WorldWideScience

Sample records for model involving cns-2

  1. Modeling interdisciplinary activities involving Mathematics

    DEFF Research Database (Denmark)

    Iversen, Steffen Møllegaard

    2006-01-01

    In this paper a didactical model is presented. The goal of the model is to work as a didactical tool, or conceptual frame, for developing, carrying through and evaluating interdisciplinary activities involving the subject of mathematics and philosophy in the high schools. Through the terms...... domains (Michelsen, 2001, 2005a, 2005b). Furthermore the theoretical description rest on a series of qualitative interviews with teachers from the Danish high school (grades 9-11) conducted recently. The special case of concrete interdisciplinary activities between mathematics and philosophy is also...

  2. Modeling interdisciplinary activities involving Mathematics

    DEFF Research Database (Denmark)

    Iversen, Steffen Møllegaard

    2006-01-01

    In this paper a didactical model is presented. The goal of the model is to work as a didactical tool, or conceptual frame, for developing, carrying through and evaluating interdisciplinary activities involving the subject of mathematics and philosophy in the high schools. Through the terms...... of Horizontal Intertwining, Vertical Structuring and Horizontal Propagation the model consists of three phases, each considering different aspects of the nature of interdisciplinary activities. The theoretical modelling is inspired by work which focuses on the students abilities to concept formation in expanded...... domains (Michelsen, 2001, 2005a, 2005b). Furthermore the theoretical description rest on a series of qualitative interviews with teachers from the Danish high school (grades 9-11) conducted recently. The special case of concrete interdisciplinary activities between mathematics and philosophy is also...

  3. Observations involving broadband impedance modelling

    Energy Technology Data Exchange (ETDEWEB)

    Berg, J.S. [Stanford Linear Accelerator Center, Menlo Park, CA (United States)

    1996-08-01

    Results for single- and multi-bunch instabilities can be significantly affected by the precise model that is used for the broadband impedance. This paper discusses three aspects of broadband impedance modelling. The first is an observation of the effect that a seemingly minor change in an impedance model has on the single-bunch mode coupling threshold. The second is a successful attempt to construct a model for the high-frequency tails of an r.f. cavity. The last is a discussion of requirements for the mathematical form of an impedance which follow from the general properties of impedances. (author)

  4. Observations involving broadband impedance modelling

    Energy Technology Data Exchange (ETDEWEB)

    Berg, J.S.

    1995-08-01

    Results for single- and multi-bunch instabilities can be significantly affected by the precise model that is used for the broadband impendance. This paper discusses three aspects of broadband impendance modeling. The first is an observation of the effect that a seemingly minor change in an impedance model has on the single-bunch mode coupling threshold. The second is a successful attempt to construct a model for the high-frequency tails of an r.f cavity. The last is a discussion of requirements for the mathematical form of an impendance which follow from the general properties of impendances.

  5. Bullying Prevention and the Parent Involvement Model

    Science.gov (United States)

    Kolbert, Jered B.; Schultz, Danielle; Crothers, Laura M.

    2014-01-01

    A recent meta-analysis of bullying prevention programs provides support for social-ecological theory, in which parent involvement addressing child bullying behaviors is seen as important in preventing school-based bullying. The purpose of this manuscript is to suggest how Epstein and colleagues' parent involvement model can be used as a…

  6. Learning models of activities involving interacting objects

    DEFF Research Database (Denmark)

    Manfredotti, Cristina; Pedersen, Kim Steenstrup; Hamilton, Howard J.;

    2013-01-01

    We propose the LEMAIO multi-layer framework, which makes use of hierarchical abstraction to learn models for activities involving multiple interacting objects from time sequences of data concerning the individual objects. Experiments in the sea navigation domain yielded learned models that were...

  7. Learning models of activities involving interacting objects

    DEFF Research Database (Denmark)

    Manfredotti, Cristina; Pedersen, Kim Steenstrup; Hamilton, Howard J.

    2013-01-01

    We propose the LEMAIO multi-layer framework, which makes use of hierarchical abstraction to learn models for activities involving multiple interacting objects from time sequences of data concerning the individual objects. Experiments in the sea navigation domain yielded learned models that were t...

  8. Learning models of activities involving interacting objects

    DEFF Research Database (Denmark)

    Manfredotti, Cristina; Pedersen, Kim Steenstrup; Hamilton, Howard J.;

    2013-01-01

    We propose the LEMAIO multi-layer framework, which makes use of hierarchical abstraction to learn models for activities involving multiple interacting objects from time sequences of data concerning the individual objects. Experiments in the sea navigation domain yielded learned models that were...... then successfully applied to activity recognition, activity simulation and multi-target tracking. Our method compares favourably with respect to previously reported results using Hidden Markov Models and Relational Particle Filtering....

  9. Modeling fault among motorcyclists involved in crashes.

    Science.gov (United States)

    Haque, Md Mazharul; Chin, Hoong Chor; Huang, Helai

    2009-03-01

    Singapore crash statistics from 2001 to 2006 show that the motorcyclist fatality and injury rates per registered vehicle are higher than those of other motor vehicles by 13 and 7 times, respectively. The crash involvement rate of motorcyclists as victims of other road users is also about 43%. The objective of this study is to identify the factors that contribute to the fault of motorcyclists involved in crashes. This is done by using the binary logit model to differentiate between at-fault and not-at-fault cases and the analysis is further categorized by the location of the crashes, i.e., at intersections, on expressways and at non-intersections. A number of explanatory variables representing roadway characteristics, environmental factors, motorcycle descriptions, and rider demographics have been evaluated. Time trend effect shows that not-at-fault crash involvement of motorcyclists has increased with time. The likelihood of night time crashes has also increased for not-at-fault crashes at intersections and expressways. The presence of surveillance cameras is effective in reducing not-at-fault crashes at intersections. Wet-road surfaces increase at-fault crash involvement at non-intersections. At intersections, not-at-fault crash involvement is more likely on single-lane roads or on median lane of multi-lane roads, while on expressways at-fault crash involvement is more likely on the median lane. Roads with higher speed limit have higher at-fault crash involvement and this is also true on expressways. Motorcycles with pillion passengers or with higher engine capacity have higher likelihood of being at-fault in crashes on expressways. Motorcyclists are more likely to be at-fault in collisions involving pedestrians and this effect is higher at night. In multi-vehicle crashes, motorcyclists are more likely to be victims than at-fault. Young and older riders are more likely to be at-fault in crashes than middle-aged group of riders. The findings of this study will help

  10. Modeling human operator involvement in robotic systems

    NARCIS (Netherlands)

    Wewerinke, P.H.

    1991-01-01

    A modeling approach is presented to describe complex manned robotic systems. The robotic system is modeled as a (highly) nonlinear, possibly time-varying dynamic system including any time delays in terms of optimal estimation, control and decision theory. The role of the human operator(s) is modeled

  11. Buried Waste Integrated Demonstration stakeholder involvement model

    Energy Technology Data Exchange (ETDEWEB)

    Kaupanger, R.M.; Kostelnik, K.M.; Milam, L.M.

    1994-04-01

    The Buried Waste Integrated Demonstration (BWID) is a program funded by the US Department of Energy (DOE) Office of Technology Development. BWID supports the applied research, development, demonstration, and evaluation of a suite of advanced technologies that together form a comprehensive remediation system for the effective and efficient remediation of buried waste. Stakeholder participation in the DOE Environmental Management decision-making process is critical to remediation efforts. Appropriate mechanisms for communication with the public, private sector, regulators, elected officials, and others are being aggressively pursued by BWID to permit informed participation. This document summarizes public outreach efforts during FY-93 and presents a strategy for expanded stakeholder involvement during FY-94.

  12. Combinatorial Model Involving Stochastic Choices of Destination, Mode and Route

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Traffic assignment models are one of the basic tools for the analysis and design of transportation systems. However, the existing models have some defects. Considering the characteristics of Chinese urban mixed traffic and the randomness of transportation information, the author develops a combinatorial model involving stochastic choices of destination, mode and route. Its uniqueness and equivalance are also proved by the optimization theory.

  13. Five challenges for stochastic epidemic models involving global transmission

    Directory of Open Access Journals (Sweden)

    Tom Britton

    2015-03-01

    Full Text Available The most basic stochastic epidemic models are those involving global transmission, meaning that infection rates depend only on the type and state of the individuals involved, and not on their location in the population. Simple as they are, there are still several open problems for such models. For example, when will such an epidemic go extinct and with what probability (questions depending on the population being fixed, changing or growing? How can a model be defined explaining the sometimes observed scenario of frequent mid-sized epidemic outbreaks? How can evolution of the infectious agent transmission rates be modelled and fitted to data in a robust way?

  14. A consumer involvement model for health technology assessment in Canada.

    Science.gov (United States)

    Pivik, Jayne; Rode, Elisabeth; Ward, Christopher

    2004-08-01

    Similar to other health policy initiatives, there is a growing movement to involve consumers in decisions affecting their treatment options. Access to treatments can be impacted by decisions made during a health technology assessment (HTA), i.e., the rigorous assessment of medical interventions such as drugs, vaccines, devices, materials, medical and surgical procedures and systems. The purpose of this paper was to empirically assess the interest and potential mechanisms for consumer involvement in HTA by identifying what health consumer organizations consider meaningful involvement, examining current practices internationally and developing a model for involvement based on identified priorities and needs. Canadian health consumer groups representing the largest disease or illness conditions reported a desire for involvement in HTA and provided feedback on mechanisms for facilitating their involvement.

  15. Transactional Models Between Personality and Alcohol Involvement: A Further Examination

    OpenAIRE

    2012-01-01

    Although correlated changes between personality and alcohol involvement have been shown, the functional relation between these constructs is also of theoretical and clinical interest. Using bivariate latent difference score models, we examined transactional relations (i.e., personality predicting changes in alcohol involvement, which in turn predicts changes in personality) across two distinct but overlapping developmental time frames (i.e., across college and during young adulthood) using tw...

  16. Positive Solutions for a Competition Model with an Inhibitor Involved

    Institute of Scientific and Technical Information of China (English)

    Bin Chen

    2008-01-01

    In the paper, we study the positive solutions of a diffusive competition model with an inhibitor involved subject to the homogeneous Dirichlet boundary condition. The existence, uniqueness, stability and multiplicity of positive solutions are discussed. This is mainly done by using the local and global bifurcation theory.

  17. A Process Model of Organizational Commitment and Job Involvement.

    Science.gov (United States)

    1982-09-01

    AD-A123 043 A PROCESS MODEL OF ORGANIZATIONAL COMMITMENT AND JOB I INVOLVEMENT(U) AIR FORCE INST OF TECH WR IGHT PATTERSON AFB OH SCHOL OF SYSTEMS...Appo @1 inu pubo 01004 Aocesston For NTIS CRA&I DTIC TAB Unannounced 0I Justfication - gI, Distr" ’ut ioi / Af t A PROCESS MODEL OF ORGANIZATIONAL...GOVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER LSSR 76-82 1,3b - 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED A PROCESS MODEL OF

  18. Environmental Management Model for Road Maintenance Operation Involving Community Participation

    Science.gov (United States)

    Triyono, A. R. H.; Setyawan, A.; Sobriyah; Setiono, P.

    2017-07-01

    Public expectations of Central Java, which is very high on demand fulfillment, especially road infrastructure as outlined in the number of complaints and community expectations tweeter, Short Mail Massage (SMS), e-mail and public reports from various media, Highways Department of Central Java province requires development model of environmental management in the implementation of a routine way by involving the community in order to fulfill the conditions of a representative, may serve road users safely and comfortably. This study used survey method with SEM analysis and SWOT with Latent Independent Variable (X), namely; Public Participation in the regulation, development, construction and supervision of road (PSM); Public behavior in the utilization of the road (PMJ) Provincial Road Service (PJP); Safety in the Provincial Road (KJP); Integrated Management System (SMT) and latent dependent variable (Y) routine maintenance of the provincial road that is integrated with the environmental management system and involve the participation of the community (MML). The result showed the implementation of routine maintenance of road conditions in Central Java province has yet to implement an environmental management by involving the community; Therefore developed environmental management model with the results of H1: Community Participation (PSM) has positive influence on the Model of Environmental Management (MML); H2: Behavior Society in Jalan Utilization (PMJ) positive effect on Model Environmental Management (MML); H3: Provincial Road Service (PJP) positive effect on Model Environmental Management (MML); H4: Safety in the Provincial Road (KJP) positive effect on Model Environmental Management (MML); H5: Integrated Management System (SMT) has positive influence on the Model of Environmental Management (MML). From the analysis obtained formulation model describing the relationship / influence of the independent variables PSM, PMJ, PJP, KJP, and SMT on the dependent variable

  19. Involving stakeholders in building integrated fisheries models using Bayesian methods.

    Science.gov (United States)

    Haapasaari, Päivi; Mäntyniemi, Samu; Kuikka, Sakari

    2013-06-01

    A participatory Bayesian approach was used to investigate how the views of stakeholders could be utilized to develop models to help understand the Central Baltic herring fishery. In task one, we applied the Bayesian belief network methodology to elicit the causal assumptions of six stakeholders on factors that influence natural mortality, growth, and egg survival of the herring stock in probabilistic terms. We also integrated the expressed views into a meta-model using the Bayesian model averaging (BMA) method. In task two, we used influence diagrams to study qualitatively how the stakeholders frame the management problem of the herring fishery and elucidate what kind of causalities the different views involve. The paper combines these two tasks to assess the suitability of the methodological choices to participatory modeling in terms of both a modeling tool and participation mode. The paper also assesses the potential of the study to contribute to the development of participatory modeling practices. It is concluded that the subjective perspective to knowledge, that is fundamental in Bayesian theory, suits participatory modeling better than a positivist paradigm that seeks the objective truth. The methodology provides a flexible tool that can be adapted to different kinds of needs and challenges of participatory modeling. The ability of the approach to deal with small data sets makes it cost-effective in participatory contexts. However, the BMA methodology used in modeling the biological uncertainties is so complex that it needs further development before it can be introduced to wider use in participatory contexts.

  20. Involving Stakeholders in Building Integrated Fisheries Models Using Bayesian Methods

    Science.gov (United States)

    Haapasaari, Päivi; Mäntyniemi, Samu; Kuikka, Sakari

    2013-06-01

    A participatory Bayesian approach was used to investigate how the views of stakeholders could be utilized to develop models to help understand the Central Baltic herring fishery. In task one, we applied the Bayesian belief network methodology to elicit the causal assumptions of six stakeholders on factors that influence natural mortality, growth, and egg survival of the herring stock in probabilistic terms. We also integrated the expressed views into a meta-model using the Bayesian model averaging (BMA) method. In task two, we used influence diagrams to study qualitatively how the stakeholders frame the management problem of the herring fishery and elucidate what kind of causalities the different views involve. The paper combines these two tasks to assess the suitability of the methodological choices to participatory modeling in terms of both a modeling tool and participation mode. The paper also assesses the potential of the study to contribute to the development of participatory modeling practices. It is concluded that the subjective perspective to knowledge, that is fundamental in Bayesian theory, suits participatory modeling better than a positivist paradigm that seeks the objective truth. The methodology provides a flexible tool that can be adapted to different kinds of needs and challenges of participatory modeling. The ability of the approach to deal with small data sets makes it cost-effective in participatory contexts. However, the BMA methodology used in modeling the biological uncertainties is so complex that it needs further development before it can be introduced to wider use in participatory contexts.

  1. Modeling supercritical fluid extraction process involving solute-solid interaction

    Energy Technology Data Exchange (ETDEWEB)

    Goto, M.; Roy, B. Kodama, A.; Hirose, T. [Kumamoto Univ., Kumamoto (Japan)

    1998-04-01

    Extraction or leaching of solute from natural solid material is a mass transfer process involving dissolution or release of solutes from a solid matrix. Interaction between the solute and solid matrix often influences the supercritical fluid extraction process. A model accounting for the solute-solid interaction as well as mass transfer is developed. The BET equation is used to incorporate the interaction and the solubility of solutes into the local equilibrium in the model. Experimental data for the supercritical extraction of essential oil and cuticular wax from peppermint leaves are successfully analyzed by the model. The effects of parameters on the extraction behavior are demonstrated to illustrate the concept of the model. 18 refs., 5 figs., 1 tab.

  2. Proposed best practice for projects that involve modelling and simulation.

    Science.gov (United States)

    O'Kelly, Michael; Anisimov, Vladimir; Campbell, Chris; Hamilton, Sinéad

    2017-03-01

    Modelling and simulation has been used in many ways when developing new treatments. To be useful and credible, it is generally agreed that modelling and simulation should be undertaken according to some kind of best practice. A number of authors have suggested elements required for best practice in modelling and simulation. Elements that have been suggested include the pre-specification of goals, assumptions, methods, and outputs. However, a project that involves modelling and simulation could be simple or complex and could be of relatively low or high importance to the project. It has been argued that the level of detail and the strictness of pre-specification should be allowed to vary, depending on the complexity and importance of the project. This best practice document does not prescribe how to develop a statistical model. Rather, it describes the elements required for the specification of a project and requires that the practitioner justify in the specification the omission of any of the elements and, in addition, justify the level of detail provided about each element. This document is an initiative of the Special Interest Group for modelling and simulation. The Special Interest Group for modelling and simulation is a body open to members of Statisticians in the Pharmaceutical Industry and the European Federation of Statisticians in the Pharmaceutical Industry. Examples of a very detailed specification and a less detailed specification are included as appendices. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Mathematical modeling of variables involved in dissolution testing.

    Science.gov (United States)

    Gao, Zongming

    2011-11-01

    Dissolution testing is an important technique used for development and quality control of solid oral dosage forms of pharmaceutical products. However, the variability associated with this technique, especially with USP apparatuses 1 and 2, is a concern for both the US Food and Drug Administration and pharmaceutical companies. Dissolution testing involves a number of variables, which can be divided into four main categories: (1) analyst, (2) dissolution apparatus, (3) testing environment, and (4) sample. Both linear and nonlinear models have been used to study dissolution profiles, and various mathematical functions have been used to model the observed data. In this study, several variables, including dissolved gases in the dissolution medium, off-center placement of the test tablet, environmental vibration, and various agitation speeds, were modeled. Mathematical models including Higuchi, Korsmeyer-Peppas, Weibull, and the Noyes-Whitney equation were employed to study the dissolution profile of 10 mg prednisone tablets (NCDA #2) using the USP paddle method. The results showed that the nonlinear models (Korsmeyer-Peppas and Weibull) accurately described the entire dissolution profile. The results also showed that dissolution variables affected dissolution rate constants differently, depending on whether the tablets disintegrated or dissolved.

  4. Effectiveness of Peer Education Involving the use of Theoretical Models

    OpenAIRE

    2008-01-01

    The effectiveness of health education among university students who received peer-support training was investigated using four theoretical models : the health belief model, the self-efficacy model, social support and the transtheoretical model of health behavior change. Results suggested that the four theoretical models were useful in evaluating the effect of peer education as an alternative assessment tool. In light of this, it is suggested that the use of the theoretical models may facilita...

  5. Lithium-ion batteries modeling involving fractional differentiation

    Science.gov (United States)

    Sabatier, Jocelyn; Merveillaut, Mathieu; Francisco, Junior Mbala; Guillemard, Franck; Porcelatto, Denis

    2014-09-01

    With hybrid and electric vehicles development, automobile battery monitoring systems (BMS) have to meet the new requirements. These systems have to give information on state of health, state of charge, available power. To get this information, BMS often implement battery models. Accuracy of the information manipulated by the BMS thus depends on the model accuracy. This paper is within this framework and addresses lithium-ion battery modeling. The proposed fractional model is based on simplifications of an electrochemical model and on resolution of some partial differential equations used in its description. Such an approach permits to get a simple model in which electrochemical variables and parameters still appear.

  6. Dispersion modelling approaches for near road applications involving noise barriers

    Science.gov (United States)

    The talk will present comparisons with two datasets of the barrier algorithms implemented in two different dispersion models: US EPA’s R-LINE (a research dispersion modelling tool under development by the US EPA’s Office of Research and Development) and CERC’s A...

  7. Mouse models for genes involved in impaired spermatogenesis.

    Science.gov (United States)

    O'Bryan, M K; de Kretser, D

    2006-02-01

    Since the introduction of molecular biology and gene ablation technologies there have been substantial advances in our understanding of how sperm are made and fertilization occurs. There have been at least 150 different models of specifically altered gene function produced that have resulted in male infertility spanning virtually all aspects of the spermatogenic, sperm maturation and fertilization processes. While each has, or potentially will reveal, novel aspects of these processes, there is still much of which we have little knowledge. The current review is by no means a comprehensive list of these mouse models, rather it gives an overview of the potential for such models which up to this point have generally been 'knockouts'; it presents alternative strategies for the production of new models and emphasizes the importance of thorough phenotypic analysis in order to extract a maximum amount of information from each model.

  8. Pedigree models for complex human traits involving the mitochrondrial genome

    Energy Technology Data Exchange (ETDEWEB)

    Schork, N.J.; Guo, S.W. (Univ. of Michigan, Ann Arbor, MI (United States))

    1993-12-01

    Recent biochemical and molecular-genetic discoveries concerning variations in human mtDNA have suggested a role for mtDNA mutations in a number of human traits and disorders. Although the importance of these discoveries cannot be emphasized enough, the complex natures of mitochondrial biogenesis, mutant mtDNA phenotype expression, and the maternal inheritance pattern exhibited by mtDNA transmission make it difficult to develop models that can be used routinely in pedigree analyses to quantify and test hypotheses about the role of mtDNA in the expression of a trait. In the present paper, the authors describe complexities inherent in mitochondrial biogenesis and genetic transmission and show how these complexities can be incorporated into appropriate mathematical models. The authors offer a variety of likelihood-based models which account for the complexities discussed. The derivation of the models is meant to stimulate the construction of statistical tests for putative mtDNA contribution to a trait. Results of simulation studies which make use of the proposed models are described. The results of the simulation studies suggest that, although pedigree models of mtDNA effects can be reliable, success in mapping chromosomal determinants of a trait does not preclude the possibility that mtDNA determinants exist for the trait as well. Shortcomings inherent in the proposed models are described in an effort to expose areas in need of additional research. 58 refs., 5 figs., 2 tabs.

  9. A COUPLED MORPHODYNAMIC MODEL FOR APPLICATIONS INVOLVING WETTING AND DRYING*

    Institute of Scientific and Technical Information of China (English)

    LIANG Qiuhua

    2011-01-01

    This work presents a new finite volume Godunov-type model for predicting morphological changes under the rapidly varying flood conditions with wetting and drying. The model solves the coupled shallow water and Exner equations, with the interface fluxes evaluated by an Harten-Lax-van Leer-Contact (HLLC) approximate Riemann solver. Well-balanced solution is achieved using the surface gradient method and wetting and drying are handled by a non-negative reconstruction approach. The new model is validated against several theoretical benchmark tests and promising results are obtained.

  10. Modeling and Compensatory Processes Underlying Involvement in Child Care among Kibbutz-Reared Fathers

    Science.gov (United States)

    Gaunt, Ruth; Bassi, Liat

    2012-01-01

    This study examined modeling and compensatory processes underlying the effects of an early paternal model on father involvement in child care. Drawing on social learning theory, it was hypothesized that father-son relationships would moderate the association between a father's involvement and his own father's involvement. A sample of 136 kibbutz…

  11. Modeling of nonlinear responses for reciprocal transducers involving polarization switching

    DEFF Research Database (Denmark)

    Willatzen, Morten; Wang, Linxiang

    2007-01-01

    Nonlinearities and hysteresis effects in a reciprocal PZT transducer are examined by use of a dynamical mathematical model on the basis of phase-transition theory. In particular, we consider the perovskite piezoelectric ceramic in which the polarization process in the material can be modeled....... We present numerical results for the reciprocal-transducer system and identify the influence of nonlinearities on the system dynamics at high and low frequency as well as electrical impedance effects due to tuning by a series inductance. It is found that nonlinear effects are not important at high...... by Landau theory for the first-order phase transformation, in which each polarization state is associated with a minimum of the Landau free-energy function. Nonlinear constitutive laws are obtained by using thermodynamical equilibrium conditions, and hysteretic behavior of the material can be modeled...

  12. The Coriolis Effect: A Model for Student Involvement

    Science.gov (United States)

    Exline, Joseph D.

    1977-01-01

    Lists materials and procedures for constructing a model that demonstrates certain aspects of the Coriolis effect. Materials include an electric drill motor, voltage control, toy dart gun and darts, wood blocks of varying dimensions. Includes description of an experiment illustrating relationship between speed of rotation and amount of apparent…

  13. Mechanism involved in the UCB neurotoxicity on cellular models

    OpenAIRE

    Giraudi, Pablo Jose'

    2009-01-01

    Summary This doctoral thesis covers three years period (2006-2008) during which I have investigated the bilirubin neurotoxicity in the neuroblastoma SH-SY5Y cell line, a neuronal cell model widely used in the study of the pathogenesis and in the development of new therapeutic compounds for neurodegenerative diseases. In the first chapter is summarized the current knowledge about bilirubin chemistry and metabolism including disorders of bilirubin metabolism and the neuronal disturbanc...

