhance antigen-induced antibody responses in NALT tissue may have important implications for future vaccination strategies against respiratory pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Role of Slip Velocity in a Magneto-Micropolar Fluid Flow from a Radiative Surface with Variable Permeability: A Numerical Study

    Directory of Open Access Journals (Sweden)

    Sharma B.K.

    2017-08-01

    Full Text Available An analysis is presented to describe the hydromagnetic mixed convection flow of an electrically conducting micropolar fluid past a vertical plate through a porous medium with radiation and slip flow regime. A uniform magnetic field has been considered in the study which absorbs the micropolar fluid with a varying suction velocity and acts perpendicular to the porous surface of the above plate. The governing non-linear partial differential equations have been transformed into linear partial differential equations, which are solved numerically by applying the explicit finite difference method. The numerical results are presented graphically in the form of velocity, micro-rotation, concentration and temperature profiles, the skin-friction coefficient, the couple stress coefficient, the rate of heat and mass transfers at the wall for different material parameters.

  13. Penetrator strength effect in long-rod critical ricochet angle

    International Nuclear Information System (INIS)

    Daneshjou, K.; Shahravi, M.

    2008-01-01

    3D numerical simulations were performed in order to further investigate the role of penetrator strength in the interaction of long-rods and oblique targets. Three distinctive regimes resulting from oblique impact depending on the obliquity, namely simple ricochet, critical ricochet and target perforation, were investigated in detail. Critical ricochet angles were calculated with a full 3D explicit finite element method for various impact velocities and strength of target plates and projectiles. Numerical predictions were compared with existing two-dimensional analytical models and test results. It was predicted that critical ricochet angle increases with decreasing impact velocity and that higher ricochet angles were expected if higher strength target materials are employed. But there are differences between analytical models and 3D numerical simulation results or test results. The causes for these discrepancies are established by numerical simulations which explore the validity of the penetrator strength parameter in the analytical model as a physical entity. As a matter of fact, in this paper we first investigate the role of penetrator dynamic strength using two-dimensional simulation which resulted in different penetrator strengths out of different impact velocities. Next, by applying these amounts for penetrator strength in Rosenberg analytical model the critical ricochet angle is calculated. Finally, a comparison between the present analytical method with the 3D simulation and test results shows that the new analytical approach leads to modified results with respect to Rosenberg ones

  14. Numerical models of salt diapir formation by down-building : the role of sedimentation rate, viscosity contrast, initial amplitude and wavelength

    OpenAIRE

    Fuchs, Lukas; Schmeling, H.; Koyi, Hemin

    2011-01-01

    Formation of salt diapirs has been described to be due to upbuilding (i. e. Rayleigh-Taylor like instability of salt diapirs piercing through a denser sedimentary overburden) or syndepositional down-building process (i. e. the top of the salt diapir remains at the surface all the time). Here we systematically analyse this second end-member mechanism by numerical modelling. Four parameters are varied: sedimentation rate nu(sed), salt viscosity eta(salt), amplitude delta of the initial perturba...

  15. Development of numerical concepts

    Directory of Open Access Journals (Sweden)

    Sabine Peucker

    2013-06-01

    Full Text Available The development of numerical concepts is described from infancy to preschool age. Infants a few days old exhibit an early sensitivity for numerosities. In the course of development, nonverbal mental models allow for the exact representation of small quantities as well as changes in these quantities. Subitising, as the accurate recognition of small numerosities (without counting, plays an important role. It can be assumed that numerical concepts and procedures start with insights about small numerosities. Protoquantitative schemata comprise fundamental knowledge about quantities. One-to-one-correspondence connects elements and numbers, and, for this reason, both quantitative and numerical knowledge. If children understand that they can determine the numerosity of a collection of elements by enumerating the elements, they have acquired the concept of cardinality. Protoquantitative knowledge becomes quantitative if it can be applied to numerosities and sequential numbers. The concepts of cardinality and part-part-whole are key to numerical development. Developmentally appropriate learning and teaching should focus on cardinality and part-part-whole concepts.