  14. Sleeping Beauty mouse models identify candidate genes involved in gliomagenesis.

    Science.gov (United States)

    Vyazunova, Irina; Maklakova, Vilena I; Berman, Samuel; De, Ishani; Steffen, Megan D; Hong, Won; Lincoln, Hayley; Morrissy, A Sorana; Taylor, Michael D; Akagi, Keiko; Brennan, Cameron W; Rodriguez, Fausto J; Collier, Lara S

    2014-01-01

    Genomic studies of human high-grade gliomas have discovered known and candidate tumor drivers. Studies in both cell culture and mouse models have complemented these approaches and have identified additional genes and processes important for gliomagenesis. Previously, we found that mobilization of Sleeping Beauty transposons in mice ubiquitously throughout the body from the Rosa26 locus led to gliomagenesis with low penetrance. Here we report the characterization of mice in which transposons are mobilized in the Glial Fibrillary Acidic Protein (GFAP) compartment. Glioma formation in these mice did not occur on an otherwise wild-type genetic background, but rare gliomas were observed when mobilization occurred in a p19Arf heterozygous background. Through cloning insertions from additional gliomas generated by transposon mobilization in the Rosa26 compartment, several candidate glioma genes were identified. Comparisons to genetic, epigenetic and mRNA expression data from human gliomas implicates several of these genes as tumor suppressor genes and oncogenes in human glioblastoma.

  15. Sleeping Beauty mouse models identify candidate genes involved in gliomagenesis.

    Directory of Open Access Journals (Sweden)

    Irina Vyazunova

    Full Text Available Genomic studies of human high-grade gliomas have discovered known and candidate tumor drivers. Studies in both cell culture and mouse models have complemented these approaches and have identified additional genes and processes important for gliomagenesis. Previously, we found that mobilization of Sleeping Beauty transposons in mice ubiquitously throughout the body from the Rosa26 locus led to gliomagenesis with low penetrance. Here we report the characterization of mice in which transposons are mobilized in the Glial Fibrillary Acidic Protein (GFAP compartment. Glioma formation in these mice did not occur on an otherwise wild-type genetic background, but rare gliomas were observed when mobilization occurred in a p19Arf heterozygous background. Through cloning insertions from additional gliomas generated by transposon mobilization in the Rosa26 compartment, several candidate glioma genes were identified. Comparisons to genetic, epigenetic and mRNA expression data from human gliomas implicates several of these genes as tumor suppressor genes and oncogenes in human glioblastoma.

  16. Sleeping Beauty Mouse Models Identify Candidate Genes Involved in Gliomagenesis

    Science.gov (United States)

    Vyazunova, Irina; Maklakova, Vilena I.; Berman, Samuel; De, Ishani; Steffen, Megan D.; Hong, Won; Lincoln, Hayley; Morrissy, A. Sorana; Taylor, Michael D.; Akagi, Keiko; Brennan, Cameron W.; Rodriguez, Fausto J.; Collier, Lara S.

    2014-01-01

    Genomic studies of human high-grade gliomas have discovered known and candidate tumor drivers. Studies in both cell culture and mouse models have complemented these approaches and have identified additional genes and processes important for gliomagenesis. Previously, we found that mobilization of Sleeping Beauty transposons in mice ubiquitously throughout the body from the Rosa26 locus led to gliomagenesis with low penetrance. Here we report the characterization of mice in which transposons are mobilized in the Glial Fibrillary Acidic Protein (GFAP) compartment. Glioma formation in these mice did not occur on an otherwise wild-type genetic background, but rare gliomas were observed when mobilization occurred in a p19Arf heterozygous background. Through cloning insertions from additional gliomas generated by transposon mobilization in the Rosa26 compartment, several candidate glioma genes were identified. Comparisons to genetic, epigenetic and mRNA expression data from human gliomas implicates several of these genes as tumor suppressor genes and oncogenes in human glioblastoma. PMID:25423036

  17. Equilibrium models of coronal loops that involve curvature and buoyancy

    CERN Document Server

    Hindman, Bradley W

    2013-01-01

    We construct magnetostatic models of coronal loops in which the thermodynamics of the loop is fully consistent with the shape and geometry of the loop. This is achieved by treating the loop as a thin, compact, magnetic fibril that is a small departure from a force-free state. The density along the loop is related to the loop's curvature by requiring that the Lorentz force arising from this deviation is balanced by buoyancy. This equilibrium, coupled with hydrostatic balance and the ideal gas law, then connects the temperature of the loop with the curvature of the loop without resorting to a detailed treatment of heating and cooling. We present two example solutions: one with a spatially invariant magnetic Bond number (the dimensionless ratio of buoyancy to Lorentz forces) and the other with a constant radius of curvature of the loop's axis. We find that the density and temperature profiles are quite sensitive to curvature variations along the loop, even for loops with similar aspect ratios.

  18. Equilibrium Models of Coronal Loops That Involve Curvature and Buoyancy

    Science.gov (United States)

    Hindman, Bradley W.; Jain, Rekha

    2013-12-01

    We construct magnetostatic models of coronal loops in which the thermodynamics of the loop is fully consistent with the shape and geometry of the loop. This is achieved by treating the loop as a thin, compact, magnetic fibril that is a small departure from a force-free state. The density along the loop is related to the loop's curvature by requiring that the Lorentz force arising from this deviation is balanced by buoyancy. This equilibrium, coupled with hydrostatic balance and the ideal gas law, then connects the temperature of the loop with the curvature of the loop without resorting to a detailed treatment of heating and cooling. We present two example solutions: one with a spatially invariant magnetic Bond number (the dimensionless ratio of buoyancy to Lorentz forces) and the other with a constant radius of the curvature of the loop's axis. We find that the density and temperature profiles are quite sensitive to curvature variations along the loop, even for loops with similar aspect ratios.

  19. The independent spreaders involved SIR Rumor model in complex networks

    Science.gov (United States)

    Qian, Zhen; Tang, Shaoting; Zhang, Xiao; Zheng, Zhiming

    2015-07-01

    Recent studies of rumor or information diffusion process in complex networks show that in contrast to traditional comprehension, individuals who participate in rumor spreading within one network do not always get the rumor from their neighbors. They can obtain the rumor from different sources like online social networks and then publish it on their personal sites. In our paper, we discuss this phenomenon in complex networks by adopting the concept of independent spreaders. Rather than getting the rumor from neighbors, independent spreaders learn it from other channels. We further develop the classic "ignorant-spreaders-stiflers" or SIR model of rumor diffusion process in complex networks. A steady-state analysis is conducted to investigate the final spectrum of the rumor spreading under various spreading rate, stifling rate, density of independent spreaders and average degree of the network. Results show that independent spreaders effectively enhance the rumor diffusion process, by delivering the rumor to regions far away from the current rumor infected regions. And though the rumor spreading process in SF networks is faster than that in ER networks, the final size of rumor spreading in ER networks is larger than that in SF networks.

  20. A model of the supplier involvement in the product innovation

    Directory of Open Access Journals (Sweden)

    Kumar Manoj

    2017-01-01

    Full Text Available In this paper we examine the product innovation in a supply chain by a supplier and derive a model for a supplier’s product innovation policy. The product innovation of a supplier can contribute to the long-term competitiveness for the supply chain, and as it is for many supply chains a major factor, it should be considered in the development of strategies for a supplier. Here, we evaluate the effectiveness of supplier product innovation as a strategic tool to enhance the competitiveness and viability of supply chain. This paper explores the dynamic research performance of a supplier with endogenous time preference under a given arrangement of product innovation. We find that the optimal effort level and the achieved product innovation obey a saddle point path, or show tremendous fluctuations even without introducing the stochastic nature of product innovative activity. We also find that the fluctuation frequency is largely dependent both on the supplier’s characteristics such as supplier’s product innovative ability and on the nature of product innovation process per se. Short-run analyses are also made on the effect of supply chain cooperation in the product innovation process.

  1. Parents as Role Models: Parental Behavior Affects Adolescents' Plans for Work Involvement

    Science.gov (United States)

    Wiese, Bettina S.; Freund, Alexandra M.

    2011-01-01

    This study (N = 520 high-school students) investigates the influence of parental work involvement on adolescents' own plans regarding their future work involvement. As expected, adolescents' perceptions of parental work behavior affected their plans for own work involvement. Same-sex parents served as main role models for the adolescents' own…

  2. Introducing an Intervention Model for Fostering Affective Involvement with Persons Who Are Congenitally Deafblind

    Science.gov (United States)

    Martens, Marga A. W.; Janssen, Marleen J.; Ruijssenaars, Wied A. J. J. M.; Riksen-Walraven, J. Marianne

    2014-01-01

    The article presented here introduces the Intervention Model for Affective Involvement (IMAI), which was designed to train staff members (for example, teachers, caregivers, support workers) to foster affective involvement during interaction and communication with persons who have congenital deaf-blindness. The model is theoretically underpinned,…

  3. Effects of deceptive packaging and product involvement on purchase intention: an elaboration likelihood model perspective.

    Science.gov (United States)

    Lammers, H B

    2000-04-01

    From an Elaboration Likelihood Model perspective, it was hypothesized that postexposure awareness of deceptive packaging claims would have a greater negative effect on scores for purchase intention by consumers lowly involved rather than highly involved with a product (n = 40). Undergraduates who were classified as either highly or lowly (ns = 20 and 20) involved with M&Ms examined either a deceptive or non-deceptive package design for M&Ms candy and were subsequently informed of the deception employed in the packaging before finally rating their intention to purchase. As anticipated, highly deceived subjects who were low in involvement rated intention to purchase lower than their highly involved peers. Overall, the results attest to the robustness of the model and suggest that the model has implications beyond advertising effects and into packaging effects.

  4. Modeling the Relations among Parental Involvement, School Engagement and Academic Performance of High School Students

    Science.gov (United States)

    Al-Alwan, Ahmed F.

    2014-01-01

    The author proposed a model to explain how parental involvement and school engagement related to academic performance. Participants were (671) 9th and 10th graders students who completed two scales of "parental involvement" and "school engagement" in their regular classrooms. Results of the path analysis suggested that the…

  5. Public involvement in breast cancer research: an analysis and model for future research.

    Science.gov (United States)

    McCormick, Sabrina; Brody, Julia; Brown, Phil; Polk, Ruth

    2004-01-01

    Public involvement in health program planning has been taking place for many years, and has provided a precedent for the emergence of public involvement in research conducted since the early 1990s. Such involvement is now widely seen in breast cancer research, due to the large public concern and major social movement activity. This article reviews current practices and general models of public involvement in research and constructs a prototype. The authors interviewed researchers, program officers, and laypeople in order to understand the obstacles, processes, and benefits. They conclude that public involvement has major ramifications for the democratization of science and the construction of knowledge by teaching lay people about science and sensitizing researchers to concerns of the public. There is growing support on the part of scientists and government agents for public involvement.

  6. Autonomous motivation: involvement in physical activity, and perceived sport competence: structural and mediator models.

    Science.gov (United States)

    Bagøien, Tor Egil; Halvari, Hallgeir

    2005-02-01

    Students in upper secondary school (N = 231, M = 16.6 yr., SD = 1.6) were tested on involvement in physical activity, perceived sport competence, using the Perceived Competence Scale of Harter, and motivational regulation on the Self-regulation Questionnaire of Ryan and Connell. Correlations were positive among involvement in physical activity, autonomous motivation, and perceived sport competence. A hypothetical model indicated that autonomous motivation mediates the relation between perceived sport competence and involvement in physical activity. Although LISREL analysis supported this mediation, the best model fit of the data supported a structural model with involvement in physical activity (R2 = .63) to mediate between autonomous motivation and perceived competence (R2 = .47). Results are interpreted and discussed in terms of self-determination theory.

  7. Students' Involvement in Authentic Modelling Practices as Contexts in Chemistry Education

    Science.gov (United States)

    Prins, Gjalt T.; Bulte, Astrid M. W.; van Driel, Jan H.; Pilot, Albert

    2009-11-01

    In science education students should come to understand the nature and significance of models. A promising strategy to achieve this goal is using authentic modelling practices as contexts for meaningful learning of models and modelling. An authentic practice is defined as professionals working with common motives and purposes, pertaining to a similar type of procedure and applying relevant knowledge on the modelling issue they work on. In this study we evaluate whether the use of authentic practices initiates adequate students’ involvement. This was done by investigating students’ interests, ownership, familiarity and complexity. In addition, we evaluated students’ expressed modelling procedures in response to the modelling issues. We designed learning tasks which were enacted by a focus group of students. Three primary data sources were used to collect data. Firstly, a group discussion was organised in which students’ reflected on both authentic practices. Secondly, students filled in written questionnaires containing items on affective and cognitive aspects. Thirdly, the realised modelling procedures by students were analysed. The results show that students’ involvement was successfully initiated, evidenced by motivated students, willingness to continue and the completeness and quality of the realised modelling procedures. The design of the learning tasks proved to be successful in realising this involvement. The results obtained in this study support the strategy of using authentic modelling practices as contexts for meaningful learning of models and modelling.

  8. Adolescents and Music Media: Toward an Involvement-Mediational Model of Consumption and Self-Concept

    Science.gov (United States)

    Kistler, Michelle; Rodgers, Kathleen Boyce; Power, Thomas; Austin, Erica Weintraub; Hill, Laura Griner

    2010-01-01

    Using social cognitive theory and structural regression modeling, we examined pathways between early adolescents' music media consumption, involvement with music media, and 3 domains of self-concept (physical appearance, romantic appeal, and global self-worth; N=124). A mediational model was supported for 2 domains of self-concept. Music media…

  9. Does Business Model Affect CSR Involvement? A Survey of Polish Manufacturing and Service Companies

    Directory of Open Access Journals (Sweden)

    Marzanna Katarzyna Witek-Hajduk

    2016-02-01

    Full Text Available The study explores links between types of business models used by companies and their involvement in CSR. As the main part of our conceptual framework we used a business model taxonomy developed by Dudzik and Witek-Hajduk, which identifies five types of models: traditionalists, market players, contractors, distributors, and integrators. From shared characteristics of the business model profiles, we proposed that market players and integrators will show significantly higher levels of involvement in CSR than the three other classes of companies. Among other things, both market players and integrators relied strongly on building own brand value and fostering harmonious supply channel relations, which served as a rationale for our hypothesis. The data for the study were obtained through a combined CATI and CAWI survey on a group of 385 managers of medium and large enterprises. The sample was representative for the three Polish industries of chemical manufacturing, food production, and retailing. Statistical methods included confirmatory factor analysis and one-way ANOVA with contrasts and post hoc tests. The findings supported our hypothesis, showing that market players and integrators were indeed more engaged in CSR than other groups of firms. This may suggest that managers in control of these companies could bolster the integrity of their business models by increasing CSR involvement. Another important contribution of the study was to propose and validate a versatile scale for assessing CSR involvement, which showed measurement invariance for all involved industries.

  10. Customer involvement in greening the supply chain: an interpretive structural modeling methodology

    Science.gov (United States)

    Kumar, Sanjay; Luthra, Sunil; Haleem, Abid

    2013-04-01

    The role of customers in green supply chain management needs to be identified and recognized as an important research area. This paper is an attempt to explore the involvement aspect of customers towards greening of the supply chain (SC). An empirical research approach has been used to collect primary data to rank different variables for effective customer involvement in green concept implementation in SC. An interpretive structural-based model has been presented, and variables have been classified using matrice d' impacts croises- multiplication appliqué a un classement analysis. Contextual relationships among variables have been established using experts' opinions. The research may help practicing managers to understand the interaction among variables affecting customer involvement. Further, this understanding may be helpful in framing the policies and strategies to green SC. Analyzing interaction among variables for effective customer involvement in greening SC to develop the structural model in the Indian perspective is an effort towards promoting environment consciousness.

  11. A model for the occurrence and analysis of ionic thermocurrent spectrum involving different orders of kinetics

    Indian Academy of Sciences (India)

    Jai Prakash

    2013-01-01

    Ionic thermocurrent (ITC) spectrum is much similar to a thermoluminescence (TL) glow curve involving monomolecular kinetics. It has already been reported that different orders of kinetics are involved in TL processes, which depend specifically on the extent of recombination and simultaneous retrapping. It is found that the involvement of different orders of kinetics in ITC spectrum depends on the experimental conditions of polarization and rate of rapid cooling. Consequently, order of kinetics involved in the ITC spectrum does not represent any specific feature of the system under investigation. An equation is developed which explains the occurrence of ITC spectrum involving any order of kinetics. Dielectric relaxation parameters, order of kinetics and approximate number of dipoles per unit volume are evaluated conveniently and easily following the proposed model.

  12. Expanding the Work Phases Model: User and Expert Involvement in the Construction of Online Specialised Dictionaries

    DEFF Research Database (Denmark)

    Leroyer, Patrick

    The purpose of this article is to establish new proposals for the lexicographic process and the involvement of experts and users in the construction of online specialised dictionaries. It is argued that the ENeL action should also have a view to the development of innovative theories...... and methodologies for the construction of online specialised dictionaries, and a new model for user and expert involvement is proposed....

  13. Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index

    Directory of Open Access Journals (Sweden)

    Sainte-Rose Christian

    2009-04-01

    Full Text Available Abstract Background Obesity seems to be linked to the hypothalamic involvement in craniopharyngioma. We evaluated the pre-surgery relationship between the degree of this involvement on magnetic resonance imaging and insulin resistance, as evaluated by the homeostasis model insulin resistance index (HOMA. As insulin-like growth factor 1, leptin, soluble leptin receptor (sOB-R and ghrelin may also be involved, we compared their plasma concentrations and their link to weight change. Methods 27 children with craniopharyngioma were classified as either grade 0 (n = 7, no hypothalamic involvement, grade 1 (n = 8, compression without involvement, or grade 2 (n = 12, severe involvement. Results Despite having similar body mass indexes (BMI, the grade 2 patients had higher glucose, insulin and HOMA before surgery than the grade 0 (P = 0.02, The data for the whole population before and 6–18 months after surgery showed increases in BMI (P Conclusion The hypothalamic involvement by the craniopharyngioma before surgery seems to determine the degree of insulin resistance, regardless of the BMI. The pre-surgery HOMA values were correlated with the post-surgery weight gain. This suggests that obesity should be prevented by reducing inn secretion in those cases with hypothalamic involvement.

  14. Hybrid transfinite element modeling/analysis of nonlinear heat conduction problems involving phase change

    Science.gov (United States)

    Tamma, Kumar K.; Railkar, Sudhir B.

    1988-01-01

    The present paper describes the applicability of hybrid transfinite element modeling/analysis formulations for nonlinear heat conduction problems involving phase change. The methodology is based on application of transform approaches and classical Galerkin schemes with finite element formulations to maintain the modeling versatility and numerical features for computational analysis. In addition, in conjunction with the above, the effects due to latent heat are modeled using enthalpy formulations to enable a physically realistic approximation to be dealt computationally for materials exhibiting phase change within a narrow band of temperatures. Pertinent details of the approach and computational scheme adapted are described in technical detail. Numerical test cases of comparative nature are presented to demonstrate the applicability of the proposed formulations for numerical modeling/analysis of nonlinear heat conduction problems involving phase change.

  15. Petri Net Modeling of the Brain Circuit Involved in Aggressive Behavior

    OpenAIRE

    Moreno, Carlos B.; Díaz, José-Luis; Martínez, J. H.

    2015-01-01

    The purpose of this work in to demonstrate the initial results of a research project having as its goal to develop dynamic models of the brain network involved in aggressive behavior. In this way, the complex neural process correlated to basic anger emotions and resulting in aggressive behaviors is purportedly schematized by the use of Petri nets, a work-flow computational tool. Initially, the modeling technique is introduced taking into account the most recent and accepted notion of the neur...

  16. Predicting Preschoolers' Attachment Security from Fathers' Involvement, Internal Working Models, and Use of Social Support

    Science.gov (United States)

    Newland, Lisa A.; Coyl, Diana D.; Freeman, Harry

    2008-01-01

    Associations between preschoolers' attachment security, fathers' involvement (i.e. parenting behaviors and consistency) and fathering context (i.e. fathers' internal working models (IWMs) and use of social support) were examined in a subsample of 102 fathers, taken from a larger sample of 235 culturally diverse US families. The authors predicted…

  17. Helpful Components Involved in the Cognitive-Experiential Model of Dream Work

    Science.gov (United States)

    Tien, Hsiu-Lan Shelley; Chen, Shuh-Chi; Lin, Chia-Huei

    2009-01-01

    The purpose of the study was to examine the helpful components involved in the Hill's cognitive-experiential dream work model. Participants were 27 volunteer clients from colleges and universities in northern and central parts of Taiwan. Each of the clients received 1-2 sessions of dream interpretations. The cognitive-experiential dream work model…

  18. A Research Framework for Understanding the Practical Impact of Family Involvement in the Juvenile Justice System: The Juvenile Justice Family Involvement Model.

    Science.gov (United States)

    Walker, Sarah Cusworth; Bishop, Asia S; Pullmann, Michael D; Bauer, Grace

    2015-12-01

    Family involvement is recognized as a critical element of service planning for children's mental health, welfare and education. For the juvenile justice system, however, parents' roles in this system are complex due to youths' legal rights, public safety, a process which can legally position parents as plaintiffs, and a historical legacy of blaming parents for youth indiscretions. Three recent national surveys of juvenile justice-involved parents reveal that the current paradigm elicits feelings of stress, shame and distrust among parents and is likely leading to worse outcomes for youth, families and communities. While research on the impact of family involvement in the justice system is starting to emerge, the field currently has no organizing framework to guide a research agenda, interpret outcomes or translate findings for practitioners. We propose a research framework for family involvement that is informed by a comprehensive review and content analysis of current, published arguments for family involvement in juvenile justice along with a synthesis of family involvement efforts in other child-serving systems. In this model, family involvement is presented as an ascending, ordinal concept beginning with (1) exclusion, and moving toward climates characterized by (2) information-giving, (3) information-eliciting and (4) full, decision-making partnerships. Specific examples of how courts and facilities might align with these levels are described. Further, the model makes predictions for how involvement will impact outcomes at multiple levels with applications for other child-serving systems.

  19. A devolved model for public involvement in the field of mental health research: case study learning.

    Science.gov (United States)

    Moule, Pam; Davies, Rosie

    2016-12-01

    Patient and public involvement in all aspects of research is espoused and there is a continued interest in understanding its wider impact. Existing investigations have identified both beneficial outcomes and remaining issues. This paper presents the impact of public involvement in one case study led by a mental health charity conducted as part of a larger research project. The case study used a devolved model of working, contracting with service user-led organizations to maximize the benefits of local knowledge on the implementation of personalized budgets, support recruitment and local user-led organizations. To understand the processes and impact of public involvement in a devolved model of working with user-led organizations. Multiple data collection methods were employed throughout 2012. These included interviews with the researchers (n = 10) and research partners (n = 5), observation of two case study meetings and the review of key case study documentation. Analysis was conducted in NVivo10 using a coding framework developed following a literature review. Five key themes emerged from the data; Devolved model, Nature of involvement, Enabling factors, Implementation challenges and Impact. While there were some challenges of implementing the devolved model it is clear that our findings add to the growing understanding of the positive benefits research partners can bring to complex research. A devolved model can support the involvement of user-led organizations in research if there is a clear understanding of the underpinning philosophy and support mechanisms are in place. © 2015 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

  20. Selection Model of Optional Parts in Suppliers Involved in New Product Development

    Institute of Scientific and Technical Information of China (English)

    MU Lifeng; TANG Jiafu; PAN Zhendong; HAN Yi

    2006-01-01

    Quality function deployment (QFD), which can translate efficiently customer requirement (CRs) into technical attributes (TAs), is widely used in new product development (NPD) as an efficient customer-driven approach. After lots of QFD application is applied in manufacturing fields, it was proved that without considering suppliers involved, it is difficult to get precise and satisfying results in each process of QFD, particularly part deployment. The paper will address the issues of a model of optional parts selection in suppliers involved in part deployment process. Further, it has been applied to an ERP system reconstruction and updating problem as an illustration.

  1. Opioid receptor types involved in the development of nicotine physical dependence in an invertebrate (Planaria) model.

    Science.gov (United States)

    Raffa, Robert B; Baron, Steve; Bhandal, Jaspreet S; Brown, Tevin; Song, Kevin; Tallarida, Christopher S; Rawls, Scott M

    2013-11-01

    Recent data suggest that opioid receptors are involved in the development of nicotine physical dependence in mammals. Evidence in support of a similar involvement in an invertebrate (Planaria) is presented using the selective opioid receptor antagonist naloxone, and the more receptor subtype-selective antagonists CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) (μ, MOR), naltrindole (δ, DOR), and nor-BNI (norbinaltorphimine) (κ, KOR). Induction of physical dependence was achieved by 60-min pre-exposure of planarians to nicotine and was quantified by abstinence-induced withdrawal (reduction in spontaneous locomotor activity). Known MOR and DOR subtype-selective opioid receptor antagonists attenuated the withdrawal, as did the non-selective antagonist naloxone, but a KOR subtype-selective antagonist did not. An involvement of MOR and DOR, but not KOR, in the development of nicotine physical dependence or in abstinence-induced withdrawal was thus demonstrated in a sensitive and facile invertebrate model.

  2. A homology model of Xyloglucan Xylosyltransferase 2 reveals critical amino acids involved in substrate binding.

    Science.gov (United States)

    Culbertson, Alan T; Tietze, Alesia A; Tietze, Daniel; Chou, Yi-Hsiang; Smith, Adrienne L; Young, Zachary T; Zabotina, Olga A

    2016-09-01

    In dicotyledonous plants, xyloglucan (XyG) is the most abundant hemicellulose of the primary cell wall. The enzymes involved in XyG biosynthesis have been identified through reverse-genetics and activity was characterized by heterologous expression. Currently, there is no information on the atomic structures or amino acids involved in activity or substrate binding of any of the Golgi-localized XyG biosynthetic enzymes. A homology model of the xyloglucan xylosyltransferase 2 (XXT2) catalytic domain was built on the basis of the crystal structure of A64Rp. Molecular dynamics simulations revealed that the homology model retains the glycosyltransferase (GT)-A fold of the template structure used to build the homology model indicating that XXT2 likely has a GT-A fold. According to the XXT2 homology model, six amino acids (Phe204, Lys207, Asp228, Ser229, Asp230, His378) were selected and their contribution in catalytic activity was investigated. Site-directed mutagenesis studies show that Asp228, Asp230 and His378 are critical for XXT2 activity and are predicted to be involved in coordination of manganese ion. Lys207 was also found to be critical for protein activity and the homology model indicates a critical role in substrate binding. Additionally, Phe204 mutants have less of an impact on XXT2 activity with the largest effect when replaced with a polar residue. This is the first study that investigates the amino acids involved in substrate binding of the XyG-synthesizing xylosyltransferases and contributes to the understanding of the mechanisms of polysaccharide-synthesizing GTs and XyG biosynthesis. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Evaluation of vehicle damage involved in road crashes based on quantificated model

    Institute of Scientific and Technical Information of China (English)

    FAN Yan-hui; XU Hong-guo; JIANG Hua-ping

    2008-01-01

    Based on economics theory, social value loss caused by vehicle involved in crashes as well as various factors influencing on it were analyzed, the corresponding micro-econometrics model was theoretically given. Moreover, the practicability of the model,the veracity and rationality of quantification were analyzed. Based on probability theory and mathematical statistical theory, macro approach to evaluating vehicle damage in crashes was presented, and the corresponding macro-econometrics model was constructed. In addition, the macro-econometrics model was utilized to assess economic loss from statistical data of vehicle damaged in crashes, which has shown that the model can meet the demand of quantification analysis of vehicle damage, and be applied to the evaluation of economic loss caused by crashes. The results in this paper will be of practical significance for scientific, comprehensive and rational evaluating socio-economic loss caused by road crashes.

  4. Degree of multicollinearity and variables involved in linear dependence in additive-dominant models

    Directory of Open Access Journals (Sweden)

    Juliana Petrini

    2012-12-01

    Full Text Available The objective of this work was to assess the degree of multicollinearity and to identify the variables involved in linear dependence relations in additive-dominant models. Data of birth weight (n=141,567, yearling weight (n=58,124, and scrotal circumference (n=20,371 of Montana Tropical composite cattle were used. Diagnosis of multicollinearity was based on the variance inflation factor (VIF and on the evaluation of the condition indexes and eigenvalues from the correlation matrix among explanatory variables. The first model studied (RM included the fixed effect of dam age class at calving and the covariates associated to the direct and maternal additive and non-additive effects. The second model (R included all the effects of the RM model except the maternal additive effects. Multicollinearity was detected in both models for all traits considered, with VIF values of 1.03 - 70.20 for RM and 1.03 - 60.70 for R. Collinearity increased with the increase of variables in the model and the decrease in the number of observations, and it was classified as weak, with condition index values between 10.00 and 26.77. In general, the variables associated with additive and non-additive effects were involved in multicollinearity, partially due to the natural connection between these covariables as fractions of the biological types in breed composition.

  5. Portraiture of constructivist parental involvement: A model to develop a community of practice

    Science.gov (United States)

    Dignam, Christopher Anthony

    This qualitative research study addressed the problem of the lack of parental involvement in secondary school science. Increasing parental involvement is vital in supporting student academic achievement and social growth. The purpose of this emergent phenomenological study was to identify conditions required to successfully construct a supportive learning environment to form partnerships between students, parents, and educators. The overall research question in this study investigated the conditions necessary to successfully enlist parental participation with students during science inquiry investigations at the secondary school level. One hundred thirteen pairs of parents and students engaged in a 6-week scientific inquiry activity and recorded attitudinal data in dialogue journals, questionnaires, open-ended surveys, and during one-one-one interviews conducted by the researcher between individual parents and students. Comparisons and cross-interpretations of inter-rater, codified, triangulated data were utilized for identifying emergent themes. Data analysis revealed the active involvement of parents in researching with their child during inquiry investigations, engaging in journaling, and assessing student performance fostered partnerships among students, parents, and educators and supported students' social skills development. The resulting model, employing constructivist leadership and enlisting parent involvement, provides conditions and strategies required to develop a community of practice that can help effect social change. The active involvement of parents fostered improved efficacy and a holistic mindset to develop in parents, students, and teachers. Based on these findings, the interactive collaboration of parents in science learning activities can proactively facilitate a community of practice that will assist educators in facilitating social change.

  6. Involving the elderly in the design process: a participatory design model for usability, safety and attractiveness

    OpenAIRE

    Demirbilek, Oya

    1999-01-01

    Ankara : Institute of Economics and Social Sciences of Bilkent University, 1999. Thesis (Ph.D.) -- Bilkent University, 1999 Includes bibliographical references leaves 113-131 This work presents a conceptual model involving the elderly users into the design process by means of participatory design sessions, where the expertise of designers and the real requirements and opinions of elderly end-users, related to how objects, environments and equipment should be designed to allow ageing ...

  7. Semi-Implicit Algorithm for Elastoplastic Damage Models Involving Energy Integration

    OpenAIRE

    Ji Zhang; Jie Li

    2016-01-01

    This study aims to develop a semi-implicit constitutive integration algorithm for a class of elastoplastic damage models where calculation of damage energy release rates involves integration of free energy. The constitutive equations with energy integration are split into the elastic predictor, plastic corrector, and damage corrector. The plastic corrector is solved with an improved format of the semi-implicit spectral return mapping, which is characterized by constant flow direction and plas...

  8. Development of a Gravid Uterus Model for the Study of Road Accidents Involving Pregnant Women.

    Science.gov (United States)

    Auriault, F; Thollon, L; Behr, M

    2016-01-01

    Car accident simulations involving pregnant women are well documented in the literature and suggest that intra-uterine pressure could be responsible for the phenomenon of placental abruption, underlining the need for a realistic amniotic fluid model, including fluid-structure interactions (FSI). This study reports the development and validation of an amniotic fluid model using an Arbitrary Lagrangian Eulerian formulation in the LS-DYNA environment. Dedicated to the study of the mechanisms responsible for fetal injuries resulting from road accidents, the fluid model was validated using dynamic loading tests. Drop tests were performed on a deformable water-filled container at acceleration levels that would be experienced in a gravid uterus during a frontal car collision at 25 kph. During the test device braking phase, container deformation induced by inertial effects and FSI was recorded by kinematic analysis. These tests were then simulated in the LS-DYNA environment to validate a fluid model under dynamic loading, based on the container deformations. Finally, the coupling between the amniotic fluid model and an existing finite-element full-body pregnant woman model was validated in terms of pressure. To do so, experimental test results performed on four postmortem human surrogates (PMHS) (in which a physical gravid uterus model was inserted) were used. The experimental intra-uterine pressure from these tests was compared to intra uterine pressure from a numerical simulation performed under the same loading conditions. Both free fall numerical and experimental responses appear strongly correlated. The relationship between the amniotic fluid model and pregnant woman model provide intra-uterine pressure values correlated with the experimental test responses. The use of an Arbitrary Lagrangian Eulerian formulation allows the analysis of FSI between the amniotic fluid and the gravid uterus during a road accident involving pregnant women.

  9. Molecular modelling of S-RNases involved in almond self-incompatibility

    Directory of Open Access Journals (Sweden)

    Angel eFernandez i Marti

    2012-06-01

    Full Text Available Gametophytic self-incompatibility (GSI is a mechanism in flowering plants, to prevent inbreeding and promote outcrossing. GSI is under the control of a specific locus, known as the S-locus, which contains at least two genes, the RNase and the SFB. Active S-RNases in the style are essential for rejection of haploid pollen, when the pollen S-allele matches one of two S-alleles of the diploid pistil. However, the nature of their mutual interactions at genetic and biochemical levels remain unclear. Thus, detailed understanding of the protein structure involved in GSI may help in discovering how the proteins involved in GSI may function and how they fulfil their biological roles. To this end, 3D models of the SC (Sf and two SI (S8 and S23 S-RNases of almond were constructed, using comparative modelling tools. The modelled structures consisted of mixed α and β folds, with six helices and six beta-strands. However, the self-compatible (Sf RNase contained an additional extended loop between the conserved domains RC4 and C5, which may be involved in the manifestation of self-compatibility in almond.

  10. System Model Bias Processing Approach for Regional Coordinated States Information Involved Filtering

    Directory of Open Access Journals (Sweden)

    Zebo Zhou

    2016-01-01

    Full Text Available In the Kalman filtering applications, the conventional dynamic model which connects the states information of two consecutive epochs by state transition matrix is usually predefined and assumed to be invariant. Aiming to improve the adaptability and accuracy of dynamic model, we propose multiple historical states involved filtering algorithm. An autoregressive model is used as the dynamic model which is subsequently combined with observation model for deriving the optimal window-recursive filter formulae in the sense of minimum mean square error principle. The corresponding test statistics characteristics of system residuals are discussed in details. The test statistics of regional predicted residuals are then constructed in a time-window for model bias testing with two hypotheses, that is, the null and alternative hypotheses. Based on the innovations test statistics, we develop a model bias processing procedure including bias detection, location identification, and state correction. Finally, the minimum detectable bias and bias-to-noise ratio are both computed for evaluating the internal and external reliability of overall system, respectively.

  11. Pore scale modeling of reactive transport involved in geologic CO2 sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Qinjin [Los Alamos National Laboratory; Lichtner, Peter C [Los Alamos National Laboratory; Viswanathan, Hari S [Los Alamos National Laboratory; Abdel-fattah, Amr I [Los Alamos National Laboratory

    2009-01-01

    We apply a multi-component reactive transport lattice Boltzmann model developed in previolls studies to modeling the injection of a C02 saturated brine into various porous media structures at temperature T=25 and 80 C. The porous media are originally consisted of calcite. A chemical system consisting of Na+, Ca2+, Mg2+, H+, CO2(aq), and CI-is considered. The fluid flow, advection and diHusion of aqueous species, homogeneous reactions occurring in the bulk fluid, as weB as the dissolution of calcite and precipitation of dolomite are simulated at the pore scale. The effects of porous media structure on reactive transport are investigated. The results are compared with continuum scale modeling and the agreement and discrepancy are discussed. This work may shed some light on the fundamental physics occurring at the pore scale for reactive transport involved in geologic C02 sequestration.

  12. Model correction factor method for reliability problems involving integrals of non-Gaussian random fields

    DEFF Research Database (Denmark)

    Franchin, P.; Ditlevsen, Ove Dalager; Kiureghian, Armen Der

    2002-01-01

    The model correction factor method (MCFM) is used in conjunction with the first-order reliability method (FORM) to solve structural reliability problems involving integrals of non-Gaussian random fields. The approach replaces the limit-state function with an idealized one, in which the integrals...... are considered to be Gaussian. Conventional FORM analysis yields the linearization point of the idealized limit-state surface. A model correction factor is then introduced to push the idealized limit-state surface onto the actual limit-state surface. A few iterations yield a good approximation of the reliability...... reliability method; Model correction factor method; Nataf field integration; Non-Gaussion random field; Random field integration; Structural reliability; Pile foundation reliability...

  13. Modelling binaural processes involved in simultaneous reflection masking: limitations of current models

    DEFF Research Database (Denmark)

    Buchholz, Jörg

    2007-01-01

    Masked thresholds were measured for a single test reflection, masked by the direct sound, as a function of the reflection delay. This was done for diotic as well as for dichotic stimulus presentations and all stimuli were presented via headphones. The input signal was a 200-ms long broadband noise....... The dichotic threshold decreased with increasing reflection delay indicating an increase in binaural detection performance with increasing reflection delay. Comparing the dichotic threshold to the corresponding diotic threshold, for delays below 7-10 ms, the dichotic threshold was found to be higher than...... the diotic threshold while it was lower than the diotic threshold for larger delays. Hence, the binaural system seems to deteriorate auditory detection performance for very early reflections and to enhance auditory detection performance for later reflections. Existing binaural (detection) models...

  14. Modelling of phase equilibria and related properties of mixtures involving lipids

    DEFF Research Database (Denmark)

    Cunico, Larissa

    Many challenges involving physical and thermodynamic properties in the production of edible oils and biodiesel are observed, such as availability of experimental data and realiable prediction. In the case of lipids, a lack of experimental data for pure components and also for their mixtures in open...... literature was observed, what makes it necessary to development reliable predictive models from limited data. One of the first steps of this project was the creation of a database containing properties of mixtures involved in tasks related to process design, simulation, and optimization as well as design...... of chemicals based products. This database was combined with the existing lipids database of pure component properties. To contribute to the missing data, measurements of isobaric vapour-liquid equilibrium (VLE) data of two binary mixtures at two different pressures were performed using Differential Scanning...

  15. A comparative modeling and molecular docking study on Mycobacterium tuberculosis targets involved in peptidoglycan biosynthesis.

    Science.gov (United States)

    Fakhar, Zeynab; Naiker, Suhashni; Alves, Claudio N; Govender, Thavendran; Maguire, Glenn E M; Lameira, Jeronimo; Lamichhane, Gyanu; Kruger, Hendrik G; Honarparvar, Bahareh

    2016-11-01

    An alarming rise of multidrug-resistant Mycobacterium tuberculosis strains and the continuous high global morbidity of tuberculosis have reinvigorated the need to identify novel targets to combat the disease. The enzymes that catalyze the biosynthesis of peptidoglycan in M. tuberculosis are essential and noteworthy therapeutic targets. In this study, the biochemical function and homology modeling of MurI, MurG, MraY, DapE, DapA, Alr, and Ddl enzymes of the CDC1551 M. tuberculosis strain involved in the biosynthesis of peptidoglycan cell wall are reported. Generation of the 3D structures was achieved with Modeller 9.13. To assess the structural quality of the obtained homology modeled targets, the models were validated using PROCHECK, PDBsum, QMEAN, and ERRAT scores. Molecular dynamics simulations were performed to calculate root mean square deviation (RMSD) and radius of gyration (Rg) of MurI and MurG target proteins and their corresponding templates. For further model validation, RMSD and Rg for selected targets/templates were investigated to compare the close proximity of their dynamic behavior in terms of protein stability and average distances. To identify the potential binding mode required for molecular docking, binding site information of all modeled targets was obtained using two prediction algorithms. A docking study was performed for MurI to determine the potential mode of interaction between the inhibitor and the active site residues. This study presents the first accounts of the 3D structural information for the selected M. tuberculosis targets involved in peptidoglycan biosynthesis.

  16. Investigation of pulmonary involvement in inflammatory bowel disease in an experimental model of colitis.

    Science.gov (United States)

    Aydin, Bunyamin; Songur, Yıldıran; Songur, Necla; Aksu, Oğuzhan; Senol, Altug; Ciris, I Metin; Sutcu, Recep

    2016-09-01

    Inflammatory bowel disease (IBD) may also involve various extra-intestinal organs. Clinical studies have found asymptomatic/symptomatic pulmonary involvement in 1% to 6% of patients with IBD. The present study histopathologically investigated pulmonary involvement in an experimental model of colitis in order to demonstrate pulmonary tissue involvement in IBD and to expose potential etiological factors. It also explored the relation between inflammation and tissue concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α). The study comprised 24 male Wistar albino rats. The rats were divided into four groups of six rats each. Acute colitis was induced in two separate groups using either the dextran sulphate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) method, while the other two groups were used as controls for each model of colitis. Wallace scoring was used for macroscopic assessment of colitis, and the lungs were histopathologically examined. Concentrations of VEGF and TNF-α in pulmonary tissue were measured by the enzyme-linked immunosorbent assay method. The number of animals that had alveolar hemorrhage was significantly higher in the TNBS-induced colitis and DSS-induced colitis groups compared to their own control groups (p = 0.015 and p = 0.015, respectively). VEGF and TNF-α concentrations in pulmonary tissues were significantly increased in both the TNBS colitis and DSS colitis groups compared to their own control groups (p = 0.002 and p = 0.004, respectively; and p = 0.002 and p = 0.002, respectively). The present study demonstrated that significant and serious histopathological changes directly associated with colitis occur in the lungs in IBD.

  17. Investigation of pulmonary involvement in inflammatory bowel disease in an experimental model of colitis

    Science.gov (United States)

    Aydin, Bunyamin; Songur, Yıldıran; Songur, Necla; Aksu, Oğuzhan; Senol, Altug; Ciris, I. Metin; Sutcu, Recep

    2016-01-01

    Background/Aims: Inflammatory bowel disease (IBD) may also involve various extra-intestinal organs. Clinical studies have found asymptomatic/symptomatic pulmonary involvement in 1% to 6% of patients with IBD. The present study histopathologically investigated pulmonary involvement in an experimental model of colitis in order to demonstrate pulmonary tissue involvement in IBD and to expose potential etiological factors. It also explored the relation between inflammation and tissue concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α). Methods: The study comprised 24 male Wistar albino rats. The rats were divided into four groups of six rats each. Acute colitis was induced in two separate groups using either the dextran sulphate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) method, while the other two groups were used as controls for each model of colitis. Wallace scoring was used for macroscopic assessment of colitis, and the lungs were histopathologically examined. Concentrations of VEGF and TNF-α in pulmonary tissue were measured by the enzyme-linked immunosorbent assay method. Results: The number of animals that had alveolar hemorrhage was significantly higher in the TNBS-induced colitis and DSS-induced colitis groups compared to their own control groups (p = 0.015 and p = 0.015, respectively). VEGF and TNF-α concentrations in pulmonary tissues were significantly increased in both the TNBS colitis and DSS colitis groups compared to their own control groups (p = 0.002 and p = 0.004, respectively; and p = 0.002 and p = 0.002, respectively). Conclusions: The present study demonstrated that significant and serious histopathological changes directly associated with colitis occur in the lungs in IBD. PMID:27539446

  18. University Physics Students' Use of Models in Explanations of Phenomena Involving Interaction between Metals and Electromagnetic Radiation.

    Science.gov (United States)

    Redfors, Andreas; Ryder, Jim

    2001-01-01

    Examines third year university physics students' use of models when explaining familiar phenomena involving interaction between metals and electromagnetic radiation. Concludes that few students use a single model consistently. (Contains 27 references.) (DDR)

  19. Modelling and pathway identification involving the transport mechanism of a complex metabolic system in batch culture

    Science.gov (United States)

    Yuan, Jinlong; Zhang, Xu; Zhu, Xi; Feng, Enmin; Yin, Hongchao; Xiu, Zhilong

    2014-06-01

    The bio-dissimilation of glycerol to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae (K. pneumoniae) can be characterized by a complex metabolic system of interactions among biochemical fluxes, metabolic compounds, key enzymes and genetic regulation. In this paper, in consideration of the fact that the transport ways of 1,3-PD and glycerol with different weights across cell membrane are still unclear in batch culture, we consider 121 possible metabolic pathways and establish a novel mathematical model which is represented by a complex metabolic system. Taking into account the difficulty in accurately measuring the concentration of intracellular substances and the absence of equilibrium point for the metabolic system of batch culture, the novel approach used here is to define quantitatively biological robustness of the intracellular substance concentrations for the overall process of batch culture. To determine the most possible metabolic pathway, we take the defined biological robustness as cost function and establish an identification model, in which 1452 system parameters and 484 pathway parameters are involved. Simultaneously, the identification model is subject to the metabolic system, continuous state constraints and parameter constraints. As such, solving the identification model by a serial program is a very complicated task. We propose a parallel migration particle swarm optimization algorithm (MPSO) capable of solving the identification model in conjunction with the constraint transcription and smoothing approximation techniques. Numerical results show that the most possible metabolic pathway and the corresponding metabolic system can reasonably describe the process of batch culture.

  20. Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection

    Science.gov (United States)

    Anderson, Christopher S.; DeDiego, Marta L.; Topham, David J.; Thakar, Juilee

    2016-01-01

    Systems virology integrates host-directed approaches with molecular profiling to understand viral pathogenesis. Self-contained statistical approaches that combine expression profiles of genes with the available databases defining the genes involved in the pathways (gene-sets) have allowed characterization of predictive gene-signatures associated with outcome of the influenza virus (IV) infection. However, such enrichment techniques do not take into account interactions among pathways that are responsible for the IV infection pathogenesis. We investigate dendritic cell response to seasonal H1N1 influenza A/New Caledonia/20/1999 (NC) infection and infer the Boolean logic rules underlying the interaction network of ligand induced signaling pathways and transcription factors. The model reveals several novel regulatory modes and provides insights into mechanism of cross talk between NFκB and IRF mediated signaling. Additionally, the logic rule underlying the regulation of IL2 pathway that was predicted by the Boolean model was experimentally validated. Thus, the model developed in this paper integrates pathway analysis tools with the dynamic modeling approaches to reveal the regulation between signaling pathways and transcription factors using genome-wide transcriptional profiles measured upon influenza infection. PMID:26981147

  1. Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection

    Directory of Open Access Journals (Sweden)

    Christopher S. Anderson

    2016-01-01

    Full Text Available Systems virology integrates host-directed approaches with molecular profiling to understand viral pathogenesis. Self-contained statistical approaches that combine expression profiles of genes with the available databases defining the genes involved in the pathways (gene-sets have allowed characterization of predictive gene-signatures associated with outcome of the influenza virus (IV infection. However, such enrichment techniques do not take into account interactions among pathways that are responsible for the IV infection pathogenesis. We investigate dendritic cell response to seasonal H1N1 influenza A/New Caledonia/20/1999 (NC infection and infer the Boolean logic rules underlying the interaction network of ligand induced signaling pathways and transcription factors. The model reveals several novel regulatory modes and provides insights into mechanism of cross talk between NFκB and IRF mediated signaling. Additionally, the logic rule underlying the regulation of IL2 pathway that was predicted by the Boolean model was experimentally validated. Thus, the model developed in this paper integrates pathway analysis tools with the dynamic modeling approaches to reveal the regulation between signaling pathways and transcription factors using genome-wide transcriptional profiles measured upon influenza infection.

  2. Boolean Modeling of Cellular and Molecular Pathways Involved in Influenza Infection.

    Science.gov (United States)

    Anderson, Christopher S; DeDiego, Marta L; Topham, David J; Thakar, Juilee

    2016-01-01

    Systems virology integrates host-directed approaches with molecular profiling to understand viral pathogenesis. Self-contained statistical approaches that combine expression profiles of genes with the available databases defining the genes involved in the pathways (gene-sets) have allowed characterization of predictive gene-signatures associated with outcome of the influenza virus (IV) infection. However, such enrichment techniques do not take into account interactions among pathways that are responsible for the IV infection pathogenesis. We investigate dendritic cell response to seasonal H1N1 influenza A/New Caledonia/20/1999 (NC) infection and infer the Boolean logic rules underlying the interaction network of ligand induced signaling pathways and transcription factors. The model reveals several novel regulatory modes and provides insights into mechanism of cross talk between NFκB and IRF mediated signaling. Additionally, the logic rule underlying the regulation of IL2 pathway that was predicted by the Boolean model was experimentally validated. Thus, the model developed in this paper integrates pathway analysis tools with the dynamic modeling approaches to reveal the regulation between signaling pathways and transcription factors using genome-wide transcriptional profiles measured upon influenza infection.

  3. Integrated supply chain inventory model with quality improvement involving controllable lead time and backorder price discount

    Directory of Open Access Journals (Sweden)

    Prashant Jindal

    2016-06-01

    Full Text Available For the past four decades the integrated vendor and buyer supply chain inventory model has been an interesting topic, but quality improvement of defective items in the integrated inventory model with backorder price discount involving controllable lead time has been rarely discussed. The aim of this paper is to minimize the total related cost in the continuous review model by considering the order quantity, reorder point, lead time, process quality, backorder price discount and number of shipment as decision variables. Moreover, we assume that an investment function is used to improve the process quality. The lead time demand follows a normal distribution. In addition, the buyer offers backorder price discount to motivate the customers for possible backorders. There are some defective items in the arrival lot, so its treatment is also taken in account in this paper. We develop an iterative procedure for finding the optimal values of decision variables and numerical example is presented to illustrate the solution procedure. Additionally, sensitivity analysis with respect to major parameters is also carried out.