  16. Critical role of non-muscle myosin light chain kinase in thrombin-induced endothelial cell inflammation and lung PMN infiltration.

    Science.gov (United States)

    Fazal, Fabeha; Bijli, Kaiser M; Murrill, Matthew; Leonard, Antony; Minhajuddin, Mohammad; Anwar, Khandaker N; Finkelstein, Jacob N; Watterson, D Martin; Rahman, Arshad

    2013-01-01

    The pathogenesis of acute lung injury (ALI) involves bidirectional cooperation and close interaction between inflammatory and coagulation pathways. A key molecule linking coagulation and inflammation is the procoagulant thrombin, a serine protease whose concentration is elevated in plasma and lavage fluids of patients with ALI and acute respiratory distress syndrome (ARDS). However, little is known about the mechanism by which thrombin contributes to lung inflammatory response. In this study, we developed a new mouse model that permits investigation of lung inflammation associated with intravascular coagulation. Using this mouse model and in vitro approaches, we addressed the role of non-muscle myosin light chain kinase (nmMLCK) in thrombin-induced endothelial cell (EC) inflammation and lung neutrophil (PMN) infiltration. Our in vitro experiments revealed a key role of nmMLCK in ICAM-1 expression by its ability to control nuclear translocation and transcriptional capacity of RelA/p65 in EC. When subjected to intraperitoneal thrombin challenge, wild type mice showed a marked increase in lung PMN infiltration via expression of ICAM-1. However, these responses were markedly attenuated in mice deficient in nmMLCK. These results provide mechanistic insight into lung inflammatory response associated with intravascular coagulation and identify nmMLCK as a critical target for modulation of lung inflammation.

  17. Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells.

    Science.gov (United States)

    Yao, Takako; Fujimura, Tsutomu; Murayama, Kimie; Okumura, Ko; Seko, Yoshinori

    2017-10-18

    We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo. In this study, to investigate the mechanism of cell injury of cardiac myocytes and pancreatic β-cells involved in diabetes mellitus (DM), we analyzed plasma ORAIP levels in DM model rats and the role of ORAIP in high glucose-induced apoptosis of cardiac myocytes in vitro. We also examined whether recombinant-ORAIP induces apoptosis in pancreatic β-cells. Plasma ORAIP levels in DM rats during diabetic phase were about 18 times elevated as compared with non-diabetic phase. High glucose induced massive apoptosis in cardiac myocytes (66.2 ± 2.2%), which was 78% suppressed by neutralizing anti-ORAIP mAb in vitro. Furthermore, recombinant-ORAIP clearly induced apoptosis in pancreatic β-cells in vitro. These findings strongly suggested that ORAIP plays a pivotal role in hyperglycemia-induced myocardial injury and pancreatic β-cell injury in DM. ORAIP will be a biomarker and a critical therapeutic target for cardiac injury and progression of DM itself.

  18. CCR4-Not Complex Subunit Not2 Plays Critical Roles in Vegetative Growth, Conidiation and Virulence in Watermelon Fusarium Wilt Pathogen Fusarium oxysporum f. sp. niveum

    Science.gov (United States)

    Dai, Yi; Cao, Zhongye; Huang, Lihong; Liu, Shixia; Shen, Zhihui; Wang, Yuyan; Wang, Hui; Zhang, Huijuan; Li, Dayong; Song, Fengming

    2016-01-01

    CCR4-Not complex is a multifunctional regulator that plays important roles in multiple cellular processes in eukaryotes. In the present study, the biological function of FonNot2, a core subunit of the CCR4-Not complex, was explored in Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon wilt disease. FonNot2 was expressed at higher levels in conidia and germinating conidia and during infection in Fon-inoculated watermelon roots than in mycelia. Targeted disruption of FonNot2 resulted in retarded vegetative growth, reduced conidia production, abnormal conidial morphology, and reduced virulence on watermelon. Scanning electron microscopy observation of infection behaviors and qRT-PCR analysis of in planta fungal growth revealed that the ΔFonNot2 mutant was defective in the ability to penetrate watermelon roots and showed reduced fungal biomass in root and stem of the inoculated plants. Phenotypic and biochemical analyses indicated that the ΔFonNot2 mutant displayed hypersensitivity to cell wall perturbing agents (e.g., Congo Red and Calcofluor White) and oxidative stress (e.g., H2O2 and paraquat), decreased fusaric acid content, and reduced reactive oxygen species (ROS) production during spore germination. Our data demonstrate that FonNot2 plays critical roles in regulating vegetable growth, conidiogenesis and conidia morphology, and virulence on watermelon via modulating cell wall integrity, oxidative stress response, ROS production and FA biosynthesis through the regulation of transcription of genes involved in multiple pathways. PMID:27695445