  4. Cadmium Handling, Toxicity and Molecular Targets Involved during Pregnancy: Lessons from Experimental Models

    Science.gov (United States)

    Santoyo-Sánchez, Mitzi; Thévenod, Frank; Barbier, Olivier

    2017-01-01

    Even decades after the discovery of Cadmium (Cd) toxicity, research on this heavy metal is still a hot topic in scientific literature: as we wrote this review, more than 1440 scientific articles had been published and listed by the PubMed.gov website during 2017. Cadmium is one of the most common and harmful heavy metals present in our environment. Since pregnancy is a very particular physiological condition that could impact and modify essential pathways involved in the handling of Cd, the prenatal life is a critical stage for exposure to this non-essential element. To give the reader an overview of the possible mechanisms involved in the multiple organ toxic effects in fetuses after the exposure to Cd during pregnancy, we decided to compile some of the most relevant experimental studies performed in experimental models and to summarize the advances in this field such as the Cd distribution and the factors that could alter it (diet, binding-proteins and membrane transporters), the Cd-induced toxicity in dams (preeclampsia, fertility, kidney injury, alteration in essential element homeostasis and bone mineralization), in placenta and in fetus (teratogenicity, central nervous system, liver and kidney). PMID:28737682

  5. Social Recovery Model: An 8-Year Investigation of Adolescent 12-step Group Involvement following Inpatient Treatment

    Science.gov (United States)

    Kelly, John F.; Brown, Sandra A.; Abrantes, Ana; Kahler, Christopher; Myers, Mark

    2013-01-01

    Background Despite widespread use of 12-step treatment approaches and referrals to Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) by youth providers, little is known about the significance of these organizations in youth addiction recovery. Furthermore, existing evidence is based mostly on short-term follow-up and is limited methodologically. Methods Adolescent inpatients (N = 160; M age = 16, 40% female) were followed at 6-months, and at 1, 2, 4, 6, and 8 years post-treatment. Time-lagged, generalized estimating equations (GEE) modeled treatment outcome in relation to AA/NA attendance controlling for static and time-varying covariates. Robust regression (LOWESS) explored dose-response thresholds of AA/NA attendance on outcome. Results AA/NA attendance was common and intensive early post-treatment, but declined sharply and steadily over the 8-year period. Patients with greater addiction severity and those who believed they could not use substances in moderation were more likely to attend. Despite declining attendance, the effects related to AA/NA remained significant and consistent. Greater early participation was associated with better long-term outcomes. Conclusions Even though many youth discontinue AA/NA over time, attendees appear to benefit, and more severely substance-involved youth attend most. Successful early post-treatment engagement of youth in abstinence-supportive social contexts, such as AA/NA, may have long-term implications for alcohol and drug involvement into young adulthood. PMID:18557829

  6. The emission of α,ω-diphenylpolyenes: A model involving several molecular structures

    Science.gov (United States)

    Catalán, Javier

    2007-05-01

    Available photophysical evidence for the emission of α,ω-diphenylpolyenes is shown to be consistent with a previously reported model [J. Catalán, J.L.G. de Paz, J. Chem. Phys. 124 (2006) 034306] involving two electronically excited molecular structures of 1B u and C s symmetry, respectively. The 1B u structure is produced by direct light absorption from the all- trans form of the α,ω-diphenylpolyene in the ground state and its emission exhibits mirror symmetry with respect to the absorption of the compound. On the other hand, the C s structure is generated from the 1B u structure of the α,ω-diphenylpolyene by rotation about a C-C single bond in the polyene chain, its emission being red-shifted with respect to the previous one and exhibiting markedly decreased vibrational structure. At room temperature, both emissions give the excitation spectrum, which are ascribed to the first absorption band for the compound. It is shown that some polyenes may exist in more than one structure of C s symmetry in the excited electronic state with lower energy than that of the 1B u state, from which the C s structures are produced. Hence, more than one electronic structure may be involved in the deactivation processes of the 1B u state, which is initially populated upon photo-excitation of the polyene molecule in the ground electronic state.

  7. An EMQ inventory model for defective products involving rework and sales team's initiatives-dependent demand

    Science.gov (United States)

    Priyan, S.; Uthayakumar, R.

    2015-07-01

    This paper investigates the issue of an economic manufacturing quantity model for defective products involving imperfect production processes and rework. We consider that the demand is sensitive to promotional efforts/sales teams' initiatives as well as the setup cost can be reduced through further investment. It also assumes that fixed quantity multiple installments of the finished batch are delivered to customers at a fixed interval of time. The long-run average cost function is derived and its convexity is proved via differential calculus. An effective iterative solution procedure is developed to achieve optimal replenishment lot-size, setup cost and the initiatives of sales teams so that the total cost of system is minimized. Numerical and sensitivity analyses are performed to evaluate the outcome of the proposed solution procedure presented in this research.

  8. System Dynamics Modelling of the Processes Involving the Maintenance of the Naive T Cell Repertoire

    CERN Document Server

    Figueredo, Grazziela P; Whitbrook, Amanda

    2010-01-01

    The study of immune system aging, i.e. immunosenescence, is a relatively new research topic. It deals with understanding the processes of immunodegradation that indicate signs of functionality loss possibly leading to death. Even though it is not possible to prevent immunosenescence, there is great benefit in comprehending its causes, which may help to reverse some of the damage done and thus improve life expectancy. One of the main factors influencing the process of immunosenescence is the number and phenotypical variety of naive T cells in an individual. This work presents a review of immunosenescence, proposes system dynamics modelling of the processes involving the maintenance of the naive T cell repertoire and presents some preliminary results.

  9. Processes and parameters involved in modeling radionuclide transport from bedded salt repositories. Final report. Technical memorandum

    Energy Technology Data Exchange (ETDEWEB)

    Evenson, D.E.; Prickett, T.A.; Showalter, P.A.

    1979-07-01

    The parameters necessary to model radionuclide transport in salt beds are identified and described. A proposed plan for disposal of the radioactive wastes generated by nuclear power plants is to store waste canisters in repository sites contained in stable salt formations approximately 600 meters below the ground surface. Among the principal radioactive wastes contained in these canisters will be radioactive isotopes of neptunium, americium, uranium, and plutonium along with many highly radioactive fission products. A concern with this form of waste disposal is the possibility of ground-water flow occurring in the salt beds and endangering water supplies and the public health. Specifically, the research investigated the processes involved in the movement of radioactive wastes from the repository site by groundwater flow. Since the radioactive waste canisters also generate heat, temperature is an important factor. Among the processes affecting movement of radioactive wastes from a repository site in a salt bed are thermal conduction, groundwater movement, ion exchange, radioactive decay, dissolution and precipitation of salt, dispersion and diffusion, adsorption, and thermomigration. In addition, structural changes in the salt beds as a result of temperature changes are important. Based upon the half-lives of the radioactive wastes, he period of concern is on the order of a million years. As a result, major geologic phenomena that could affect both the salt bed and groundwater flow in the salt beds was considered. These phenomena include items such as volcanism, faulting, erosion, glaciation, and the impact of meteorites. CDM reviewed all of the critical processes involved in regional groundwater movement of radioactive wastes and identified and described the parameters that must be included to mathematically model their behavior. In addition, CDM briefly reviewed available echniques to measure these parameters.

  10. Involvement of EphB1 receptors signalling in models of inflammatory and neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Vincent Cibert-Goton

    Full Text Available EphB receptors tyrosine kinases and ephrinB ligands were first identified as guidance molecules involved in the establishment of topographical mapping and connectivity in the nervous system during development. Later in development and into adulthood their primary role would switch from guidance to activity-dependent modulation of synaptic efficacy. In sensory systems, they play a role in both the onset of inflammatory and neuropathic pain, and in the establishment of central sensitisation, an NMDA-mediated form of synaptic plasticity thought to underlie most forms of chronic pain. We studied wild type and EphB1 knockout mice in a range of inflammatory and neuropathic pain models to determine 1, whether EphB1 expression is necessary for the onset and/or maintenance of persistent pain, regardless of origin; 2, whether in these models cellular and molecular changes, e.g. phosphorylation of the NR2B subunit of the NMDA receptor, increased c-fos expression or microglial activation, associated with the onset of pain, are affected by the lack of functional EphB1 receptors. Differences in phenotype were examined behaviourally, anatomically, biochemically and electrophysiologically. Our results establish firstly, that functional EphB1 receptors are not essential for the development of normal nociception, thermal or mechanical sensitivity. Secondly, they demonstrate a widespread involvement of EphB1 receptors in chronic pain. NR2B phosphorylation, c-fos expression and microglial activation are all reduced in EphB1 knockout mice. This last finding is intriguing, since microglial activation is supposedly triggered directly by primary afferents, therefore it was not expected to be affected. Interestingly, in some models of long-term pain (days, mechanical and thermal hyperalgesia develop both in wild type and EphB1 knockout mice, but recovery is faster in the latter, indicating that in particular models these receptors are required for the maintenance

  11. Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis).

    Science.gov (United States)

    Pajeva, Ilza K; Wiese, Michael

    2002-12-19

    A general pharmacophore model of P-glycoprotein (P-gp) drugs is proposed that is based on a highly diverse data set and relates to the verapamil binding site of the protein. It is derived from structurally different drugs using the program GASP. The pharmacophore model consists of two hydrophobic points, three hydrogen bond (HB) acceptor points, and one HB donor point. Pharmacophore patterns of various drugs are obtained, and different binding modes are presumed for some of them. It is concluded that the binding affinity of the drugs depends on the number of the pharmacophore points simultaneously involved in the interaction with P-gp. On the basis of the obtained results, a hypothesis is proposed to explain the broad structural variety of the P-gp substrates and inhibitors: (i) the verapamil binding site of P-gp has several points that can participate in hydrophobic and HB interactions; (ii) different drugs can interact with different receptor points in different binding modes.

  12. Semi-Implicit Algorithm for Elastoplastic Damage Models Involving Energy Integration

    Directory of Open Access Journals (Sweden)

    Ji Zhang

    2016-01-01

    Full Text Available This study aims to develop a semi-implicit constitutive integration algorithm for a class of elastoplastic damage models where calculation of damage energy release rates involves integration of free energy. The constitutive equations with energy integration are split into the elastic predictor, plastic corrector, and damage corrector. The plastic corrector is solved with an improved format of the semi-implicit spectral return mapping, which is characterized by constant flow direction and plastic moduli calculated at initial yield, enforcement of consistency at the end, and coordinate-independent formulation with an orthogonally similar stress tensor. The tangent stiffness consistent with the updating algorithm is derived. The algorithm is implemented with a recently proposed elastoplastic damage model for concrete, and several typical mechanical tests of reinforced concrete components are simulated. The present semi-implicit algorithm proves to achieve a balance between accuracy, stability, and efficiency compared with the implicit and explicit algorithms and calculate free energy accurately with small time steps.

  13. A structural model of customer satisfaction and trust in vendors involved in mobile commerce

    Directory of Open Access Journals (Sweden)

    Suki, N.M.

    2011-01-01

    Full Text Available The purpose of this paper is to provide an explanation of factors influencing customer satisfaction and trust in vendors involved in mobile commerce (m-commerce. The study sample consists of 200 respondents. Data were analyzed by employing structural equation modelling (SEM supported by AMOS 5.0 with maximum likelihood estimation in order to test the proposed hypotheses. The proposed model was empirically tested and results confirmed that users’ satisfaction with vendors in m-commerce was not significantly influenced by two antecedents of the vendor’s website quality: interactivity and customisation, and also two antecedents of mobile technology quality: usefulness and ease-of-use. Meanwhile, users’ trust towards the vendor in m-commerce is affected by users’ satisfaction with the vendor. Interestingly, vendor quality dimensions such as responsiveness and brand image influence customer satisfaction with vendors in m-commerce. Based on the findings, vendors in m-commerce should focus on the factors which generate more satisfaction and trust among customers. For vendors in general, the results can help them to better develop customer trust in m-commerce. Vendors of m-commerce can provide a more satisfying experience for customers.

  14. Involving mental health service users in suicide-related research: a qualitative inquiry model.

    Science.gov (United States)

    Lees, David; Procter, Nicholas; Fassett, Denise; Handley, Christine

    2016-03-01

    To describe the research model developed and successfully deployed as part of a multi-method qualitative study investigating suicidal service-users' experiences of mental health nursing care. Quality mental health care is essential to limiting the occurrence and burden of suicide, however there is a lack of relevant research informing practice in this context. Research utilising first-person accounts of suicidality is of particular importance to expanding the existing evidence base. However, conducting ethical research to support this imperative is challenging. The model discussed here illustrates specific and more generally applicable principles for qualitative research regarding sensitive topics and involving potentially vulnerable service-users. Researching into mental health service users with first-person experience of suicidality requires stakeholder and institutional support, researcher competency, and participant recruitment, consent, confidentiality, support and protection. Research with service users into their experiences of sensitive issues such as suicidality can result in rich and valuable data, and may also provide positive experiences of collaboration and inclusivity. If challenges are not met, objectification and marginalisation of service-users may be reinforced, and limitations in the evidence base and service provision may be perpetuated.

  15. An ODE for an overloaded X model involving a stochastic averaging principle

    Directory of Open Access Journals (Sweden)

    Ward Whitt

    2011-01-01

    Full Text Available We study an ordinary differential equation (ODE arising as the many-server heavy-traffic fluid limit of a sequence of overloaded Markovian queueing models with two customer classes and two service pools. The system, known as the X model in the call-center literature, operates under the fixed-queue-ratio-with-thresholds (FQR-T control, which we proposed in a recent paper as a way for one service system to help another in face of an unanticipated overload. Each pool serves only its own class until a threshold is exceeded; then one-way sharing is activated with all customer-server assignments then driving the two queues toward a fixed ratio. For large systems, that fixed ratio is achieved approximately. The ODE describes system performance during an overload. The control is driven by a queue-difference stochastic process, which operates in a faster time scale than the queueing processes themselves, thus achieving a time-dependent steady state instantaneously in the limit. As a result, for the ODE, the driving process is replaced by its long-run average behavior at each instant of time; i.e., the ODE involves a heavy-traffic averaging principle (AP.

  16. Yeast Mitochondrial Interactosome Model: Metabolon Membrane Proteins Complex Involved in the Channeling of ADP/ATP

    Directory of Open Access Journals (Sweden)

    Benjamin Clémençon

    2012-02-01

    Full Text Available The existence of a mitochondrial interactosome (MI has been currently well established in mammalian cells but the exact composition of this super-complex is not precisely known, and its organization seems to be different from that in yeast. One major difference is the absence of mitochondrial creatine kinase (MtCK in yeast, unlike that described in the organization model of MI, especially in cardiac, skeletal muscle and brain cells. The aim of this review is to provide a detailed description of different partner proteins involved in the synergistic ADP/ATP transport across the mitochondrial membranes in the yeast Saccharomyces cerevisiae and to propose a new mitochondrial interactosome model. The ADP/ATP (Aacp and inorganic phosphate (PiC carriers as well as the VDAC (or mitochondrial porin catalyze the import and export of ADP, ATP and Pi across the mitochondrial membranes. Aacp and PiC, which appear to be associated with the ATP synthase, consist of two nanomotors (F0, F1 under specific conditions and form ATP synthasome. Identification and characterization of such a complex were described for the first time by Pedersen and co-workers in 2003.

  17. Modeling economic costs of disasters and recovery involving positive effects of reconstruction: analysis using a dynamic CGE model

    Directory of Open Access Journals (Sweden)

    W. Xie

    2013-11-01

    Full Text Available Disaster damages have negative effects on economy, whereas reconstruction investments have positive effects. The aim of this study is to model economic causes of disasters and recovery involving positive effects of reconstruction activities. Computable general equilibrium (CGE model is a promising approach because it can incorporate these two kinds of shocks into a unified framework and further avoid double-counting problem. In order to factor both shocks in CGE model, direct loss is set as the amount of capital stock reduced on supply side of economy; A portion of investments restore the capital stock in existing period; An investment-driven dynamic model is formulated due to available reconstruction data, and the rest of a given country's saving is set as an endogenous variable. The 2008 Wenchuan Earthquake is selected as a case study to illustrate the model, and three scenarios are constructed: S0 (no disaster occurs, S1 (disaster occurs with reconstruction investment and S2 (disaster occurs without reconstruction investment. S0 is taken as business as usual, and the differences between S1 and S0 and that between S2 and S0 can be interpreted as economic losses including reconstruction and excluding reconstruction respectively. The study showed that output from S1 is found to be closer to real data than that from S2. S2 overestimates economic loss by roughly two times that under S1. The gap in economic aggregate between S1 and S0 is reduced to 3% in 2011, a level that should take another four years to achieve under S2.

  18. Involvement of Autophagic Pathway in the Progression of Retinal Degeneration in a Mouse Model of Diabetes.

    Science.gov (United States)

    Piano, Ilaria; Novelli, Elena; Della Santina, Luca; Strettoi, Enrica; Cervetto, Luigi; Gargini, Claudia

    2016-01-01

    The notion that diabetic retinopathy (DR) is essentially a micro-vascular disease has been recently challenged by studies reporting that vascular changes are preceded by signs of damage and loss of retinal neurons. As to the mode by which neuronal death occurs, the evidence that apoptosis is the main cause of neuronal loss is far from compelling. The objective of this study was to investigate these controversies in a mouse model of streptozotocin (STZ) induced diabetes. Starting from 8 weeks after diabetes induction there was loss of rod but not of cone photoreceptors, together with reduced thickness of the outer and inner synaptic layers. Correspondingly, rhodopsin expression was downregulated and the scotopic electroretinogram (ERG) is suppressed. In contrast, cone opsin expression and photopic ERG response were not affected. Suppression of the scotopic ERG preceded morphological changes as well as any detectable sign of vascular alteration. Only sparse apoptotic figures were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and glia was not activated. The physiological autophagy flow was altered instead, as seen by increased LC3 immunostaining at the level of outer plexiform layer (OPL) and upregulation of the autophagic proteins Beclin-1 and Atg5. Collectively, our results show that the streptozotocin induced DR in mouse initiates with a functional loss of the rod visual pathway. The pathogenic pathways leading to cell death develop with the initial dysregulation of autophagy well before the appearance of signs of vascular damage and without strong involvement of apoptosis.

  19. The Oskarshamn model for public involvement in the siting of nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    Aahagen, H. [Ahagen and Co (Sweden); CarIsson, Torsten [Mayor, Oskarshamn (Sweden); Hallberg, K. [Local Competence Building, Oskarshamn (Sweden); Andersson, Kjell [Karinta-Konsult, Taeby(Sweden)

    1999-12-01

    The Oskarshamn model has so far worked extremely well as a tool to achieve openness and public participation. The municipality involvement has been successful in several aspects, e.g.: It has been possible to influence the program, to a large extent, to meet certain municipality conditions and to ensure the local perspective. The local competence has increased to a considerable degree. The activities generated by the six working groups with a total of 40 members have generated a large number of contacts with various organisations, schools, mass media, individuals in the general public and interest groups. For the future, clarification of the disposal method and site selection criteria as well as the site selection process as such is crucial. The municipality has also emphasised the importance of SKB having shown the integration between site selection criteria, the feasibility study and the safety assessment. Furthermore, the programs for the encapsulation facility and the repository must be co-ordinated. For Oskarshamn it will be of utmost importance that the repository is well under way to be realised before the encapsulation facility can be built.

  20. Association of father involvement and neighborhood quality with kindergartners' physical activity: a multilevel structural equation model.

    Science.gov (United States)

    Beets, Michael W; Foley, John T

    2008-01-01

    Examine the effects of father-child involvement and neighborhood characteristics with young children's physical activity (PA) within a multilevel framework. Cross-sectional analysis of the Early Childhood Longitudinal Study-Kindergarten Cohort 1998. Nationally representative sample. Data were available for 10,694 kindergartners (5-6 years; 5240 girls) living in 1053 neighborhoods. Parental report of child's PA level, father characteristics (e.g., time spent with child, age, education, socioeconomic status, hours worked), family time spent doing sports/ activities together, and neighborhood quality (e.g., safety, presence of crime violence, garbage). Child weight status, motor skills, ethnicity, and television viewing were used as covariates. Multilevel structural equation modeling with children nested within neighborhoods. At the child level father-child time and family time doing sports together were positively associated with children's PA. At the neighborhood level parental perception of a neighborhood's safety for children to play outside fully mediated the effect of neighborhood quality on children's PA. Overall 19.1% and 7.6% of the variance in PA was explained at the child and neighborhood levels, respectively. Family-based interventions for PA should consider father-child time, with this contributing to a child's overall PA level. Further, neighborhood quality is an important predictor of PA only to the extent by which parents perceive it to be unsafe for their child to play outdoors.

  1. Characterization of Pneumococcal Genes Involved in Bloodstream Invasion in a Mouse Model.

    Directory of Open Access Journals (Sweden)

    Layla K Mahdi

    Full Text Available Streptococcus pneumoniae (the pneumococcus continues to account for significant morbidity and mortality worldwide, causing life-threatening diseases such as pneumonia, bacteremia and meningitis, as well as less serious infections such as sinusitis, conjunctivitis and otitis media. Current polysaccharide vaccines are strictly serotype-specific and also drive the emergence of non-vaccine serotype strains. In this study, we used microarray analysis to compare gene expression patterns of either serotype 4 or serotype 6A pneumococci in the nasopharynx and blood of mice, as a model to identify genes involved in invasion of blood in the context of occult bacteremia in humans. In this manner, we identified 26 genes that were significantly up-regulated in the nasopharynx and 36 genes that were significantly up-regulated in the blood that were common to both strains. Gene Ontology classification revealed that transporter and DNA binding (transcription factor activities constitute the significantly different molecular functional categories for genes up-regulated in the nasopharynx and blood. Targeted mutagenesis of selected genes from both niches and subsequent virulence and pathogenesis studies identified the manganese-dependent superoxide dismutase (SodA as most likely to be essential for colonization, and the cell wall-associated serine protease (PrtA as important for invasion of blood. This work extends our previous analyses and suggests that both PrtA and SodA warrant examination in future studies aimed at prevention and/or control of pneumococcal disease.

  2. Harnessing and supporting consumer involvement in the development and implementation of Models of Care for musculoskeletal health.

    Science.gov (United States)

    Walsh, Louisa; Hill, Sophie; Wluka, Anita E; Brooks, Peter; Buchbinder, Rachelle; Cahill, Ainslie; Dans, Leonila F; Lowe, Dianne; Taylor, Michael; Tugwell, Peter

    2016-06-01

    Consumer involvement in the design and delivery of their healthcare is an integral strategy to ensure that health services and systems meet consumers' needs. This is also true for the design and delivery of Models of Care. This chapter presents the identified healthcare needs of people with musculoskeletal conditions and focuses on the current systematic review evidence for consumer involvement interventions in musculoskeletal Models of Care across the micro, meso and macro levels of healthcare. This chapter also presents three case studies of consumer involvement in different aspects of healthcare, offers a series of practice points to help translate the systematic review evidence into practice, and also provides direction to available resources, which support the implementation of consumer involvement within Models of Care.

  3. Modelling skin surface areas involved in water transfer in the Palmate Newt (Lissotriton helveticus)

    National Research Council Canada - National Science Library

    Wardziak, Thomas; Oxarango, Laurent; Valette, Sebastien; Mahieu-Williame, Laurent; Joly, Pierre

    2014-01-01

    Magnetic resonance imaging (MRI) based 3D reconstructions were used to derive accurate quantitative data on body volume and functional skin surface areas involved in water transfer in the Palmate Newt...

  4. Analysis and Modeling of Pedestrian Walking Behaviors Involving Individuals with Disabilities

    OpenAIRE

    Sharifi, Mohammad Sadra

    2016-01-01

    The objective of this dissertation was to study walking behaviors of pedestrian groups involving individuals with disabilities. To this end, large scale controlled walking experiments were conducted at Utah State University (USU) to examine walking behaviors in various walking facility types, such as passageway, right angle, oblique angle, queuing area, bottleneck, and stairs. Walking experiments were conducted over four days involving participants with and without disabilities. Automated vid...

  5. TLR4 is involved in the pathogenic effects observed in a murine model of antiphospholipid syndrome.

    Science.gov (United States)

    Xie, Hongxiang; Kong, Xiangmin; Zhou, Hong; Xie, Yachao; Sheng, Liangju; Wang, Ting; Xia, Longfei; Yan, Jinchuan

    2015-10-01

    Antiphospholipid (aPL)/anti-β2-glycoprotein I (β2GPI) antibodies are considered to play a pivotal pathogenic role in antiphospholipid syndrome (APS) by inducing an intracellular signaling and procoagulant/proinflammatory phenotype that leads to thrombosis. There is increasing evidence that Toll-like receptor 4 (TLR4) could serve as an important molecule for anti-β2GPI recognition on target cells. However, few studies have focused on the effects of TLR4 in in vivo models. Here, we investigated the role of TLR4 in the pathogenic effects of aPL/anti-β2GPI more precisely using TLR4-intact (C3H/HeN) and TLR4-defective (C3H/HeJ) mice. C3H/HeN and C3H/HeJ mice were injected with either IgG isolated from patient with APS (IgG-APS) or epitope-specific anti-β2GPI purified from β2GPI peptide-immunized rabbits. We found that, following anti-β2GPI injections and vascular injury, thrombus formation in both the carotid artery and femoral vein was markedly reduced in C3H/HeJ mice when compared with C3H/HeN mice. IgG-APS or anti-β2GPI-induced carotid artery and peritoneal macrophage tissue factor activity/expression was significantly lesser in C3H/HeJ than in C3H/HeN mice. Furthermore, the IgG-APS or anti-β2GPI induced expression of VCAM-1, ICAM-1, and E-selectin in the aorta and of IL-1β, IL-6, and TNF-α in peritoneal macrophages of C3H/HeJ mice was also significantly reduced compared to C3H/HeN mice. Together, these data suggest that TLR4 is involved in the pathogenic effects of aPL/anti-β2GPI antibodies in vivo.

  6. Development and Validation of a Needs Assessment Model Using Stakeholders Involved in a University Program.

    Science.gov (United States)

    Labrecque, Monique

    1999-01-01

    Developed a needs-assessment model and validated the model with five groups of stakeholders connected with an undergraduate university nursing program in Canada. Used focus groups, questionnaires, a hermeneutic approach, and the magnitude-estimation scaling model to validate the model. Results show that respondents must define need to clarify the…

  7. Compatibility in the Biomphalaria glabrata/Echinostoma caproni model: potential involvement of adhesion genes.

    Science.gov (United States)

    Bouchut, A; Roger, E; Coustau, C; Gourbal, B; Mitta, G

    2006-02-01

    Because susceptibility or resistance of Biomphalaria glabrata to the trematode Echinostoma caproni correlates with differential hemocytic adhesive properties, we compared the expression of genes involved in adhesion processes between hemocytes from susceptible and resistant snails. Quantitative reverse transcriptase-PCR analysis revealed four genes whose transcripts were differentially represented between hemocytes from resistant and susceptible snails. These genes encode two dermatopontin-like, one matrilin-like and one cadherin-like proteins. Expression analyses performed following parasite exposure suggested that dermatopontins may be involved in the compatibility differences between these strains. We also investigated expression levels on whole snails of different genes potentially involved in extracellular matrix structure or coagulation. Our results support the hypothesis that susceptible snails possess a hemolymph coagulation-like system that is more potent than that of resistant snails. This system may prevent hemocyte migration towards the parasite larvae and therefore facilitate parasite settlement in susceptible snails.

  8. VARIABLE SELECTION BY PSEUDO WAVELETS IN HETEROSCEDASTIC REGRESSION MODELS INVOLVING TIME SERIES

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A simple but efficient method has been proposed to select variables in heteroscedastic regression models. It is shown that the pseudo empirical wavelet coefficients corresponding to the significant explanatory variables in the regression models are clearly larger than those nonsignificant ones, on the basis of which a procedure is developed to select variables in regression models. The coefficients of the models are also estimated. All estimators are proved to be consistent.

  9. Psychometric Framework for Modeling Parental Involvement and Reading Literacy. IEA Research for Education

    Science.gov (United States)

    Punter, R. Annemiek; Glas, Cees A. W.; Meelissen, Martina R. M.

    2016-01-01

    Parental involvement is seen as one of the most malleable factors of the student's home situation, which makes it a relevant subject for schools, educational policies, and research. Though many studies have researched its role in student achievement, effects are not univocal. It is difficult to tell whether these inconsistent results are caused by…

  10. The Impact of Field Trips and Family Involvement on Mental Models of the Desert Environment

    Science.gov (United States)

    Judson, Eugene

    2011-07-01

    This study examined the mental models of the desert environment held by fourth- and seventh-grade students in the USA and whether those mental models could be affected by: (1) classroom field trips to a desert riparian preserve, and (2) interaction with family members at the same preserve. Results generally indicated that students in this study were resolute in their models and that field trips did not impact the types of models students adhered to. Twenty-three seventh-grade students who self-selected to participate in a Family Science Club with their parents did demonstrate a shift in their mental models and developed significantly more sophisticated models over time. A critical implication of the study is that unless transformation of mental models of the environment is an explicit goal of instruction, simple exposure to the environment (even within the context of life science instruction) will not transform understandings of how organisms within an environment act and interact interdependently.

  11. A Framework for Quantitative Modeling of Neural Circuits Involved in Sleep-to-Wake Transition

    Directory of Open Access Journals (Sweden)

    Siamak eSorooshyari

    2015-02-01

    Full Text Available Identifying the neuronal circuits and dynamics of sleep-to-wake transition is essential to understanding brain regulation of behavioral states, including sleep-wake cycles, arousal, and hyperarousal. Recent work by different laboratories has used optogenetics to determine the role of individual neuromodulators in state transitions. The optogenetically-driven data does not yet provide a multi-dimensional schematic of the mechanisms underlying changes in vigilance states. This work presents a modeling framework to interpret, assist, and drive research on the sleep-regulatory network. We identify feedback, redundancy, and gating hierarchy as three fundamental aspects of this model. The presented model is expected to expand as additional data on the contribution of each transmitter to a vigilance state becomes available. Incorporation of conductance-based models of neuronal ensembles into this model and existing models of cortical excitability will provide more comprehensive insight into sleep dynamics as well as sleep and arousal-related disorders.

  12. A Framework for Quantitative Modeling of Neural Circuits Involved in Sleep-to-Wake Transition

    Science.gov (United States)

    Sorooshyari, Siamak; Huerta, Ramón; de Lecea, Luis

    2015-01-01

    Identifying the neuronal circuits and dynamics of sleep-to-wake transition is essential to understanding brain regulation of behavioral states, including sleep–wake cycles, arousal, and hyperarousal. Recent work by different laboratories has used optogenetics to determine the role of individual neuromodulators in state transitions. The optogenetically driven data do not yet provide a multi-dimensional schematic of the mechanisms underlying changes in vigilance states. This work presents a modeling framework to interpret, assist, and drive research on the sleep-regulatory network. We identify feedback, redundancy, and gating hierarchy as three fundamental aspects of this model. The presented model is expected to expand as additional data on the contribution of each transmitter to a vigilance state becomes available. Incorporation of conductance-based models of neuronal ensembles into this model and existing models of cortical excitability will provide more comprehensive insight into sleep dynamics as well as sleep and arousal-related disorders. PMID:25767461

  13. Unique Solution of a Coupled Fractional Differential System Involving Integral Boundary Conditions from Economic Model

    Directory of Open Access Journals (Sweden)

    Rui Li

    2013-01-01

    Full Text Available We study the existence and uniqueness of the positive solution for the fractional differential system involving the Riemann-Stieltjes integral boundary conditions , , , , , and , where , , and and are the standard Riemann-Liouville derivatives, and are functions of bounded variation, and and denote the Riemann-Stieltjes integral. Our results are based on a generalized fixed point theorem for weakly contractive mappings in partially ordered sets.

  14. Modeling and Parameter Identification Involving 3-Hydroxypropionaldehyde Inhibitory Effects in Glycerol Continuous Fermentation

    Directory of Open Access Journals (Sweden)

    Zhaohua Gong

    2012-01-01

    Full Text Available Mathematical modeling and parameter estimation are critical steps in the optimization of biotechnological processes. In the 1,3-propanediol (1,3-PD production by glycerol fermentation process under anaerobic conditions, 3-hydroxypropionaldehyde (3-HPA accumulation would arouse an irreversible cessation of the fermentation process. Considering 3-HPA inhibitions to cells growth and to activities of enzymes, we propose a novel mathematical model to describe glycerol continuous cultures. Some properties of the above model are discussed. On the basis of the concentrations of extracellular substances, a parameter identification model is established to determine the kinetic parameters in the presented system. Through the penalty function technique combined with an extension of the state space method, an improved genetic algorithm is then constructed to solve the parameter identification model. An illustrative numerical example shows the appropriateness of the proposed model and the validity of optimization algorithm. Since it is difficult to measure the concentrations of intracellular substances, a quantitative robustness analysis method is given to infer whether the model is plausible for the intracellular substances. Numerical results show that the proposed model is of good robustness.

  15. Increasing Parental Involvement in the Primary Grades: The Magowan School Model.

    Science.gov (United States)

    Galen, Harlene

    Each school's version of a partnership with parents is unique, and no generic model exists. Designated in 1988 as one of 14 model schools in the New Jersey State Department of Education "Parents as Partners in Learning" project, the Mildred Magowan school in Edgewater Park has followed a systematic approach that has consistently led to…

  16. A Computational Model of a Descending Mechanosensory Pathway Involved in Active Tactile Sensing.

    Directory of Open Access Journals (Sweden)

    Jan M Ache

    2015-07-01

    Full Text Available Many animals, including humans, rely on active tactile sensing to explore the environment and negotiate obstacles, especially in the dark. Here, we model a descending neural pathway that mediates short-latency proprioceptive information from a tactile sensor on the head to thoracic neural networks. We studied the nocturnal stick insect Carausius morosus, a model organism for the study of adaptive locomotion, including tactually mediated reaching movements. Like mammals, insects need to move their tactile sensors for probing the environment. Cues about sensor position and motion are therefore crucial for the spatial localization of tactile contacts and the coordination of fast, adaptive motor responses. Our model explains how proprioceptive information about motion and position of the antennae, the main tactile sensors in insects, can be encoded by a single type of mechanosensory afferents. Moreover, it explains how this information is integrated and mediated to thoracic neural networks by a diverse population of descending interneurons (DINs. First, we quantified responses of a DIN population to changes in antennal position, motion and direction of movement. Using principal component (PC analysis, we find that only two PCs account for a large fraction of the variance in the DIN response properties. We call the two-dimensional space spanned by these PCs 'coding-space' because it captures essential features of the entire DIN population. Second, we model the mechanoreceptive input elements of this descending pathway, a population of proprioceptive mechanosensory hairs monitoring deflection of the antennal joints. Finally, we propose a computational framework that can model the response properties of all important DIN types, using the hair field model as its only input. This DIN model is validated by comparison of tuning characteristics, and by mapping the modelled neurons into the two-dimensional coding-space of the real DIN population. This

  17. A Computational Model of a Descending Mechanosensory Pathway Involved in Active Tactile Sensing.

    Science.gov (United States)

    Ache, Jan M; Dürr, Volker

    2015-07-01

    Many animals, including humans, rely on active tactile sensing to explore the environment and negotiate obstacles, especially in the dark. Here, we model a descending neural pathway that mediates short-latency proprioceptive information from a tactile sensor on the head to thoracic neural networks. We studied the nocturnal stick insect Carausius morosus, a model organism for the study of adaptive locomotion, including tactually mediated reaching movements. Like mammals, insects need to move their tactile sensors for probing the environment. Cues about sensor position and motion are therefore crucial for the spatial localization of tactile contacts and the coordination of fast, adaptive motor responses. Our model explains how proprioceptive information about motion and position of the antennae, the main tactile sensors in insects, can be encoded by a single type of mechanosensory afferents. Moreover, it explains how this information is integrated and mediated to thoracic neural networks by a diverse population of descending interneurons (DINs). First, we quantified responses of a DIN population to changes in antennal position, motion and direction of movement. Using principal component (PC) analysis, we find that only two PCs account for a large fraction of the variance in the DIN response properties. We call the two-dimensional space spanned by these PCs 'coding-space' because it captures essential features of the entire DIN population. Second, we model the mechanoreceptive input elements of this descending pathway, a population of proprioceptive mechanosensory hairs monitoring deflection of the antennal joints. Finally, we propose a computational framework that can model the response properties of all important DIN types, using the hair field model as its only input. This DIN model is validated by comparison of tuning characteristics, and by mapping the modelled neurons into the two-dimensional coding-space of the real DIN population. This reveals the versatility

  18. Competitive growth model involving random deposition and random deposition with surface relaxation

    Energy Technology Data Exchange (ETDEWEB)

    Horowitz, Claudio M.; Monetti, Roberto A.; Albano, Ezequiel V.

    2001-06-01

    A deposition model that considers a mixture of random deposition with surface relaxation and a pure random deposition is proposed and studied. As the system evolves, random deposition with surface relaxation (pure random deposition) take place with probability p and (1{minus}p), respectively. The discrete (microscopic) approach to the model is studied by means of extensive numerical simulations, while continuous equations are used in order to investigate the mesoscopic properties of the model. A dynamic scaling ansatz for the interface width W(L,t,p) as a function of the lattice side L, the time t and p is formulated and tested. Three exponents, which can be linked to the standard growth exponent of random deposition with surface relaxation by means of a scaling relation, are identified. In the continuous limit, the model can be well described by means of a phenomenological stochastic growth equation with a p-dependent effective surface tension.

  19. Deformation analysis of polymers composites: rheological model involving time-based fractional derivative

    DEFF Research Database (Denmark)

    Zhou, H. W.; Yi, H. Y.; Mishnaevsky, Leon

    2016-01-01

    A modeling approach to time-dependent property of Glass Fiber Reinforced Polymers (GFRP) composites is of special interest for quantitative description of long-term behavior. An electronic creep machine is employed to investigate the time-dependent deformation of four specimens of dog......-bond-shaped GFRP composites at various stress level. A negative exponent function based on structural changes is introduced to describe the damage evolution of material properties in the process of creep test. Accordingly, a new creep constitutive equation, referred to fractional derivative Maxwell model...... by the fractional derivative Maxwell model proposed in the paper are in a good agreement with the experimental data. It is shown that the new creep constitutive model proposed in the paper needs few parameters to represent various time-dependent behaviors....

  20. A model of a fishery with fish stock involving delay equations.

    Science.gov (United States)

    Auger, P; Ducrot, Arnaud

    2009-12-13

    The aim of this paper is to provide a new mathematical model for a fishery by including a stock variable for the resource. This model takes the form of an infinite delay differential equation. It is mathematically studied and a bifurcation analysis of the steady states is fulfilled. Depending on the different parameters of the problem, we show that Hopf bifurcation may occur leading to oscillating behaviours of the system. The mathematical results are finally discussed.

  1. Deformation analysis of polymers composites: rheological model involving time-based fractional derivative

    Science.gov (United States)

    Zhou, H. W.; Yi, H. Y.; Mishnaevsky, L.; Wang, R.; Duan, Z. Q.; Chen, Q.

    2016-08-01

    A modeling approach to time-dependent property of Glass Fiber Reinforced Polymers (GFRP) composites is of special interest for quantitative description of long-term behavior. An electronic creep machine is employed to investigate the time-dependent deformation of four specimens of dog-bond-shaped GFRP composites at various stress level. A negative exponent function based on structural changes is introduced to describe the damage evolution of material properties in the process of creep test. Accordingly, a new creep constitutive equation, referred to fractional derivative Maxwell model, is suggested to characterize the time-dependent behavior of GFRP composites by replacing Newtonian dashpot with the Abel dashpot in the classical Maxwell model. The analytic solution for the fractional derivative Maxwell model is given and the relative parameters are determined. The results estimated by the fractional derivative Maxwell model proposed in the paper are in a good agreement with the experimental data. It is shown that the new creep constitutive model proposed in the paper needs few parameters to represent various time-dependent behaviors.

  2. Involvement of upregulation of miR-210 in a rat epilepsy model

    Science.gov (United States)

    Chen, Licheng; Zheng, Hao; Zhang, Shimeng

    2016-01-01

    Epilepsy is a common type of neurological disorder with complex etiology. The mechanisms are still not clear. MicroRNAs are endogenous noncoding RNAs with many physiological activities. Multiple microRNAs were abnormally expressed in status epilepticus, including miR-210. In this study, we applied lithium chloride and pilocarpine to induce epileptic activity and aimed to disclose the potential mechanisms. Our data showed that miR-210 was significantly upregulated in hippocampus one day after modeling (P<0.05 vs control) and the high expression of miR-210 lasted for at least 30 days. By contrast, γ-aminobutyric acid (GABA) level significantly decreased concurrently after modeling (P<0.05 vs control). To question whether miR-210 could be a potential therapeutic target for epilepsy, miR-210 inhibitor was administrated through intrahippocampal injection after epilepsy modeling. Our data showed that morphological changes of hippocampal neurons and apoptosis triggered by epilepsy were mitigated by miR-210 inhibition. More importantly, the expressions of GABA-related proteins, including GABAA receptor α1, glutamate decarboxylase, and GABA transporter 1, were significantly elevated after epilepsy modeling in both mRNA and protein levels 3 days postmodeling (P<0.05 vs control), which were mitigated by miR-210 inhibitor treatment (P<0.05 vs model). In addition, epilepsy-induced upregulation of GABA transaminase was alleviated by miR-210 inhibitor. Taken together, these data implicated potential roles of miR-210 in lithium chloride–pilocarpine-induced epilepsy model and miR-210 could serve as a potential therapeutic target in status epilepticus. PMID:27471387

  3. Two Scales, Hybrid Model for Soils, Involving Artificial Neural Network and Finite Element Procedure

    Directory of Open Access Journals (Sweden)

    Krasiński Marcin

    2015-02-01

    Full Text Available A hybrid ANN-FE solution is presented as a result of two level analysis of soils: a level of a laboratory sample and a level of engineering geotechnical problem. Engineering properties of soils (sands are represented directly in the form of ANN (this is in contrast with our former paper where ANN approximated constitutive relationships. Initially the ANN is trained with Duncan formula (Duncan and Chang [2], then it is re-trained (calibrated with some available experimental data, specific for the soil considered. The obtained approximation of the constitutive parameters is used directly in finite element method at the level of a single element at the scale of the laboratory sample to check the correct representation of the laboratory test. Then, the finite element that was successfully tested at the level of laboratory sample is used at the macro level to solve engineering problems involving the soil for which it was calibrated.

  4. An ODE for an Overloaded X Model Involving a Stochastic Averaging Principle

    OpenAIRE

    Ward Whitt; Ohad Perry

    2010-01-01

    We study an ordinary differential equation (ODE) arising as the many-server heavy-traffic fluid limit of a sequence of overloaded Markovian queueing models with two customer classes and two service pools. The system, known as the X model in the call-center literature, operates under the fixed-queue-ratio-with-thresholds (FQR-T) control, which we proposed in a recent paper as a way for one service system to help another in face of an unanticipated overload. Each pool serves only its own class ...

  5. Ethnic differences in the effect of parenting on gang involvement and gang delinquency: a longitudinal, hierarchical linear modeling perspective.

    Science.gov (United States)

    Walker-Barnes, C J; Mason, C A

    2001-01-01

    This study examined the relative influence of peer and parenting behavior on changes in adolescent gang involvement and gang-related delinquency. An ethnically diverse sample of 300 ninth-grade students was recruited and assessed on eight occasions during the school year. Analyses were conducted using hierarchical linear modeling. Results indicated that, in general, adolescents decreased their level of gang involvement over the course of the school year, whereas the average level of gang delinquency remained constant over time. As predicted, adolescent gang involvement and gang-related delinquency were most strongly predicted by peer gang involvement and peer gang delinquency, respectively. Nevertheless, parenting behavior continued to significantly predict change in both gang involvement and gang delinquency, even after controlling for peer behavior. A significant interaction between parenting and ethnic and cultural heritage found the effect of parenting to be particularly salient for Black students, for whom higher levels of behavioral control and lower levels of lax parental control were related to better behavioral outcomes over time, whereas higher levels of psychological control predicted worse behavioral outcomes.

  6. Data, analysis and modeling of physical properties for process designof systems involving lipids

    DEFF Research Database (Denmark)

    Cunico, Larissa; Ceriani, Roberta; Sarup, Bent

    2013-01-01

    Pure component and mixture properties are necessary for synthesis, design, and analysis of processes forthe production of edible oils, fats, biodiesel, and other lipids. The lack of measured data for these systemsmakes it necessary to develop reliable predictive models based on limited data. We...

  7. Model studies of volatile diesel exhaust particle formation: organic vapours involved in nucleation and growth?

    Science.gov (United States)

    Pirjola, L.; Karl, M.; Rönkkö, T.; Arnold, F.

    2015-02-01

    High concentration of volatile nucleation mode particles (NUP) formed in the atmosphere during exhaust cools and dilutes have hazardous health effects and impair visibility in urban areas. Nucleation mechanisms in diesel exhaust are only poorly understood. We performed model studies using two sectional aerosol dynamics process models AEROFOR and MAFOR on the formation of particles in the exhaust of a diesel engine, equipped with an oxidative after-treatment system and running with low fuel sulphur content (FSC), under laboratory sampling conditions where the dilution system mimics real-world conditions. Different nucleation mechanisms were tested; based on the measured gaseous sulphuric acid (GSA) and non-volatile core and soot particle number concentrations of the raw exhaust, the model simulations showed that the best agreement between model predictions and measurements in terms of particle number size distribution was obtained by barrierless heteromolecular homogeneous nucleation between GSA and semi-volatile organic vapour (for example adipic acid) combined with the homogeneous nucleation of GSA alone. Major growth of the particles was predicted to occur by the same organic vapour at concentrations of (1-2) ×1012cm-3. The pre-existing core and soot mode concentrations had opposite trend on the NUP formation, and maximum NUP formation was predicted if a diesel particle filter (DPF) was used. On the other hand, NUP formation was ceased if the GSA concentration was less than 1010cm-3 which suggests, based on the measurements, the usage of biofuel to prevent volatile particles in diesel exhaust.

  8. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models

    Science.gov (United States)

    Liu, Huiping; Patel, Manishkumar R.; Prescher, Jennifer A.; Patsialou, Antonia; Qian, Dalong; Lin, Jiahui; Wen, Susanna; Chang, Ya-Fang; Bachmann, Michael H.; Shimono, Yohei; Dalerba, Piero; Adorno, Maddalena; Lobo, Neethan; Bueno, Janet; Dirbas, Frederick M.; Goswami, Sumanta; Somlo, George; Condeelis, John; Contag, Christopher H.; Gambhir, Sanjiv Sam; Clarke, Michael F.

    2010-01-01

    To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44+ cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy. PMID:20921380

  9. The "Commitment Model" for Clinical Ethics Consultations: Society's Involvement in the Solution of Individual Cases.

    Science.gov (United States)

    Fournier, Véronique; Spranzi, Marta; Foureur, Nicolas; Brunet, Laurence

    2015-01-01

    Several approaches to clinical ethics consultation (CEC) exist in medical practice and are widely discussed in the clinical ethics literature; different models of CECs are classified according to their methods, goals, and consultant's attitude. Although the "facilitation" model has been endorsed by the American Society for Bioethics and Humanities (ASBH) and is described in an influential manual, alternative approaches, such as advocacy, moral expertise, mediation, and engagement are practiced and defended in the clinical ethics field. Our Clinical Ethics Center in Paris was founded in 2002 in the wake of the Patients' Rights Act, and to date it is the largest center that provides consultation services in France. In this article we shall describe and defend our own approach to clinical ethics consultation, which we call the "Commitment Model," in comparison with other existing models. Indeed commitment implies, among other meanings, continuity through time, a series of coherent actions, and the realization of important social goals. By drawing on a recent consultation case, we shall describe the main steps of our consultation procedure: interviews with major stakeholders, including patients and proxies; case conferences; and follow up. We shall show why we have chosen the term "commitment" to represent our approach at three different but interrelated levels: commitment towards patients, within the case conference group, and towards society as a whole.

  10. Submodels of model of nonlinear diffusion in the inhomogeneous medium involving absorption

    Energy Technology Data Exchange (ETDEWEB)

    Chirkunov, Yu. A., E-mail: chr101@mail.ru [Novosibirsk State Technical University, Marks Avenue 20, Novosibirsk 630073 (Russian Federation)

    2015-10-15

    We study the five-parameter model, describing the process of nonlinear diffusion in an inhomogeneous medium in the presence of absorption, for which the differential equation of the model admits a continuous Lie group of transformations, acting on the set of its solutions. We found six submodels of the original model of nonlinear diffusion, with different symmetry properties. Of these six submodels, the five submodels with transient absorption, for which the absorption coefficient depends on time according to a power law, represent the greatest interest with a mathematical point of view and with the point of view of physical applications. For each of these nonlinear submodels, we obtained formulas for producing new solutions that contain arbitrary constants, and we found all invariant submodels. All essentially distinct invariant solutions describing these invariant submodels are found in an explicit form or are reduced to finding the solution of nonlinear integral equations. The presence of the arbitrary constants in the integral equations that determine these solutions provide new opportunities for analytical and numerical study of boundary value problems for the received submodels and, thus, for the original model of nonlinear diffusion. For the received invariant submodels, we studied diffusion processes for which at the initial moment of the time at a fixed point is specified as a concentration and its gradient or as a concentration and its velocity. Solving of boundary value problems describing these processes is reduced to the solving of nonlinear integral equations. We established the existence and uniqueness of solutions of these boundary value problems under some additional conditions. The obtained results can be used to study the diffusion of substances, diffusion of conduction electrons and other particles, diffusion of physical fields and propagation of heat in inhomogeneous medium, and also to study a turbulence (Leith model, differential

  11. Model studies of volatile diesel exhaust particle formation: are organic vapours involved in nucleation and growth?

    Science.gov (United States)

    Pirjola, L.; Karl, M.; Rönkkö, T.; Arnold, F.