  19. Ferrofluids: Modeling, numerical analysis, and scientific computation

    Science.gov (United States)

    Tomas, Ignacio

    simplified version of this model and the corresponding numerical scheme we prove (in addition to stability) convergence and existence of solutions as by-product . Throughout this dissertation, we will provide numerical experiments, not only to validate mathematical results, but also to help the reader gain a qualitative understanding of the PDE models analyzed in this dissertation (the MNSE, the Rosenweig's model, and the Two-phase model). In addition, we also provide computational experiments to illustrate the potential of these simple models and their ability to capture basic phenomenological features of ferrofluids, such as the Rosensweig instability for the case of the two-phase model. In this respect, we highlight the incisive numerical experiments with the two-phase model illustrating the critical role of the demagnetizing field to reproduce physically realistic behavior of ferrofluids.

  20. Torn between dual roles: the experiences of nurse-family members when a loved one is hospitalised in a critical condition.

    Science.gov (United States)

    Giles, Tracey M; Williamson, Victoria

    2015-11-01

    To understand and interpret the experiences of nurse-family members when a family member or loved one is hospitalised in a critical condition. Having a family member hospitalised with a critical illness is a traumatic stressor, often with long-term sequelae. Providing holistic care for family members who are also nurses makes the provision of care more complex because of their professional expertise; yet few studies have explored this issue. In this descriptive study, qualitative data were collected using a questionnaire and analysed using van Manen's (Researching Lived Experience: Human Science for an Action Sensitive Pedagogy, 1990, State University of New York Press, London, ON) six-step approach. Twenty nurse-family members completed an online questionnaire in June 2013. Qualitative findings from 19 participants were included in the analysis. The phenomenological analysis approach described by van Manen (Researching Lived Experience: Human Science for an Action Sensitive Pedagogy, 1990, State University of New York Press, London, ON) was used to describe and interpret nurse-family member experiences. Nurse-family members experience significant dual role conflicts between their personal and professional personas due to their specialised knowledge, need for watchfulness and competing expectations. Our findings describe how dual role conflicts developed and were managed, and reveal the resultant emotional toll and psychological distress as nurse-family members struggled to resolve these conflicts. Nurse-family members require a different type of care than general public family members, yet their unique needs are often unmet, leading to increased anxiety and distress that could potentially be minimised. An increased awareness and emphasis on the nurse-family member experience can ensure health care professionals are better placed to provide appropriate and targeted care to minimise distressing dual role conflicts. There is a need for targeted and specialised

  1. Critical role of types 2 and 3 deiodinases in the negative regulation of gene expression by T₃in the mouse cerebral cortex.

    Science.gov (United States)

    Hernandez, Arturo; Morte, Beatriz; Belinchón, Mónica M; Ceballos, Ainhoa; Bernal, Juan

    2012-06-01

    Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T(3) to nuclear receptors. Brain T(3) concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T(4) and T(3). We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T(3) led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T(3) treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T(3) action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T(3) concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

  2. Two-dimensional critical phenomena

    International Nuclear Information System (INIS)

    Saleur, H.