    2015-09-01

    A high concentration of volatile nucleation mode particles (NUP) formed in the atmosphere when the exhaust cools and dilutes has hazardous health effects and it impairs the visibility in urban areas. Nucleation mechanisms in diesel exhaust are only poorly understood. We performed model studies using two sectional aerosol dynamics process models AEROFOR and MAFOR on the formation of particles in the exhaust of a diesel engine, equipped with an oxidative after-treatment system and running with low fuel sulfur content (FSC) fuel, under laboratory sampling conditions where the dilution system mimics real-world conditions. Different nucleation mechanisms were tested. Based on the measured gaseous sulfuric acid (GSA) and non-volatile core and soot particle number concentrations of the raw exhaust, the model simulations showed that the best agreement between model predictions and measurements in terms of particle number size distribution was obtained by barrier-free heteromolecular homogeneous nucleation between the GSA and a semi-volatile organic vapour combined with the homogeneous nucleation of GSA alone. Major growth of the particles was predicted to occur due to the similar organic vapour at concentrations of (1-2) × 1012 cm-3. The pre-existing core and soot mode concentrations had an opposite trend on the NUP formation, and the maximum NUP formation was predicted if a diesel particle filter (DPF) was used. On the other hand, the model predicted that the NUP formation ceased if the GSA concentration in the raw exhaust was less than 1010 cm-3, which was the case when biofuel was used.

  12. Modelization of nanospace interaction involving a ferromagnetic atom: a spin polarization effect study by thermogravimetric analysis.

    Science.gov (United States)

    Santhanam, K S V; Chen, Xu; Gupta, S

    2014-04-01

    Ab initio studies of ferromagnetic atom interacting with carbon nanotubes have been reported in the literature that predict when the interaction is strong, a higher hybridization with confinement effect will result in spin polarization in the ferromagnetic atom. The spin polarization effect on the thermal oxidation to form its oxide is modeled here for the ferromagnetic atom and its alloy, as the above studies predict the 4s electrons are polarized in the atom. The four models developed here provide a pathway for distinguishing the type of interaction that exists in the real system. The extent of spin polarization in the ferromagnetic atom has been examined by varying the amount of carbon nanotubes in the composites in the thermogravimetric experiments. In this study we report the experimental results on the CoNi alloy which appears to show selective spin polarization. The products of the thermal oxidation has been analyzed by Fourier Transform Infrared Spectroscopy.

  13. Analysis of a Periodic Single Species Population Model Involving Constant Impulsive Perturbation

    Directory of Open Access Journals (Sweden)

    Ronghua Tan

    2014-01-01

    Full Text Available This is a continuation of the work of Tan et al. (2012. In this paper a periodic single species model controlled by constant impulsive perturbation is investigated. The constant impulse is realized at fixed moments of time. With the help of the comparison theorem of impulsive differential equations and Lyapunov functions, sufficient conditions for the permanence and global attractivity are established, respectively. Also, by comparing the above results with corresponding known results of Tan et al. (2012 (i.e., the above model with linear impulsive perturbations, we find that the two different types of impulsive perturbations have influence on the above dynamics. Numerical simulations are presented to substantiate our analytical results.

  14. The Undergraduate ALFALFA Team: A Model for Involving Undergraduates in Large Astronomy Collaborations

    Science.gov (United States)

    Craig, David W.; Koopmann, Rebecca A.; Haynes, Martha P.; Undergraduate ALFALFA Team, ALFALFA Team

    2016-01-01

    The NSF-sponsored Undergraduate ALFALFA (Arecibo Legacy Fast ALFA) Team (UAT) has allowed faculty and students from a wide range of public and private colleges and especially those with small astronomy programs to learn how science is accomplished in a large collaboration while contributing to the scientific goals of a legacy radio astronomy survey. This effort has been made possible through the collaboration of the ALFALFA PIs and graduate students, Arecibo Observatory staff, and the faculty at 19 undergraduate-focussed institutions. In this talk, we will discuss how the UAT model works for the ALFALFA project and lessons learned from our efforts over the 8 years of grant funding. We will provide suggestions on how the model could be applied to other legacy projects, particularly in such areas as online collaboration and software usage by undergraduates. This work has been supported by NSF grants AST-0724918/0902211, AST-075267/0903394, AST-0725380, and AST-1211005.

  15. Involvement of the Intrarenal Renin-Angiotensin System in Experimental Models of Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Maki Urushihara

    2012-01-01

    Full Text Available The intrarenal renin-angiotensin system (RAS has several pathophysiologic functions not only in blood pressure regulation but also in the development of glomerulonephritis (GN. Angiotensin II (Ang II is the biologically active product of the RAS. Locally produced Ang II induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation, regulates the gene expression of bioactive substances, and activates multiple intracellular signaling pathways, leading to tissue damage. Activation of the Ang II type 1 (AT1 receptor pathway results in the production of proinflammatory mediators, cell proliferation, and extracellular matrix synthesis, which facilitates glomerular injury. Previous studies have shown that angiotensin-converting enzyme inhibitors and/or AT1 receptor blockers have beneficial effects in experimental GN models and humans with various types of GN, and that these effects are more significant than their suppressive effects on blood pressure. In this paper, we focus on intrarenal RAS activation in the pathophysiology of experimental models of GN.

  16. Inventory Model for Deteriorating Items Involving Fuzzy with Shortages and Exponential Demand

    Directory of Open Access Journals (Sweden)

    Sharmila Vijai Stanly

    2015-11-01

    Full Text Available This paper considers the fuzzy inventory model for deteriorating items for power demand under fully backlogged conditions. We define various factors which are affecting the inventory cost by using the shortage costs. An intention of this paper is to study the inventory modelling through fuzzy environment. Inventory parameters, such as holding cost, shortage cost, purchasing cost and deterioration cost are assumed to be the trapezoidal fuzzy numbers. In addition, an efficient algorithm is developed to determine the optimal policy, and the computational effort and time are small for the proposed algorithm. It is simple to implement, and our approach is illustrated through some numerical examples to demonstrate the application and the performance of the proposed methodology.

  17. Switching model with two habitats and a predator involving group defence

    CERN Document Server

    Khan, Qamar J A; Jaju, R P

    2015-01-01

    Switching model with one predator and two prey species is considered. The prey species have the ability of group defence. Therefore, the predator will be attracted towards that habitat where prey are less in number. The stability analysis is carried out for two equilibrium values. The theoretical results are compared with the numerical results for a set of values. The Hopf bifuracation analysis is done to support the stability results.

  18. A metabolic model for members of the genus Tetrasphaera involved in enhanced biological phosphorus removal.

    Science.gov (United States)

    Kristiansen, Rikke; Nguyen, Hien Thi Thu; Saunders, Aaron Marc; Nielsen, Jeppe Lund; Wimmer, Reinhard; Le, Vang Quy; McIlroy, Simon Jon; Petrovski, Steve; Seviour, Robert J; Calteau, Alexandra; Nielsen, Kåre Lehmann; Nielsen, Per Halkjær

    2013-03-01

    Members of the genus Tetrasphaera are considered to be putative polyphosphate accumulating organisms (PAOs) in enhanced biological phosphorus removal (EBPR) from wastewater. Although abundant in Danish full-scale wastewater EBPR plants, how similar their ecophysiology is to 'Candidatus Accumulibacter phosphatis' is unclear, although they may occupy different ecological niches in EBPR communities. The genomes of four Tetrasphaera isolates (T. australiensis, T. japonica, T. elongata and T. jenkinsii) were sequenced and annotated, and the data used to construct metabolic models. These models incorporate central aspects of carbon and phosphorus metabolism critical to understanding their behavior under the alternating anaerobic/aerobic conditions encountered in EBPR systems. Key features of these metabolic pathways were investigated in pure cultures, although poor growth limited their analyses to T. japonica and T. elongata. Based on the models, we propose that under anaerobic conditions the Tetrasphaera-related PAOs take up glucose and ferment this to succinate and other components. They also synthesize glycogen as a storage polymer, using energy generated from the degradation of stored polyphosphate and substrate fermentation. During the aerobic phase, the stored glycogen is catabolized to provide energy for growth and to replenish the intracellular polyphosphate reserves needed for subsequent anaerobic metabolism. They are also able to denitrify. This physiology is markedly different to that displayed by 'Candidatus Accumulibacter phosphatis', and reveals Tetrasphaera populations to be unusual and physiologically versatile PAOs carrying out denitrification, fermentation and polyphosphate accumulation.

  19. Collaborative modelling for active involvement of stakeholders in urban flood risk management

    Directory of Open Access Journals (Sweden)

    M. Evers

    2012-09-01

    Full Text Available This paper presents an approach to enhance the role of local stakeholders in dealing with urban floods. The concept is based on the DIANE-CM project (Decentralised Integrated Analysis and Enhancement of Awareness through Collaborative Modelling and Management of Flood Risk of the 2nd ERANET CRUE funding initiative. The main objective of the project was to develop and test an advanced methodology for enhancing the resilience of local communities to flooding. Through collaborative modelling, a social learning process was initiated that enhances the social capacity of the stakeholders due to the interaction process. The other aim of the project was to better understand how data from hazard and vulnerability analyses and improved maps, as well as from the near real-time flood prediction, can be used to initiate a public dialogue (i.e. collaborative mapping and planning activities in order to carry out more informed and shared decision-making processes and to enhance flood risk awareness. The concept of collaborative modelling was applied in two case studies: (1 the Cranbrook catchment in the UK, with focus on pluvial flooding; and (2 the Alster catchment in Germany, with focus on fluvial flooding. As a result of the interactive and social learning process, supported by sociotechnical instruments, an understanding of flood risk was developed amongst the stakeholders and alternatives for flood risk management for the respective case study area were jointly developed and ranked as a basis for further planning and management.

  20. Involvement of Nitric Oxide in a Rat Model of Carrageenin-Induced Pleurisy

    Directory of Open Access Journals (Sweden)

    Masahiro Iwata

    2010-01-01

    Full Text Available Some evidence indicates that nitric oxide (NO contributes to inflammation, while other evidence supports the opposite conclusion. To clarify the role of NO in inflammation, we studied carrageenin-induced pleurisy in rats treated with an NO donor (NOC-18, a substrate for NO formation (L-arginine, and/or an NO synthase inhibitor (S-(2-aminoethyl isothiourea or NG-nitro-L-arginine. We assessed inflammatory cell migration, nitrite/nitrate values, lipid peroxidation and pro-inflammatory mediators. NOC-18 and L-arginine reduced the migration of inflammatory cells and edema, lowered oxidative stress, and normalized antioxidant enzyme activities. NO synthase inhibitors increased the exudate formation and inflammatory cell number, contributed to oxidative stress, induced an oxidant/antioxidant imbalance by maintaining high O−2, and enhanced the production of pro-inflammatory mediators. L-arginine and NOC-18 reversed the proinflammatory effects of NO synthase inhibitors, perhaps by reducing the expression of adhesion molecules on endothelial cells. Thus, our results indicate that NO is involved in blunting—not enhancing—the inflammatory response.

  1. A Hybrid Artificial Reputation Model Involving Interaction Trust, Witness Information and the Trust Model to Calculate the Trust Value of Service Providers

    Directory of Open Access Journals (Sweden)

    Gurdeep Singh Ransi

    2014-02-01

    Full Text Available Agent interaction in a community, such as the online buyer-seller scenario, is often uncertain, as when an agent comes in contact with other agents they initially know nothing about each other. Currently, many reputation models are developed that help service consumers select better service providers. Reputation models also help agents to make a decision on who they should trust and transact with in the future. These reputation models are either built on interaction trust that involves direct experience as a source of information or they are built upon witness information also known as word-of-mouth that involves the reports provided by others. Neither the interaction trust nor the witness information models alone succeed in such uncertain interactions. In this paper we propose a hybrid reputation model involving both interaction trust and witness information to address the shortcomings of existing reputation models when taken separately. A sample simulation is built to setup buyer-seller services and uncertain interactions. Experiments reveal that the hybrid approach leads to better selection of trustworthy agents where consumers select more reputable service providers, eventually helping consumers obtain more gains. Furthermore, the trust model developed is used in calculating trust values of service providers.

  2. The intervention model for affective involvement and its effectiveness: Fostering affective involvement between persons who are congenitally deafblind and their communication partners

    NARCIS (Netherlands)

    Martens, M.A.W.

    2014-01-01

    Can one share emotions with someone who can’t hear and see well? This dissertation addresses the effectiveness of a training for professionals to foster affective involvement or the mutual sharing of emotions with people who are congenitally deafblind. People with congenital deafblindness are

  3. Service Innovation Involved by Employees and Customers:From Conceptual Model to an IT Service Case

    Institute of Scientific and Technical Information of China (English)

    LIU De-wen; LU Ruo-yu

    2006-01-01

    With the service industry and information technology developing, Service innovation occurs continually in business today. It is important for service firms to understand the service's business and process;customer knowledge including needs, expectations and experiences.However, employees are key factor to collect the customer's advice. At the same time, employees may organize customers for the new service. So, the integration of employees and customers will help service firm in the way of developing a new service and upgrading a service. The paper describes some models to explain the relation based on some literatures and give some advices for service firms. At last, we introduce an IT service case

  4. Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development

    Directory of Open Access Journals (Sweden)

    R Pignatello

    2011-01-01

    Full Text Available Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physiological or pathological conditions, is important to exploit the molecular basis of many diseases and to identify new potential therapeutic strategies. Of course, the complexity of the structure and functions of biological and cell membranes, has pushed researchers toward the proposition and validation of simpler two- and three-dimensional membrane models, whose utility and drawbacks will be discussed. This review also describes the analytical methods used to look at the interactions among bioactive compounds with biological membrane models, with a particular accent on the calorimetric techniques. These studies can be considered as a powerful tool for medicinal chemistry and pharmaceutical technology, in the steps of designing new drugs and optimizing the activity and safety profile of compounds already used in the therapy.

  5. Investigation of oxidative stress involvement in hippocampus in epilepsy model induced by pilocarpine.

    Science.gov (United States)

    Freitas, R M

    2009-10-25

    The relationship between free radical and scavenger enzymes has been found in the epileptic phenomena and reactive oxygen species have been implicated in seizure-induced neurodegeneration. Using the epilepsy model obtained by systemic administration of pilocarpine in rats, we investigated the lipid peroxidation, nitrite content, superoxide dismutase (SOD) and catalase activities in the hippocampus of rats during chronic period. The enzyme activities as well as the lipid peroxidation and nitrite concentrations were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. The superoxide dismutase and catalase activities increased during the chronic phase. In addition, lipid peroxidation and nitrite levels increased in same period in the hippocampus of animals observed during spontaneous recurrent seizures. Previous studies showed that animals presenting seizures and submitted to 24h of status epilepticus showed normal levels of superoxide dismutase and increased in catalase activities as well as an increase in hippocampal lipid peroxidation and nitrite concentrations. These results show a direct evidence of lipid peroxidation and nitrite during seizure activity that could be responsible for neuronal damage in the hippocampus of rats, during the establishment of pilocarpine model of epilepsy.

  6. An ODE for an Overloaded X Model Involving a Stochastic Averaging Principle

    CERN Document Server

    Perry, Ohad

    2010-01-01

    We study an ordinary differential equation (ODE) arising as the many-server heavy-traffic fluid limit of a sequence of overloaded Markovian queueing models with two customer classes and two service pools. The system, known as the X model in the call-center literature, operates under the fixed-queue-ratio-with-thresholds (FQR-T) control, which we proposed in a recent paper as a way for one service system to help another in face of an unanticipated overload. Each pool serves only its own class until a threshold is exceeded; then one-way sharing is activated with all customer-server assignments then driving the two queues toward a fixed ratio. For large systems, that fixed ratio is achieved approximately. The ODE describes system performance during an overload. The control is driven by a queue-difference stochastic process, which operates in a faster time scale than the queueing processes themselves, thus achieving a time-dependent steady state instantaneously in the limit. As a result, for the ODE, the driving ...

  7. Framing patient consent for student involvement in pelvic examination: a dual model of autonomy.

    Science.gov (United States)

    Carson-Stevens, Andrew; Davies, Myfanwy M; Jones, Rhiain; Chik, Aiman D Pawan; Robbé, Iain J; Fiander, Alison N

    2013-11-01

    Patient consent has been formulated in terms of radical individualism rather than shared benefits. Medical education relies on the provision of patient consent to provide medical students with the training and experience to become competent doctors. Pelvic examination represents an extreme case in which patients may legitimately seek to avoid contact with inexperienced medical students particularly where these are male. However, using this extreme case, this paper will examine practices of framing and obtaining consent as perceived by medical students. This paper reports findings of an exploratory qualitative study of medical students and junior doctors. Participants described a number of barriers to obtaining informed consent. These related to misunderstandings concerning student roles and experiences and insufficient information on the nature of the examination. Participants reported perceptions of the negative framing of decisions on consent by nursing staff where the student was male. Potentially coercive practices of framing of the decision by senior doctors were also reported. Participants outlined strategies they adopted to circumvent patients' reasons for refusal. Practices of framing the information used by students, nurses and senior doctors to enable patients to decide about consent are discussed in the context of good ethical practice. In the absence of a clear ethical model, coercion appears likely. We argue for an expanded model of autonomy in which the potential tension between respecting patients' autonomy and ensuring the societal benefit of well-trained doctors is recognised. Practical recommendations are made concerning information provision and clear delineations of student and patient roles and expectations.

  8. The necessary burden of involving stakeholders in agent-based modelling for education and decision-making

    Science.gov (United States)

    Bommel, P.; Bautista Solís, P.; Leclerc, G.

    2016-12-01

    We implemented a participatory process with water stakeholders for improving resilience to drought at watershed scale, and for reducing water pollution disputes in drought prone Northwestern Costa Rica. The purpose is to facilitate co-management in a rural watershed impacted by recurrent droughts related to ENSO. The process involved designing "ContaMiCuenca", a hybrid agent-based model where users can specify the decisions of their agents. We followed a Companion Modeling approach (www.commod.org) and organized 10 workshops that included research techniques such as participatory diagnostics, actor-resources-interaction and UML diagrams, multi-agents model design, and interactive simulation sessions. We collectively assessed the main water issues in the watershed, prioritized their importance, defined the objectives of the process, and pilot-tested ContaMiCuenca for environmental education with adults and children. Simulation sessions resulted in debates about the need to improve the model accuracy, arguably more relevant for decision-making. This helped identify sensible knowledge gaps in the groundwater pollution and aquifer dynamics that need to be addressed in order to improve our collective learning. Significant mismatches among participants expectations, objectives, and agendas considerably slowed down the participatory process. The main issue may originate in participants expecting technical solutions from a positivist science, as constantly promoted in the region by dole-out initiatives, which is incompatible with the constructivist stance of participatory modellers. This requires much closer interaction of community members with modellers, which may be hard to attain in the current research practice and institutional context. Nevertheless, overcoming these constraints is necessary for a true involvement of water stakeholders to achieve community-based decisions that facilitate integrated water management. Our findings provide significant guidance for

  9. Students' learning as the focus for shared involvement between universities and clinical practice: a didactic model for postgraduate degree projects.

    Science.gov (United States)

    Öhlén, J; Berg, L; Björk Brämberg, E; Engström, Å; German Millberg, L; Höglund, I; Jacobsson, C; Lepp, M; Lidén, E; Lindström, I; Petzäll, K; Söderberg, S; Wijk, H

    2012-10-01

    In an academic programme, completion of a postgraduate degree project could be a significant means of promoting student learning in evidence- and experience-based practice. In specialist nursing education, which through the European Bologna process would be raised to the master's level, there is no tradition of including a postgraduate degree project. The aim was to develop a didactic model for specialist nursing students' postgraduate degree projects within the second cycle of higher education (master's level) and with a specific focus on nurturing shared involvement between universities and healthcare settings. This study embodies a participatory action research and theory-generating design founded on empirically practical try-outs. The 3-year project included five Swedish universities and related healthcare settings. A series of activities was performed and a number of data sources secured. Constant comparative analysis was applied. A didactic model is proposed for postgraduate degree projects in specialist nursing education aimed at nurturing shared involvement between universities and healthcare settings. The focus of the model is student learning in order to prepare the students for participation as specialist nurses in clinical knowledge development. The model is developed for the specialist nursing education, but it is general and could be applicable to various education programmes.

  10. Modeling of glycerol-3-phosphate transporter suggests a potential 'tilt' mechanism involved in its function.

    Science.gov (United States)

    Tsigelny, Igor F; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K

    2008-10-01

    Many major facilitator superfamily (MFS) transporters have similar 12-transmembrane alpha-helical topologies with two six-helix halves connected by a long loop. In humans, these transporters participate in key physiological processes and are also, as in the case of members of the organic anion transporter (OAT) family, of pharmaceutical interest. Recently, crystal structures of two bacterial representatives of the MFS family--the glycerol-3-phosphate transporter (GlpT) and lac-permease (LacY)--have been solved and, because of assumptions regarding the high structural conservation of this family, there is hope that the results can be applied to mammalian transporters as well. Based on crystallography, it has been suggested that a major conformational "switching" mechanism accounts for ligand transport by MFS proteins. This conformational switch would then allow periodic changes in the overall transporter configuration, resulting in its cyclic opening to the periplasm or cytoplasm. Following this lead, we have modeled a possible "switch" mechanism in GlpT, using the concept of rotation of protein domains as in the DynDom program17 and membranephilic constraints predicted by the MAPAS program.(23) We found that the minima of energies of intersubunit interactions support two alternate positions consistent with their transport properties. Thus, for GlpT, a "tilt" of 9 degrees -10 degrees rotation had the most favorable energetics of electrostatic interaction between the two halves of the transporter; moreover, this confirmation was sufficient to suggest transport of the ligand across the membrane. We conducted steered molecular dynamics simulations of the GlpT-ligand system to explore how glycerol-3-phosphate would be handled by the "tilted" structure, and obtained results generally consistent with experimental mutagenesis data. While biochemical data remain most consistent with a single-site alternating access model, our results raise the possibility that, while the

  11. COMPUTATIONAL MODELING AND DRUG DESIGNING OF LIPOPROTEIN LIPASE (LPL INVOLVED IN ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    Maryam Torabizadeh

    2012-12-01

    Full Text Available Homology modeling and flexible docking of Lipoprotein Lipase has been studied in silico approach. Blast result was found to have similarity with Lipoprotein Lipase of 83% identity with 1LPA. Active site of LPL protein was identified by CASTP. Large potential drugs were designed for identifying molecules that can likely bind to protein target of interest. The different drug derivatives designed were used for docking with the generated structure, among the 10 derivatives designed, 3rd derivative showed highest docking result. The drug derivatives were docked to the protein by hydrogen bonding interactions and these interactions play an important role in the binding studies. Our investigations may be helpful for further studies.

  12. Circadian abnormalities in mouse models of Smith-Magenis syndrome: evidence for involvement of RAI1.

    Science.gov (United States)

    Lacaria, Melanie; Gu, Wenli; Lupski, James R

    2013-07-01

    Smith-Magenis syndrome (SMS; OMIM 182290) is a genomic disorder characterized by multiple congenital anomalies, intellectual disability, behavioral abnormalities, and disordered sleep resulting from an ~3.7 Mb deletion copy number variant (CNV) on chromosome 17p11.2 or from point mutations in the gene RAI1. The reciprocal duplication of this region results in another genomic disorder, Potocki-Lupski syndrome (PTLS; OMIM 610883), characterized by autism, intellectual disability, and congenital anomalies. We previously used chromosome-engineering and gene targeting to generate mouse models for PTLS (Dp(11)17/+), and SMS due to either deletion CNV or gene knock-out (Df(11)17-2/+ and Rai1(+/-) , respectively) and we observed phenotypes in these mouse models consistent with their associated human syndromes. To investigate the contribution of individual genes to the circadian phenotypes observed in SMS, we now report the analysis of free-running period lengths in Rai1(+/-) and Df(11)17-2/+ mice, as well as in mice deficient for another known circadian gene mapping within the commonly deleted/duplicated region, Dexras1, and we compare these results to those previously observed in Dp(11)17/+ mice. Reduced free-running period lengths were seen in Df(11)17-2/+, Rai1(+/-) , and Dexras1(-/-) , but not Dexras1(+/-) mice, suggesting that Rai1 may be the primary gene underlying the circadian defects in SMS. However, we cannot rule out the possibility that cis effects between multiple haploinsufficient genes in the SMS critical interval (e.g., RAI1 and DEXRAS1) either exacerbate the circadian phenotypes observed in SMS patients with deletions or increase their penetrance in certain environments. This study also confirms a previous report of abnormal circadian function in Dexras1(-/-) mice.

  13. microRNAs Involved in Regulating Spontaneous Recovery in Embolic Stroke Model.

    Directory of Open Access Journals (Sweden)

    Fu Jia Liu

    Full Text Available To date, miRNA expression studies on cerebral ischemia in both human and animal models have focused mainly on acute phase of ischemic stroke. In this study, we present the roles played by microRNAs in the spontaneous recovery phases in cerebral ischemia using rodent stroke models. Brain tissues were harvested at different reperfusion time points ranging from 0-168 hrs after middle cerebral artery occlusion using homologous emboli. MiRNA and mRNA expression profiles were investigated by microarray followed by multiple statistical analysis. Candidate transcripts were also validated by quantitative RT-PCR. Three specific groups of miRNAs were observed among a total of 346 differentially expressed miRNAs. miRNAs, miR-21, -142-3p, -142-5p, and -146a displayed significant upregulation during stroke recovery (48 hrs to 168 hrs compared with those during acute phases (0 hrs to 24 hrs. On the other hand, an opposite trend was observed in the expression of miR-196a/b/c, -224 and -324-3p. Interestingly, miR-206, -290, -291a-5p and -30c-1*, positively correlated with the infarct sizes, with an initial increase up to 24hrs followed by a gradual decrease from 48 hrs to 168 hrs (R = 0.95. Taken together with the expression levels of corresponding mRNA targets, we have also found that Hedgehog, Notch, Wnt and TGF-β signaling pathways could play significant roles in stroke recovery and especially in neuronal repair.

  14. Involvement of innate and adaptive immunity in a murine model of coronary arteritis mimicking Kawasaki disease.

    Science.gov (United States)

    Schulte, Danica J; Yilmaz, Atilla; Shimada, Kenichi; Fishbein, Michael C; Lowe, Emily L; Chen, Shuang; Wong, Michelle; Doherty, Terence M; Lehman, Thomas; Crother, Timothy R; Sorrentino, Rosalinda; Arditi, Moshe

    2009-10-15

    Kawasaki disease (KD) is the most common cause of acquired cardiac disease and acute vasculitis in children in the developed world. Injection of a cell wall extract isolated from Lactobacillus casei (LCCWE) into mice causes a focal coronary arteritis that histopathologically mimics the coronary lesions observed in KD patients. In this study we used this model to investigate the participation of T cells, B cells, and dendritic cells (DC) in the development of coronary arteritis. RAG1(-/-), B cell(null), and wild-type (WT) mice were injected with a single dose of LCCWE (500 microg/mouse i.p.). None of the RAG1(-/-) mice developed coronary arteritis, whereas 70% of WT and 100% of B cell(null) mice developed coronary lesions, indicating that T cells were required for lesion formation. When splenocytes isolated from LCCWE-treated mice were restimulated with LCCWE, we observed significant IFN-gamma secretion in WT but not in RAG1(-/-) mice. Immunohistochemical staining showed F4/80(+) macrophages, activated MIDC-8(+) myeloid DCs (mDC), plasmacytoid DCs, and colocalization of CD3(+) T cells with mDCs in coronary artery lesions, suggesting an Ag-driven process. T cells but not B cells are required for LCCWE-induced coronary arteritis. Similar to human lesions, the coronary lesions contain macrophages, activated mDCs, and plaslmacytoid DCs all in close proximity to T cells, further strengthening the relevance of this mouse model to the immunopathology of coronary disease in KD. These studies are consistent with the interpretation that macrophages and DCs may collaborate with T cells in the pathological mechanisms of coronary arteritis.

  15. How to develop, validate, and compare clinical prediction models involving radiological parameters: Study design and statistical methods

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kyung Hwa; Choi, Byoung Wook [Dept. of Radiology, and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Song, Ki Jun [Dept. of Biostatistics and Medical Informatics, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    Clinical prediction models are developed to calculate estimates of the probability of the presence/occurrence or future course of a particular prognostic or diagnostic outcome from multiple clinical or non-clinical parameters. Radiologic imaging techniques are being developed for accurate detection and early diagnosis of disease, which will eventually affect patient outcomes. Hence, results obtained by radiological means, especially diagnostic imaging, are frequently incorporated into a clinical prediction model as important predictive parameters, and the performance of the prediction model may improve in both diagnostic and prognostic settings. This article explains in a conceptual manner the overall process of developing and validating a clinical prediction model involving radiological parameters in relation to the study design and statistical methods. Collection of a raw dataset; selection of an appropriate statistical model; predictor selection; evaluation of model performance using a calibration plot, Hosmer-Lemeshow test and c-index; internal and external validation; comparison of different models using c-index, net reclassification improvement, and integrated discrimination improvement; and a method to create an easy-to-use prediction score system will be addressed. This article may serve as a practical methodological reference for clinical researchers.

  16. Networks involved in olfaction and their dynamics using independent component analysis and unified structural equation modeling.

    Science.gov (United States)

    Karunanayaka, Prasanna; Eslinger, Paul J; Wang, Jian-Li; Weitekamp, Christopher W; Molitoris, Sarah; Gates, Kathleen M; Molenaar, Peter C M; Yang, Qing X

    2014-05-01

    The study of human olfaction is complicated by the myriad of processing demands in conscious perceptual and emotional experiences of odors. Combining functional magnetic resonance imaging with convergent multivariate network analyses, we examined the spatiotemporal behavior of olfactory-generated blood-oxygenated-level-dependent signal in healthy adults. The experimental functional magnetic resonance imaging (fMRI) paradigm was found to offset the limitations of olfactory habituation effects and permitted the identification of five functional networks. Analysis delineated separable neuronal circuits that were spatially centered in the primary olfactory cortex, striatum, dorsolateral prefrontal cortex, rostral prefrontal cortex/anterior cingulate, and parietal-occipital junction. We hypothesize that these functional networks subserve primary perceptual, affective/motivational, and higher order olfactory-related cognitive processes. Results provided direct evidence for the existence of parallel networks with top-down modulation for olfactory processing and clearly distinguished brain activations that were sniffing-related versus odor-related. A comprehensive neurocognitive model for olfaction is presented that may be applied to broader translational studies of olfactory function, aging, and neurological disease.

  17. Proteins involved in the degradation of cytoplasmic mRNA in the major eukaryotic model systems.

    Science.gov (United States)

    Siwaszek, Aleksandra; Ukleja, Marta; Dziembowski, Andrzej

    2014-01-01

    The process of mRNA decay and surveillance is considered to be one of the main posttranscriptional gene expression regulation platforms in eukaryotes. The degradation of stable, protein-coding transcripts is normally initiated by removal of the poly(A) tail followed by 5'-cap hydrolysis and degradation of the remaining mRNA body by Xrn1. Alternatively, the exosome complex degrades mRNA in the 3'>5'direction. The newly discovered uridinylation-dependent pathway, which is present in many different organisms, also seems to play a role in bulk mRNA degradation. Simultaneously, to avoid the synthesis of incorrect proteins, special cellular machinery is responsible for the removal of faulty transcripts via nonsense-mediated, no-go, non-stop or non-functional 18S rRNA decay. This review is focused on the major eukaryotic cytoplasmic mRNA degradation pathways showing many similarities and pointing out main differences between the main model-species: yeast, Drosophila, plants and mammals.

  18. The Leech Nervous System: A Valuable Model to Study the Microglia Involvement in Regenerative Processes

    Directory of Open Access Journals (Sweden)

    Françoise Le Marrec-Croq

    2013-01-01

    Full Text Available Microglia are intrinsic components of the central nervous system (CNS. During pathologies in mammals, inflammatory processes implicate the resident microglia and the infiltration of blood cells including macrophages. Functions of microglia appear to be complex as they exhibit both neuroprotective and neurotoxic effects during neuropathological conditions in vivo and in vitro. The medicinal leech Hirudo medicinalis is a well-known model in neurobiology due to its ability to naturally repair its CNS following injury. Considering the low infiltration of blood cells in this process, the leech CNS is studied to specify the activation mechanisms of only resident microglial cells. The microglia recruitment is known to be essential for the usual sprouting of injured axons and does not require any other glial cells. The present review will describe the questions which are addressed to understand the nerve repair. They will discuss the implication of leech factors in the microglial accumulation, the identification of nerve cells producing these molecules, and the study of different microglial subsets. Those questions aim to better understand the mechanisms of microglial cell recruitment and their crosstalk with damaged neurons. The study of this dialog is necessary to elucidate the balance of the inflammation leading to the leech CNS repair.

  19. Beyond the Didactic Classroom: Educational Models to Encourage Active Student Involvement in Learning

    Science.gov (United States)

    Shreeve, Michael W.

    2008-01-01

    In a chiropractic college that utilizes a hybrid curriculum model composed of adult-based learning strategies along with traditional lecture-based course delivery, a literature search for educational delivery methods that would integrate the affective domain and the cognitive domain of learning provided some insights into the use of problem-based learning (PBL), experiential learning theory (ELT), and the emerging use of appreciative inquiry (AI) to enhance the learning experience. The purpose of this literature review is to provide a brief overview of key components of PBL, ELT, and AI in educational methodology and to discuss how these might be used within the chiropractic curriculum to supplement traditional didactic lecture courses. A growing body of literature describes the use of PBL and ELT in educational settings across many disciplines, both at the undergraduate and graduate levels. The use of appreciative inquiry as an instructional methodology presents a new area for exploration and study in the academic environment. Educational research in the chiropractic classroom incorporating ELT and appreciative inquiry might provide some valuable insights for future curriculum development. PMID:18483586

  20. Beyond the didactic classroom: educational models to encourage active student involvement in learning.

    Science.gov (United States)

    Shreeve, Michael W

    2008-01-01

    In a chiropractic college that utilizes a hybrid curriculum model composed of adult-based learning strategies along with traditional lecture-based course delivery, a literature search for educational delivery methods that would integrate the affective domain and the cognitive domain of learning provided some insights into the use of problem-based learning (PBL), experiential learning theory (ELT), and the emerging use of appreciative inquiry (AI) to enhance the learning experience. The purpose of this literature review is to provide a brief overview of key components of PBL, ELT, and AI in educational methodology and to discuss how these might be used within the chiropractic curriculum to supplement traditional didactic lecture courses. A growing body of literature describes the use of PBL and ELT in educational settings across many disciplines, both at the undergraduate and graduate levels. The use of appreciative inquiry as an instructional methodology presents a new area for exploration and study in the academic environment. Educational research in the chiropractic classroom incorporating ELT and appreciative inquiry might provide some valuable insights for future curriculum development.

  1. Analysis of two-body nonleptonic B decays involving light mesons in the standard model

    Science.gov (United States)

    Ali, A.; Greub, C.

    1998-03-01

    We report a theoretical analysis of the exclusive nonleptonic decays of the B+/- and B0 mesons into two light mesons, some of which have been measured recently by the CLEO Collaboration. Our analysis is carried out in the context of an effective Hamiltonian based on the standard model (SM), using next-to-leading order perturbative QCD calculations. We explicitly take into account the O(αs) penguin-loop diagrams of all four-Fermi operators and the O(αs) tree-level diagram of the chromomagnetic dipole operator, and give a prescription for including their effects in nonleptonic two-body decays. Using a factorization ansatz for the hadronic matrix elements, we show that existing data, in particular, the branching ratios B(B+/--->η'K+/-), B(B+/--->π+/-K0), B(B0(B0¯)-->π-/+K+/-), and B(B+/--->ωh+/-)(h+/-=π+/-,K+/-), can be accounted for in this approach. Thus, theoretical scenarios with a substantially enhanced Wilson coefficient of the chromomagnetic dipole operator (as compared to the SM) and/or those with a substantial color-singlet cc¯ component in the wave function of η' are not required by these data. We predict, among other decay rates, the branching ratios for the decays B0(B0¯)-->π+/-π-/+ and B+/--->π0π+/-, which are close to the present experimental limits. Implications of some of these measurements for the parameters of the CKM matrix are presented.

  2. The Undergraduate ALFALFA Team: A Model for Involving Undergraduates in Major Legacy Astronomy Research

    Science.gov (United States)

    Troischt, Parker; Koopmann, Rebecca A.; Haynes, Martha P.; Higdon, Sarah; Balonek, Thomas J.; Cannon, John M.; Coble, Kimberly A.; Craig, David; Durbala, Adriana; Finn, Rose; Hoffman, G. Lyle; Kornreich, David A.; Lebron, Mayra E.; Crone-Odekon, Mary; O'Donoghue, Aileen A.; Olowin, Ronald Paul; Pantoja, Carmen; Rosenberg, Jessica L.; Venkatesan, Aparna; Wilcots, Eric M.; Alfalfa Team

    2015-01-01

    The NSF-sponsored Undergraduate ALFALFA (Arecibo Legacy Fast ALFA) Team (UAT) is a consortium of 19 institutions founded to promote undergraduate research and faculty development within the extragalactic ALFALFA HI blind survey project and follow-up programs. The collaborative nature of the UAT allows faculty and students from a wide ​range of public and private colleges and especially those with small astronomy programs to develop scholarly collaborations. Components of the program include an annual undergraduate workshop at Arecibo Observatory, observing runs at Arecibo, computer infrastructure, summer and academic year research projects, and dissemination at national meetings (e.g., Alfvin et al., Martens et al., Sanders et al., this meeting). Through this model, faculty and students are learning how science is accomplished in a large collaboration while contributing to the scientific goals of a major legacy survey. In the 7 years of the program, 23 faculty and more than 220 undergraduate students have participated at a significant level. 40% of them have been women and members of underrepresented groups. Faculty, many of whom were new to the collaboration and had expertise in other fields, contribute their diverse sets of skills to ALFALFA ​related projects via observing, data reduction, collaborative research, and research with students. 142 undergraduate students have attended the annual workshops at Arecibo Observatory, interacting with faculty, graduate students, their peers, and Arecibo staff in lectures, group activities, tours, and observing runs. Team faculty have supervised 131 summer research projects and 94 academic year (e.g., senior thesis) projects. 62 students have traveled to Arecibo Observatory for observing runs and 46 have presented their results at national meetings. 93% of alumni are attending graduate school and/or pursuing a career in STEM. Half of those pursuing graduate degrees in Physics or Astronomy are women. This work has been

  3. A model approach to vanadium involvement in crude oils and their refining. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Christou, G.

    1994-04-01

    Heavy crude oils contain a large amount of metal impurities, primarily vanadium species. These comprise both vanadyl porphyrins and vanadyl non-porphyrins. During hydrotreating of crude oils (reaction with H{sub 2} over a supported Mo/S catalyst at 350-- 450{degrees}C) for upgrading to usable products the V impurities are converted to insoluble V sulfides which help poison the fixed-bed Mo catalyst. Very little is known about the chemistry occurring at a detailed level; basically, it is known that initial impurities are vanadyl (VO){sup 2+}, i.e., V{sup IV} species, and that during the refining processes they are reduced and sulfided into polymers, i.e., the metal is reduced from V{sup IV} to {approximately} V{sup III}, the oxo is lost, the organic ligation is lost, and the metal is sulfided. In what order and in precisely what manner this overall transformation is occurring is not known. The essence of our research efforts is to develop vanadium chemistry of relevance to this area and to thereby provide fundamental information on the transformations occurring and that might prove useful in catalyst design. Our work has encompassed the study of the reactivity chemistry of [VO]{sup 2+} species and the formation and characterization of V/S aggregates under conditions designed to mimic those present under hydrotreating conditions. Thus, we are applying an Inorganic Model Approach to provide insights into the chemistry occurring during the refining process. Our emphasis has been on definitive characterization of products using a variety of physical techniques,including X-ray crystallography. Our work covers the following areas, each of which is described: studies in V/O{sup 2+} chemistry; V{sup III}/O chemistry; V/S complexes; and absorption of [VO]{sup 2+} groups on catalyst surfaces.

  4. Can the Epstein Model of Parental Involvement Work in a High-Minority, High-Poverty Elementary School? A Case Study

    Science.gov (United States)

    Bower, Heather A.; Griffin, Dana

    2011-01-01

    The literature has lauded parental involvement as an effective strategy to increase student achievement, but schools still struggle with how to effectively involve parents of color and low-income families. In an effort to assess the effectiveness of the Epstein Model of Parental Involvement in high-poverty, high-minority schools, the authors…

  5. Can the Epstein Model of Parental Involvement Work in a High-Minority, High-Poverty Elementary School? A Case Study

    Science.gov (United States)

    Bower, Heather A.; Griffin, Dana

    2011-01-01

    The literature has lauded parental involvement as an effective strategy to increase student achievement, but schools still struggle with how to effectively involve parents of color and low-income families. In an effort to assess the effectiveness of the Epstein Model of Parental Involvement in high-poverty, high-minority schools, the authors…

  6. Multiscale method for modeling binding phenomena involving large objects: application to kinesin motor domains motion along microtubules.

    Science.gov (United States)

    Li, Lin; Alper, Joshua; Alexov, Emil

    2016-03-18

    Many biological phenomena involve the binding of proteins to a large object. Because the electrostatic forces that guide binding act over large distances, truncating the size of the system to facilitate computational modeling frequently yields inaccurate results. Our multiscale approach implements a computational focusing method that permits computation of large systems without truncating the electrostatic potential and achieves the high resolution required for modeling macromolecular interactions, all while keeping the computational time reasonable. We tested our approach on the motility of various kinesin motor domains. We found that electrostatics help guide kinesins as they walk: N-kinesins towards the plus-end, and C-kinesins towards the minus-end of microtubules. Our methodology enables computation in similar, large systems including protein binding to DNA, viruses, and membranes.

  7. Identification of protein networks involved in the disease course of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Annelies Vanheel

    Full Text Available A more detailed insight into disease mechanisms of multiple sclerosis (MS is crucial for the development of new and more effective therapies. MS is a chronic inflammatory autoimmune disease of the central nervous system. The aim of this study is to identify novel disease associated proteins involved in the development of inflammatory brain lesions, to help unravel underlying disease processes. Brainstem proteins were obtained from rats with MBP induced acute experimental autoimmune encephalomyelitis (EAE, a well characterized disease model of MS. Samples were collected at different time points: just before onset of symptoms, at the top of the disease and following recovery. To analyze changes in the brainstem proteome during the disease course, a quantitative proteomics study was performed using two-dimensional difference in-gel electrophoresis (2D-DIGE followed by mass spectrometry. We identified 75 unique proteins in 92 spots with a significant abundance difference between the experimental groups. To find disease-related networks, these regulated proteins were mapped to existing biological networks by Ingenuity Pathway Analysis (IPA. The analysis revealed that 70% of these proteins have been described to take part in neurological disease. Furthermore, some focus networks were created by IPA. These networks suggest an integrated regulation of the identified proteins with the addition of some putative regulators. Post-synaptic density protein 95 (DLG4, a key player in neuronal signalling and calcium-activated potassium channel alpha 1 (KCNMA1, involved in neurotransmitter release, are 2 putative regulators connecting 64% of the identified proteins. Functional blocking of the KCNMA1 in macrophages was able to alter myelin phagocytosis, a disease mechanism highly involved in EAE and MS pathology. Quantitative analysis of differentially expressed brainstem proteins in an animal model of MS is a first step to identify disease-associated proteins and

  8. Identification of genes and pathways involved in retinal neovascularization by microarray analysis of two animal models of retinal angiogenesis.

    Science.gov (United States)

    Recchia, Franco M; Xu, Lili; Penn, John S; Boone, Braden; Dexheimer, Phillip J

    2010-02-01

    Comparative retinal gene expression analysis in two rodent models of oxygen-induced retinopathy (OIR) was performed to identify the genes and pathways involved in retinal neovascularization. Three independent experimental runs were conducted for each species, according to standard protocols for induction of OIR. Total retinal RNA was isolated at two time points, corresponding to the early response to relative hypoxia (P13 in mouse, P15 in rat) and to the later phase of maximum retinal neovascularization (P18 in mouse, P20 in rat) and was used to prepare labeled probes for hybridization. Gene expression was compared between normal and experimental conditions for each species at each time point. Probesets with a false-discovery rate of models. At the later time point, there were changes in 26 genes in the rat and in 1622 in the mouse, with 13 in common. Four pathways were identified in both models. Genes and pathways known to be involved in angiogenesis, as well as other biologically plausible genes and pathways, were identified. This work serves as a comprehensive resource for the study of retinal neovascularization and identification of potential rational targets for antiangiogenic therapy.

  9. Differential expression of genes involved in the degeneration and regeneration pathways in mouse models for muscular dystrophies.

    Science.gov (United States)

    Onofre-Oliveira, P C G; Santos, A L F; Martins, P M; Ayub-Guerrieri, D; Vainzof, M

    2012-03-01

    The genetically determined muscular dystrophies are caused by mutations in genes coding for muscle proteins. Differences in the phenotypes are mainly the age of onset and velocity of progression. Muscle weakness is the consequence of myofiber degeneration due to an imbalance between successive cycles of degeneration/regeneration. While muscle fibers are lost, a replacement of the degraded muscle fibers by adipose and connective tissues occurs. Major investigation points are to elicit the involved pathophysiological mechanisms to elucidate how each mutation can lead to a specific degenerative process and how the regeneration is stimulated in each case. To answer these questions, we used four mouse models with different mutations causing muscular dystrophies, Dmd (mdx), SJL/J, Large (myd) and Lama2 (dy2J) /J, and compared the histological changes of regeneration and fibrosis to the expression of genes involved in those processes. For regeneration, the MyoD, Myf5 and myogenin genes related to the proliferation and differentiation of satellite cells were studied, while for degeneration, the TGF-β1 and Pro-collagen 1α2 genes, involved in the fibrotic cascade, were analyzed. The result suggests that TGF-β1 gene is activated in the dystrophic process in all the stages of degeneration, while the activation of the expression of the pro-collagen gene possibly occurs in mildest stages of this process. We also observed that each pathophysiological mechanism acted differently in the activation of regeneration, with distinctions in the induction of proliferation of satellite cells, but with no alterations in stimulation to differentiation. Dysfunction of satellite cells can, therefore, be an important additional mechanism of pathogenesis in the dystrophic muscle.

  10. Zebrafish larva as a reliable model for in vivo assessment of membrane remodeling involvement in the hepatotoxicity of chemical agents.

    Science.gov (United States)

    Podechard, Normand; Chevanne, Martine; Fernier, Morgane; Tête, Arnaud; Collin, Aurore; Cassio, Doris; Kah, Olivier; Lagadic-Gossmann, Dominique; Sergent, Odile

    2016-11-28

    The easy-to-use in vivo model, zebrafish larva, is being increasingly used to screen chemical-induced hepatotoxicity, with a good predictivity for various mechanisms of liver injury. However, nothing is known about its applicability in exploring the mechanism called membrane remodeling, depicted as changes in membrane fluidity or lipid raft properties. The aim of this study was, therefore, to substantiate the zebrafish larva as a suitable in vivo model in this context. Ethanol was chosen as a prototype toxicant because it is largely described, both in hepatocyte cultures and in rodents, as capable of inducing a membrane remodeling leading to hepatocyte death and liver injury. The zebrafish larva model was demonstrated to be fully relevant as membrane remodeling was maintained even after a 1-week exposure without any adaptation as usually reported in rodents and hepatocyte cultures. It was also proven to exhibit a high sensitivity as it discriminated various levels of cytotoxicity depending on the extent of changes in membrane remodeling. In this context, its sensitivity appeared higher than that of WIF-B9 hepatic cells, which is suited for analyzing this kind of hepatotoxicity. Finally, the protection afforded by a membrane stabilizer, ursodeoxycholic acid (UDCA), or by a lipid raft disrupter, pravastatin, definitely validated zebrafish larva as a reliable model to quickly assess membrane remodeling involvement in chemical-induced hepatotoxicity. In conclusion, this model, compatible with a high throughput screening, might be adapted to seek hepatotoxicants via membrane remodeling, and also drugs targeting membrane features to propose new preventive or therapeutic strategies in chemical-induced liver diseases. Copyright © 2016 John Wiley & Sons, Ltd.

  11. A hidden Markov model to identify and adjust for selection bias: an example involving mixed migration strategies.

    Science.gov (United States)

    Fieberg, John R; Conn, Paul B

    2014-05-01

    An important assumption in observational studies is that sampled individuals are representative of some larger study population. Yet, this assumption is often unrealistic. Notable examples include online public-opinion polls, publication biases associated with statistically significant results, and in ecology, telemetry studies with significant habitat-induced probabilities of missed locations. This problem can be overcome by modeling selection probabilities simultaneously with other predictor-response relationships or by weighting observations by inverse selection probabilities. We illustrate the problem and a solution when modeling mixed migration strategies of northern white-tailed deer (Odocoileus virginianus). Captures occur on winter yards where deer migrate in response to changing environmental conditions. Yet, not all deer migrate in all years, and captures during mild years are more likely to target deer that migrate every year (i.e., obligate migrators). Characterizing deer as conditional or obligate migrators is also challenging unless deer are observed for many years and under a variety of winter conditions. We developed a hidden Markov model where the probability of capture depends on each individual's migration strategy (conditional versus obligate migrator), a partially latent variable that depends on winter severity in the year of capture. In a 15-year study, involving 168 white-tailed deer, the estimated probability of migrating for conditional migrators increased nonlinearly with an index of winter severity. We estimated a higher proportion of obligates in the study cohort than in the population, except during a span of 3 years surrounding back-to-back severe winters. These results support the hypothesis that selection biases occur as a result of capturing deer on winter yards, with the magnitude of bias depending on the severity of winter weather. Hidden Markov models offer an attractive framework for addressing selection biases due to their

  12. Treadmill Exercise Prevents Increase of Neuroinflammation Markers Involved in the Dopaminergic Damage of the 6-OHDA Parkinson's Disease Model.