    1987-09-01

    Two dimensional critical systems are studied using transformation to free fields and conformal invariance methods. The relations between the two approaches are also studied. The analytical results obtained generally depend on universality hypotheses or on renormalization group trajectories which are not established rigorously, so numerical verifications, mainly using the transfer matrix approach, are presented. The exact determination of critical exponents; the partition functions of critical models on toruses; and results as the critical point is approached are discussed [fr

  3. The theoretical strength of rubber: numerical simulations of polyisoprene networks at high tensile strains evidence the role of average chain tortuosity

    International Nuclear Information System (INIS)

    Hanson, David E; Barber, John L

    2013-01-01

    The ultimate stress and strain of polyisoprene rubber were studied by numerical simulations of three-dimensional random networks, subjected to tensile strains high enough to cause chain rupture. Previously published molecular chain force extension models and a numerical network construction procedure were used to perform the simulations for network crosslink densities between 2 × 10 19 and 1 × 10 20 cm −3 , corresponding to experimental dicumyl-peroxide concentrations of 1–5 parts per hundred. At tensile failure (defined as the point of maximum stress), we find that the fraction of network chains ruptured is between 0.1% and 1%, depending on the crosslink density. The fraction of network chains that are taut, i.e. their end-to-end distance is greater than their unstretched contour length, ranges between 10% and 15% at failure. Our model predicts that the theoretical (defect-free) failure stress should be about twice the highest experimental value reported. For extensions approaching failure, tensile stress is dominated by the network morphology and purely enthalpic bond distortion forces and, in this regime, the model has essentially no free parameters. The average initial chain tortuosity (τ) appears to be an important statistical property of rubber networks; if the stress is scaled by τ and the tensile strain is scaled by τ −1 , we obtain a master curve for stress versus strain, valid for all crosslink densities. We derive an analytic expression for the average tortuosity, which is in agreement with values calculated in the simulations. (paper)

  4. Receptor homodimerization plays a critical role in a novel dominant negative P2RY12 variant identified in a family with severe bleeding.

    Science.gov (United States)

    Mundell, S J; Rabbolini, D; Gabrielli, S; Chen, Q; Aungraheeta, R; Hutchinson, J L; Kilo, T; Mackay, J; Ward, C M; Stevenson, W; Morel-Kopp, M-C

    2018-01-01

    Essentials Three dominant variants for the autosomal recessive bleeding disorder type-8 have been described. To date, there has been no phenotype/genotype correlation explaining their dominant transmission. Proline plays an important role in P2Y12R ligand binding and signaling defects. P2Y12R homodimer formation is critical for the receptor function and signaling. Background Although inherited platelet disorders are still underdiagnosed worldwide, advances in molecular techniques are improving disease diagnosis and patient management. Objective To identify and characterize the mechanism underlying the bleeding phenotype in a Caucasian family with an autosomal dominant P2RY12 variant. Methods Full blood counts, platelet aggregometry, flow cytometry and western blotting were performed before next-generation sequencing (NGS). Detailed molecular analysis of the identified variant of the P2Y12 receptor (P2Y12R) was subsequently performed in mammalian cells overexpressing receptor constructs. Results All three referred individuals had markedly impaired ADP-induced platelet aggregation with primary wave only, despite normal total and surface P2Y12R expression. By NGS, a single P2RY12:c.G794C substitution (p.R265P) was identified in all affected individuals, and this was confirmed by Sanger sequencing. Mammalian cell experiments with the R265P-P2Y12R variant showed normal receptor surface expression versus wild-type (WT) P2Y12R. Agonist-stimulated R265P-P2Y12R function (both signaling and surface receptor loss) was reduced versus WT P2Y12R. Critically, R265P-P2Y12R acted in a dominant negative manner, with agonist-stimulated WT P2Y12R activity being reduced by variant coexpression, suggesting dramatic loss of WT homodimers. Importantly, platelet P2RY12 cDNA cloning and sequencing in two affected individuals also revealed three-fold mutant mRNA overexpression, decreasing even further the likelihood of WT homodimer formation. R265 located within extracellular loop 3 (EL3) is

  5. Experimental and Numerical Investigation of Ablation Kinetics

    Data.gov (United States)

    National Aeronautics and Space Administration — The University of Vermont (UVM) and the University of Michigan (UMI) propose a 2-year experimental and numerical research effort aimed at providing critically needed...

  6. Numerical relativity beyond astrophysics

    Science.gov (United States)

    Garfinkle, David

    2017-01-01

    Though the main applications of computer simulations in relativity are to astrophysical systems such as black holes and neutron stars, nonetheless there are important applications of numerical methods to the investigation of general relativity as a fundamental theory of the nature of space and time. This paper gives an overview of some of these applications. In particular we cover (i) investigations of the properties of spacetime singularities such as those that occur in the interior of black holes and in big bang cosmology. (ii) investigations of critical behavior at the threshold of black hole formation in gravitational collapse. (iii) investigations inspired by string theory, in particular analogs of black holes in more than 4 spacetime dimensions and gravitational collapse in spacetimes with a negative cosmological constant.

  7. Numerical relativity beyond astrophysics.

    Science.gov (United States)

    Garfinkle, David

    2017-01-01

    Though the main applications of computer simulations in relativity are to astrophysical systems such as black holes and neutron stars, nonetheless there are important applications of numerical methods to the investigation of general relativity as a fundamental theory of the nature of space and time. This paper gives an overview of some of these applications. In particular we cover (i) investigations of the properties of spacetime singularities such as those that occur in the interior of black holes and in big bang cosmology. (ii) investigations of critical behavior at the threshold of black hole formation in gravitational collapse. (iii) investigations inspired by string theory, in particular analogs of black holes in more than 4 spacetime dimensions and gravitational collapse in spacetimes with a negative cosmological constant.

  8. Thinking Critically about Critical Thinking

    Science.gov (United States)

    Mulnix, Jennifer Wilson

    2012-01-01

    As a philosophy professor, one of my central goals is to teach students to think critically. However, one difficulty with determining whether critical thinking can be taught, or even measured, is that there is widespread disagreement over what critical thinking actually is. Here, I reflect on several conceptions of critical thinking, subjecting…

  9. A critical role of nucleus accumbens dopamine D1-family receptors in renewal of alcohol seeking after punishment-imposed abstinence.

    Science.gov (United States)

    Marchant, Nathan J; Kaganovsky, Konstantin

    2015-06-01

    In humans, places or contexts previously associated with alcohol use often provoke relapse during abstinence. This phenomenon is modeled in laboratory animals using the ABA renewal procedure, in which extinction training in context (B) suppresses alcohol seeking, and renewal of this seeking occurs when the animal returns to the original training context (A). However, extinction training does not adequately capture the motivation for abstinence in human alcoholics who typically self-initiate abstinence in response to the negative consequences of excessive use. We recently developed a procedure to study renewal in laboratory rats after abstinence imposed by negative consequences (footshock punishment). The mechanisms of renewal of punished alcohol seeking are largely unknown. Here, we used the D1-family receptor antagonist SCH 23390 to examine the role of nucleus accumbens (NAc) shell and core dopamine in renewal of alcohol seeking after punishment-imposed abstinence. We trained alcohol-preferring "P rats" to self-administer 20% alcohol in Context A and subsequently suppressed alcohol taking via response-contingent footshock punishment in Context B. We tested the effects of systemic, NAc shell, or NAc core injections of SCH 23390 on renewal of alcohol seeking after punishment-imposed abstinence. We found that both systemic and NAc shell and core injections of SCH 23390 decreased renewal of punished alcohol seeking. Our results demonstrate a critical role of NAc dopamine in renewal of alcohol seeking after punishment-imposed abstinence. We discuss these results in reference to the brain mechanisms of renewal of alcohol seeking after extinction versus punishment. (c) 2015 APA, all rights reserved).

  10. Critical role of free cytosolic calcium, but not uncoupling, in mitochondrial permeability transition and cell death induced by diclofenac oxidative metabolites in immortalized human hepatocytes

    International Nuclear Information System (INIS)

    Lim, M.S.; Lim, Priscilla L.K.; Gupta, Rashi; Boelsterli, Urs A.

    2006-01-01

    Diclofenac is a widely used nonsteroidal anti-inflammatory drug that has been associated with rare but serious hepatotoxicity. Experimental evidence indicates that diclofenac targets mitochondria and induces the permeability transition (mPT) which leads to apoptotic cell death in hepatocytes. While the downstream effector mechanisms have been well characterized, the more proximal pathways leading to the mPT are not known. The purpose of this study was to explore the role of free cytosolic calcium (Ca 2+ c ) in diclofenac-induced cell injury in immortalized human hepatocytes. We show that exposure to diclofenac caused time- and concentration-dependent cell injury, which was prevented by the specific mPT inhibitor cyclosporin A (CsA, 5 μM). At 8 h, diclofenac caused increases in [Ca 2+ ] c (Fluo-4 fluorescence), which was unaffected by CsA. Combined exposure to diclofenac/BAPTA (Ca 2+ chelator) inhibited cell injury, indicating that Ca 2+ plays a critical role in precipitating mPT. Diclofenac decreased the mitochondrial membrane potential, ΔΨ m (JC-1 fluorescence), even in the presence of CsA or BAPTA, indicating that mitochondrial depolarization was not a consequence of the mPT or elevated [Ca 2+ ] c . The CYP2C9 inhibitor sulphaphenazole (10 μM) protected from diclofenac-induced cell injury and prevented increases in [Ca 2+ ] c , while it had no effect on the dissipation of the ΔΨ m . Finally, diclofenac exposure greatly increased the mitochondria-selective superoxide levels secondary to the increases in [Ca 2+ ] c . In conclusion, these data demonstrate that diclofenac has direct depolarizing effects on mitochondria which does not lead to cell injury, while CYP2C9-mediated bioactivation causes increases in [Ca 2+ ] c , triggering the mPT and precipitating cell death

  11. Huntingtin-Interacting Protein 1-Related Protein Plays a Critical Role in Dendritic Development and Excitatory Synapse Formation in Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Lin Peng

    2017-06-01

    Full Text Available Huntingtin-interacting protein 1-related (HIP1R protein is considered to be an endocytic adaptor protein like the other two members of the Sla2 family, Sla2p and HIP1. They all contain homology domains responsible for the binding of clathrin, inositol lipids and F-actin. Previous studies have revealed that HIP1R is highly expressed in different regions of the mouse brain and localizes at synaptic structures. However, the function of HIP1R in the nervous system remains unknown. In this study, we investigated HIP1R function in cultured rat hippocampal neurons using an shRNA knockdown approach. We found that, after HIP1R knockdown, the dynamics and density of dendritic filopodia, and dendritic branching and complexity were significantly reduced in developing neurons, as well as the densities of dendritic spines and PSD95 clusters in mature neurons. Moreover, HIP1R deficiency led to significantly reduced expression of the ionotropic glutamate receptor GluA1, GluN2A and GluN2B subunits, but not the GABAA receptor α1 subunit. Similarly, HIP1R knockdown reduced the amplitude and frequency of the miniature excitatory postsynaptic current, but not of the miniature inhibitory postsynaptic current. In addition, the C-terminal proline-rich region of HIP1R responsible for cortactin binding was found to confer a dominant-negative effect on dendritic branching in cultured developing neurons, implying a critical role of cortactin binding in HIP1R function. Taken together, the results of our study suggest that HIP1R plays important roles in dendritic development and excitatory synapse formation and function.

  12. A critical review of the postulated role of the non-essential amino acid, β-N-methylamino-L-alanine, in neurodegenerative disease in humans

    Science.gov (United States)

    Chernoff, Neil; Hill, D. J.; Diggs, D. L.; Faison, B. D.; Francis, B. M.; Lang, J. R.; Larue, M. M.; Le, T.-T.; Loftin, Keith A.; Lugo, J. N.; Schmid, J. E.; Winnik, W. W.

    2017-01-01

    The compound BMAA (β-N-methylamino-L-alanine) has been postulated to play a significant role in four serious neurological human diseases: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, Parkinsonism, and dementia that occur globally. ALS/PDC with symptoms of all three diseases first came to the attention of the scientific community during and after World War II. It was initially associated with cycad flour used for food because BMAA is a product of symbiotic cycad root-dwelling cyanobacteria. Human consumption of flying foxes that fed on cycad seeds was later suggested as a source of BMAA on Guam and a cause of ALS/PDC. Subsequently, the hypothesis was expanded to include a causative role for BMAA in other neurodegenerative diseases including Alzheimer’s disease (AD) through exposures attributed to proximity to freshwaters and/or consumption of seafood due to its purported production by most species of cyanobacteria. The hypothesis that BMAA is the critical factor in the genesis of these neurodegenerative diseases received considerable attention in the medical, scientific, and public arenas. This review examines the history of ALS/PDC and the BMAA-human disease hypotheses; similarities and differences between ALS/PDC and the other diseases with similar symptomologies; the relationship of ALS/PDC to other similar diseases, studies of BMAA-mediated effects in lab animals, inconsistencies and data gaps in the hypothesis; and other compounds and agents that were suggested as the cause of ALS/PDC on Guam. The review concludes that the hypothesis of a causal BMAA neurodegenerative disease relationship is not supported by existing data.

  13. The lipopolysaccharide core oligosaccharide of Burkholderia plays a critical role in maintaining a proper gut symbiosis with the bean bug Riptortus pedestris.

    Science.gov (United States)

    Kim, Jiyeun Kate; Jang, Ho Am; Kim, Min Seon; Cho, Jae Hyun; Lee, Junbeom; Di Lorenzo, Flaviana; Sturiale, Luisa; Silipo, Alba; Molinaro, Antonio; Lee, Bok Luel

    2017-11-24

    Lipopolysaccharide, the outer cell-wall component of Gram-negative bacteria, has been shown to be important for symbiotic associations. We recently reported that the lipopolysaccharide O-antigen of Burkholderia enhances the initial colonization of the midgut of the bean bug, Riptortus pedestris However, the midgut-colonizing Burkholderia symbionts lack the O-antigen but display the core oligosaccharide on the cell surface. In this study, we investigated the role of the core oligosaccharide, which directly interacts with the host midgut, in the Riptortus-Burkholderia symbiosis. To this end, we generated the core oligosaccharide mutant strains, Δ wabS , Δ wabO , Δ waaF, and Δ waaC, and determined the chemical structures of their oligosaccharides, which exhibited different compositions. The symbiotic properties of these mutant strains were compared with those of the wild-type and O-antigen-deficient Δ wbiG strains. Upon introduction into Riptortus via the oral route, the core oligosaccharide mutant strains exhibited different rates of colonization of the insect midgut. The symbiont titers in fifth-instar insects revealed significantly reduced population sizes of the inner core oligosaccharide mutant strains Δ waaF and Δ waaC These two strains also negatively affected host growth rate and fitness. Furthermore, R. pedestris individuals colonized with the Δ waaF and Δ waaC strains were vulnerable to septic bacterial challenge, similar to insects without a Burkholderia symbiont. Taken together, these results suggest that the core oligosaccharide from Burkholderia symbionts plays a critical role in maintaining a proper symbiont population and in supporting the beneficial effects of the symbiont on its host in the Riptortus-Burkholderia symbiosis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Toward critical bioethics.

    Science.gov (United States)

    Árnason, Vilhjálmur

    2015-04-01

    This article deals with the question as to what makes bioethics a critical discipline. It considers different senses of criticism and evaluates their strengths and weaknesses. A primary method in bioethics as a philosophical discipline is critical thinking, which implies critical evaluation of concepts, positions, and arguments. It is argued that the type of analytical criticism that restricts its critical role to critical thinking of this type often suffers from other intellectual flaws. Three examples are taken to demonstrate this: premature criticism, uncritical self-understanding of theoretical assumptions, and narrow framing of bioethical issues. Such flaws can lead both to unfair treatment of authors and to uncritical discussion of topics. In this context, the article makes use of Häyry's analysis of different rationalities in bioethical approaches and argues for the need to recognize the importance of communicative rationality for critical bioethics. A radically different critical approach i