    Science.gov (United States)

    Real, Caroline Cristiano; Garcia, Priscila Crespo; Britto, Luiz R G

    2017-08-11

    Parkinson's disease (PD) involves loss of dopaminergic neurons in the substantia nigra (SN), which can be correlated to neuroinflammatory changes with the aging of the nervous system. On the other hand, exercise can reduce the deleterious effects promoted by age, but the mechanism involved is still unclear. This study investigated the preventive exercise-induced changes on neuroinflammatory processes in a rat model of PD induced by unilateral striatal injections of 6-hydroxydopamine (6-OHDA). Adult male Wistar rats were divided into two groups: (1) sedentary (SED) or (2) exercised (EX), animals that did treadmill exercise three times per week, every other day, for 4 weeks prior to 6-OHDA or saline injection. The rats were then divided into four sub-groups: (1) sedentary saline (SED), (2) sedentary 6-OHDA (SED + 6-OHDA), (3) exercised saline (EX), and (4) exercised 6-OHDA (EX + 6-OHDA). Seven and 30 days after surgery, brains were collected for immunohistochemistry and immunoblotting for dopaminergic and neuroinflammatory markers into SN and striatum. The SED + 6-OHDA animals presented an increase in the astrocyte, microglial, and oxidative species activation. On the other hand, EX + 6-OHDA animals did not present neuroinflammatory responses and performed better apormorphine test. Our data suggest that treadmill exercise throughout life can markedly reduce the chances of dopamine decrease, reinforcing studies that showed a lower incidence of Parkinson's disease in patients who were active during life.

  13. Dynamic Analysis of a Predator-Prey (Pest Model with Disease in Prey and Involving an Impulsive Control Strategy

    Directory of Open Access Journals (Sweden)

    Min Zhao

    2012-01-01

    Full Text Available The dynamic behaviors of a predator-prey (pest model with disease in prey and involving an impulsive control strategy to release infected prey at fixed times are investigated for the purpose of integrated pest management. Mathematical theoretical works have been pursuing the investigation of the local asymptotical stability and global attractivity for the semitrivial periodic solution and population persistent, which depicts the threshold expression of some critical parameters for carrying out integrated pest management. Numerical analysis indicates that the impulsive control strategy has a strong effect on the dynamical complexity and population persistent using bifurcation diagrams and power spectra diagrams. These results show that if the release amount of infective prey can satisfy some critical conditions, then all biological populations will coexist. All these results are expected to be of use in the study of the dynamic complexity of ecosystems.

  14. Parental Involvement

    OpenAIRE

    Ezra S Simon

    2008-01-01

    This study was conducted in Ghana to investigate, (1) factors that predict parental involvement, (2) the relationship between parental home and school involvement and the educational achievement of adolescents, (3) the relationship between parental authoritativeness and the educational achievement of adolescent students, (4) parental involvement serving as a mediator between their authoritativeness and the educational achievement of the students, and (5) whether parental involvement decreases...

  15. Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

    Science.gov (United States)

    Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

    factors and are expressed during development, we hypothesized they may play a role newt tail regenerative morphogenesis under altered g-levels. Specifically there is increasing evidence for HSPs expression changes as a result of hyper-and microgravity. HSPs are also expressed throughout regeneration, rather than just after surgery. To test this hypothesis we performed heat shock on intact and regenerating newts and collected tail tissues. In these experiments we observed that some tails had uplifted tips while others mimicked hook-like regenerates at 1g or 2g. These findings suggest that heat shock, and HSPs induction, may be involved in the mechanism responsible for gravity effects on morphogenesis, or at least interact with them. Current work underway is focused on analyzing the expression of mRNA and localization of proteins for two members of the group, Hsp70 and Hsp90. In summary, we developed and characterized a new practical animal model in which gravity mechanostimulation at 1g, versus unloading in aquaria, causes prominent effects on newt tail regenerative morphogenesis. This model can be achieved without the use of a centrifuge, significantly simplifying its research applications. Initial results using this model suggest that induction of HSPs may be involved in gravity regulation of newt tail regenerative morphogenesis. Further research based on this simple model may help to unravel mechanisms of gravity influence relevant not only to newt tail regeneration, but also to a broad range of other biological processes in amphibian models.

  16. Molecular modeling and simulation of FabG, an enzyme involved in the fatty acid pathway of Streptococcus pyogenes.

    Science.gov (United States)

    Shafreen, Rajamohmed Beema; Pandian, Shunmugiah Karutha

    2013-09-01

    Streptococcus pyogenes (SP) is the major cause of pharyngitis accompanied by strep throat infections in humans. 3-keto acyl reductase (FabG), an important enzyme involved in the elongation cycle of the fatty acid pathway of S. pyogenes, is essential for synthesis of the cell-membrane, virulence factors and quorum sensing-related mechanisms. Targeting SPFabG may provide an important aid for the development of drugs against S. pyogenes. However, the absence of a crystal structure for FabG of S. pyogenes limits the development of structure-based drug designs. Hence, in the present study, a homology model of FabG was generated using the X-ray crystallographic structure of Aquifex aeolicus (PDB ID: 2PNF). The modeled structure was refined using energy minimization. Furthermore, active sites were predicted, and a large dataset of compounds was screened against SPFabG. The ligands were docked using the LigandFit module that is available from Discovery Studio version 2.5. From this list, 13 best hit ligands were chosen based on the docking score and binding energy. All of the 13 ligands were screened for Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties. From this, the two best descriptors, along with one descriptor that lay outside the ADMET plot, were selected for molecular dynamic (MD) simulation. In vitro testing of the ligands using biological assays further substantiated the efficacy of the ligands that were screened based on the in silico methods.

  17. Estrogen Receptor (ER-α36 Is Involved in Estrogen- and Tamoxifen-Induced Neuroprotective Effects in Ischemic Stroke Models.

    Directory of Open Access Journals (Sweden)

    Wei Zou

    Full Text Available The neuroprotection by estrogen (E2 and tamoxifen is well documented in experimental stroke models; however, the exact mechanism is unclear. A membrane-based estrogen receptor, ER-α36, has been identified. Postmenopausal-levels of E2 act through ER-α36 to induce osteoclast apoptosis due to a prolonged activation of the mitogen-activated protein kinase (MAPK/extracellular signal-related kinase (ERK signaling. We hypothesized that ER-α36 may play a role in the neuroprotective activities of estrogen and tamoxifen. Here, we studied ER-α36 expression in the brain, as well as its neuroprotective effects against oxygen and glucose deprivation (OGD in PC12 cells. We found that ER-α36 was expressed in both rat and human brain. In addition, OGD-induced cell death was prevented by l nmol/L 17β-estradiol (E2β. E2β activates the MAPK/ERK signaling pathway in PC12 cells under basal and OGD conditions by interacting with ER-α36 and also induces ER-α36 expression. Low-dose of tamoxifen up-regulated ER-α36 expression and enhanced neuronal survival in an ovariectomized ischemic stroke model. Furthermore, low-dose of tamoxifen enhanced neuroprotective effects by modulating activates or suppress ER-α36. Our results thus demonstrated that ER-α36 is involved in neuroprotective activities mediated by both estrogen and tamoxifen.

  18. Modeling retrospective attribution of responsibility to hazard-managing institutions: an example involving a food contamination incident.

    Science.gov (United States)

    Johnson, Branden B; Hallman, William K; Cuite, Cara L

    2015-03-01

    Perceptions of institutions that manage hazards are important because they can affect how the public responds to hazard events. Antecedents of trust judgments have received far more attention than antecedents of attributions of responsibility for hazard events. We build upon a model of retrospective attribution of responsibility to individuals to examine these relationships regarding five classes of institutions that bear responsibility for food safety: producers (e.g., farmers), processors (e.g., packaging firms), watchdogs (e.g., government agencies), sellers (e.g., supermarkets), and preparers (e.g., restaurants). A nationally representative sample of 1,200 American adults completed an Internet-based survey in which a hypothetical scenario involving contamination of diverse foods with Salmonella served as the stimulus event. Perceived competence and good intentions of the institution moderately decreased attributions of responsibility. A stronger factor was whether an institution was deemed (potentially) aware of the contamination and free to act to prevent or mitigate it. Responsibility was rated higher the more aware and free the institution. This initial model for attributions of responsibility to impersonal institutions (as opposed to individual responsibility) merits further development. © 2014 Society for Risk Analysis.

  19. Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions with Efavirenz Involving Simultaneous Inducing and Inhibitory Effects on Cytochromes.

    Science.gov (United States)

    Marzolini, Catia; Rajoli, Rajith; Battegay, Manuel; Elzi, Luigia; Back, David; Siccardi, Marco

    2017-04-01

    Antiretroviral drugs are among the therapeutic agents with the highest potential for drug-drug interactions (DDIs). In the absence of clinical data, DDIs are mainly predicted based on preclinical data and knowledge of the disposition of individual drugs. Predictions can be challenging, especially when antiretroviral drugs induce and inhibit multiple cytochrome P450 (CYP) isoenzymes simultaneously. This study predicted the magnitude of the DDI between efavirenz, an inducer of CYP3A4 and inhibitor of CYP2C8, and dual CYP3A4/CYP2C8 substrates (repaglinide, montelukast, pioglitazone, paclitaxel) using a physiologically based pharmacokinetic (PBPK) modeling approach integrating concurrent effects on CYPs. In vitro data describing the physicochemical properties, absorption, distribution, metabolism, and elimination of efavirenz and CYP3A4/CYP2C8 substrates as well as the CYP-inducing and -inhibitory potential of efavirenz were obtained from published literature. The data were integrated in a PBPK model developed using mathematical descriptions of molecular, physiological, and anatomical processes defining pharmacokinetics. Plasma drug-concentration profiles were simulated at steady state in virtual individuals for each drug given alone or in combination with efavirenz. The simulated pharmacokinetic parameters of drugs given alone were compared against existing clinical data. The effect of efavirenz on CYP was compared with published DDI data. The predictions indicate that the overall effect of efavirenz on dual CYP3A4/CYP2C8 substrates is induction of metabolism. The magnitude of induction tends to be less pronounced for dual CYP3A4/CYP2C8 substrates with predominant CYP2C8 metabolism. PBPK modeling constitutes a useful mechanistic approach for the quantitative prediction of DDI involving simultaneous inducing or inhibitory effects on multiple CYPs as often encountered with antiretroviral drugs.

  20. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    Energy Technology Data Exchange (ETDEWEB)

    Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

    2014-09-15

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

  1. Human amniotic fluid stem cells as a model for functional studies of genes involved in human genetic diseases or oncogenesis.

    Science.gov (United States)

    Rosner, Margit; Dolznig, Helmut; Schipany, Katharina; Mikula, Mario; Brandau, Oliver; Hengstschläger, Markus

    2011-09-01

    functions in AFS cells was established. Since AFS cells are not tumorigenic, gene modulations not only allow to investigate the role of endogenous genes involved in human genetic diseases but also may help to reveal putative oncogenic gene functions in different biological models, both in vitro and in vivo. This concept is discussed and a "proof of principle", already obtained via modulating genes involved in the mammalian target of rapamycin (mTOR) pathway in AFS cells, is presented.

  2. Ethnic Differences in the Effect of Parenting on Gang Involvement and Gang Delinquency: A Longitudinal, Hierarchical Linear Modeling Perspective.

    Science.gov (United States)

    Walker-Barnes, Chanequa J.; Mason, Craig A.

    2001-01-01

    Examined relative influence of peer and parenting behavior on changes in adolescent gang involvement and gang-related delinquency among ninth-graders. Found that gang involvement decreased over the school year, with average levels of gang delinquency remaining constant. Gang involvement and gang-related delinquency were most strongly predicted by…

  3. Computational modeling of chemical reactions and interstitial growth and remodeling involving charged solutes and solid-bound molecules.

    Science.gov (United States)

    Ateshian, Gerard A; Nims, Robert J; Maas, Steve; Weiss, Jeffrey A

    2014-10-01

    Mechanobiological processes are rooted in mechanics and chemistry, and such processes may be modeled in a framework that couples their governing equations starting from fundamental principles. In many biological applications, the reactants and products of chemical reactions may be electrically charged, and these charge effects may produce driving forces and constraints that significantly influence outcomes. In this study, a novel formulation and computational implementation are presented for modeling chemical reactions in biological tissues that involve charged solutes and solid-bound molecules within a deformable porous hydrated solid matrix, coupling mechanics with chemistry while accounting for electric charges. The deposition or removal of solid-bound molecules contributes to the growth and remodeling of the solid matrix; in particular, volumetric growth may be driven by Donnan osmotic swelling, resulting from charged molecular species fixed to the solid matrix. This formulation incorporates the state of strain as a state variable in the production rate of chemical reactions, explicitly tying chemistry with mechanics for the purpose of modeling mechanobiology. To achieve these objectives, this treatment identifies the specific theoretical and computational challenges faced in modeling complex systems of interacting neutral and charged constituents while accommodating any number of simultaneous reactions where reactants and products may be modeled explicitly or implicitly. Several finite element verification problems are shown to agree with closed-form analytical solutions. An illustrative tissue engineering analysis demonstrates tissue growth and swelling resulting from the deposition of chondroitin sulfate, a charged solid-bound molecular species. This implementation is released in the open-source program FEBio ( www.febio.org ). The availability of this framework may be particularly beneficial to optimizing tissue engineering culture systems by examining the

  4. Transition from 'model-based' to 'model-free' behavioral control in addiction: Involvement of the orbitofrontal cortex and dorsolateral striatum.

    Science.gov (United States)

    Lucantonio, Federica; Caprioli, Daniele; Schoenbaum, Geoffrey

    2014-01-01

    Cocaine addiction is a complex and multidimensional process involving a number of behavioral and neural forms of plasticity. The behavioral transition from voluntary drug use to compulsive drug taking may be explained at the neural level by drug-induced changes in function or interaction between a flexible planning system, associated with prefrontal cortical regions, and a rigid habit system, associated with the striatum. The dichotomy between these two systems is operationalized in computational theory by positing model-based and model-free learning mechanisms, the former relying on an "internal model" of the environment and the latter on pre-computed or cached values to control behavior. In this review, we will suggest that model-free and model-based learning mechanisms appear to be differentially affected, at least in the case of psychostimulants such as cocaine, with the former being enhanced while the latter are disrupted. As a result, the behavior of long-term drug users becomes less flexible and responsive to the desirability of expected outcomes and more habitual, based on the long history of reinforcement. To support our specific proposal, we will review recent neural and behavioral evidence on the effect of psychostimulant exposure on orbitofrontal and dorsolateral striatum structure and function. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  5. Platelets can neutralize hydrogen peroxide in an acute toxicity model with cells involved in granulation tissue formation.

    Science.gov (United States)

    Kandler, Barbara; Maitz, Philipp; Fischer, Michael B; Watzek, Georg; Gruber, Reinhard

    2005-04-01

    Platelets play a key role in the replacement of the blood clot with granulation tissue during the early steps of bone regeneration. We hypothesized that activated platelets can neutralize locally produced reactive oxygen species, thereby protecting cells involved in granulation tissue formation. The potential of platelet-released supernatant (PRS) to neutralize hydrogen peroxide (H(2)O(2)) was tested in an acute toxicity model with osteogenic, inflammatory, and endothelial cells. In the human fetal osteoblastic cell line 1.19 (hFOB), considerable morphological changes, cell shedding, and dysfunction of the respiratory chain were observed when cells were exposed to 3 mM H(2)O(2). Caspase-3 and poly-(ADP-ribose)-polymerase were not activated, suggesting that cell death occurred by necrosis. Preincubation of osteogenic cells, leukocytes, or endothelial cells with PRS decreased the acute toxicity of H(2)O(2). The capacity of platelets to release H(2)O(2)-detoxifying activity was retained for up to 72 h. Aminotriazole, an inhibitor of catalase, decreased the cytoprotective activity of PRS, whereas blocking of glutathione peroxidase by mercaptosuccinate had no effect. These results suggest that platelet-released catalase can rapidly neutralize cytotoxic amounts of H(2)O(2), a process that may play a role during the early stages of bone regeneration.

  6. Establishment of an ovarian metastasis model and possible involvement of E-cadherin down-regulation in the metastasis.

    Science.gov (United States)

    Kuwabara, Yoshiko; Yamada, Taketo; Yamazaki, Ken; Du, Wen-Lin; Banno, Kouji; Aoki, Daisuke; Sakamoto, Michiie

    2008-10-01

    Clinical observations of cases of ovarian metastasis suggest that there may be a unique mechanism underlying ovarian-specific metastasis. This study was undertaken to establish an in vivo model of metastasis to the ovary, and to investigate the mechanism of ovarian-specific metastasis. We examined the capacity for ovarian metastasis in eight different human carcinoma cell lines by implantation in female NOD/SCID mice transvenously and intraperitoneally. By transvenous inoculation, only RERF-LC-AI, a poorly differentiated carcinoma cell line, frequently demonstrated ovarian metastasis. By intraperitoneal inoculation, four of the eight cell lines (HGC27, MKN-45, KATO-III, and RERF-LC-AI) metastasized to the ovary. We compared E-cadherin expression among ovarian metastatic cell lines and others. All of these four ovarian metastatic cell lines and HSKTC, a Krukenberg tumor cell line, showed E-cadherin down-regulation and others did not. E-cadherin was then forcibly expressed in RERF-LC-AI, and inhibited ovarian metastasis completely. The capacity for metastasizing to the other organs was not affected by E-cadherin expression. We also performed histological investigation of clinical ovarian-metastatic tumor cases. About half of all ovarian-metastatic tumor cases showed loss or reduction of E-cadherin expression. These data suggest that E-cadherin down-regulation may be involved in ovarian-specific metastasis.

  7. Homology modeling and identification of amino acids involved in the catalytic process of Mycobacterium tuberculosis serine acetyltransferase.

    Science.gov (United States)

    Qiu, Juanjuan; Zang, Shizhu; Ma, Yufang; Owusu, Lawrence; Zhou, Lei; Jiang, Tao; Xin, Yi

    2017-03-01

    Serine acetyltransferase (CysE) belongs to the hexapeptide acetyltransferase family and is involved in the biosynthesis of L‑cysteine in microorganisms. Mycobacterium tuberculosis CysE is regarded as a potential target for anti‑tuberculosis (TB) drugs; however, the structure and active sites of M. tuberculosis CysE remain unknown. The present study aimed to predict the secondary structure and to construct a 3D model for M. tuberculosis CysE using bioinformatics analysis. To determine the essential amino acids that are associated with CysE enzymatic activity, amino acid sequences from several microorganisms were compared, and a consensus sequence was identified. Subsequently, site‑directed mutagenesis was used to generate mutant M. tuberculosis CysE proteins. Enzyme assays demonstrated that D67A, H82A and H117A mutants abolished ~75% activity of M. tuberculosis CysE. Prediction of the protein structure and identification of the active amino acids for M. tuberculosis CysE is essential for designing inhibitors, which may aid the discovery of effective anti‑TB drugs.

  8. GSK-3β may be involved in hippocampal mossy fiber sprouting in the pentylenetetrazole-kindling model.

    Science.gov (United States)

    Huang, Wen-Jiao; Tian, Fa-Fa; Chen, Jin-Mei; Guo, Ting-Hui; Ma, Yun-Feng; Fang, Jia; Dang, Jing; Song, Ming-Yu

    2013-11-01

    Mossy fiber sprouting (MFS) is a pathological phenomenon that is commonly observed in temporal lobe epilepsy (TLE). However, the molecular mechanisms underlying MFS remain unclear. It has been demonstrated that the tau protein is important in the progression of MFS by the regulation of microtubule dynamics and axonal transport, with all of these functions of tau modulated by its site-specific phosphorylation. Glycogen synthase kinase-3β (GSK-3β) is an active kinase that regulates the phosphorylation of tau protein. Therefore, it was hypothesized that GSK-3β contributes to MFS by phosphorylating tau protein. The aim of the present study was to determine the expression and activity of GSK-3β at different regions in the rat hippocampus during the pentylenetetrazole (PTZ)-kindling process in order to demonstrate the possible correlation with MFS, and to investigate the involvement of GSK-3β in epileptogenesis. Male Sprague-Dawley rats (n=180) were randomly divided into the control and PTZ-treated groups. The chronic epileptic model was established by intraperitoneal injection of PTZ and the hippocampus was observed for the presence of MFS using Timm staining. GSK-3β mRNA, protein and activity were analyzed in various regions of the hippocampus using in situ hybridization, immunohistochemistry and immunoprecipitation followed by a kinase assay and liquid scintillation counting, respectively. MFS was observed prior to kindling and an increased distribution of Timm granules were observed in the CA3 region of the PTZ-treated rats; however, this was not demonstrated in the supragranular layer of the dentate gyrus. The expression of GSK-3β mRNA and protein, as well as the GSK-3β activity, increased significantly from 3 days to 4 weeks in the PTZ group, and this was correlated with the progression of MFS in the CA3 area. In addition, it was demonstrated that MFS did not result from TLE. GSK-3β may therefore be involved in the progression of MFS and is important in

  9. Applying Pleck's Model of Paternal Involvement to the Study of Preschool Attachment Quality: A Proof of Concept Study

    Science.gov (United States)

    Kennedy, Mark; Betts, Lucy; Dunn, Thomas; Sonuga-Barke, Edmund; Underwood, Jean

    2015-01-01

    Recent re-conceptualisation of paternal involvement (Pleck, J. H. (2010). Paternal involvement: Revised conceptualization and theoretical linkages with child outcomes. In M. Lamb (Ed.), "The role of the father in child development" (5th ed., pp. 67-107). London: Wiley), while proving fruitful, has yet to be applied to investigations into…

  10. Autophagy and cathepsin L are involved in the antinociceptive effect of DMBC in a mouse acetic acid-writhing model

    Institute of Scientific and Technical Information of China (English)

    Wei-wei GU; Gui-zhen AO; Yong-ming ZHU; Shi-chang SUN; Qiang ZHOU; Jia-hong FAN; Katunuma NOBUHIKO

    2013-01-01

    Aim:2-(3',5'-Dimethoxybenzylidene) cyclopentanone (DMBC) is a novel synthetic compound with antinociceptive activities.The aim of this study was to investigate the roles of the autophagic-lysosomal pathway in the antinociceptive effect of DMBC in a mouse acetic acid-writhing model.Methods:Mouse acetic acid-writhing test and hotplate test were used to assess the antinociceptive effects of DMBC,3-MA (autophagy inhibitor) and Clik148 (cathepsin L inhibitor).The drugs were administered peripherally (ip) or centrally (icv).Results:Peripheral administration of 3-MA (7.5-30 mg/kg) or Clik148 (10-80 mg/kg) produced potent antinociceptive effect in acetic acid-writhing test.Central administration of 3-MA or Clik148 (12.5-50 nmol/L) produced comparable antinociceptive effect in acetic acid-writhing test.Peripheral administration of DMBC (25-50 mg/kg) produced potent antinociceptive effects in both acetic acidwrithing and hotplate tests.Furthermore,the antinociceptive effect produced by peripheral administration of DMBC (50 mg/kg) in acetic acid-writhing test was antagonized by low doses of 3-MA (3.75 mg/kg) or Clik148 (20 mg/kg) peripherally administered,but was not affected by 3-MA or Clik148 (25 nmol/L) centrally administered.Conclusion:Activation of central autophagy and cathepsin L is involved in nociception in mice,whereas peripheral autophagy and cathepsin L contributes,at least in part,to the antinociceptive effect of DMBC in mice.

  11. Head and cervical spine posture in behaving rats: implications for modeling human conditions involving the head and cervical spine.

    Science.gov (United States)

    Griffin, C; Choong, W Y; Teh, W; Buxton, A J; Bolton, P S

    2015-02-01

    The aim of this study was to define the temporal and spatial (postural) characteristics of the head and cervical vertebral column (spine) of behaving rats in order to better understand their suitability as a model to study human conditions involving the head and neck. Time spent in each of four behavioral postures was determined from video tape recordings of rats (n = 10) in the absence and presence of an intruder rat. Plain film radiographic examination of a subset of these rats (n = 5) in each of these postures allowed measurement of head and cervical vertebral column positions adopted by the rats. When single they were quadruped or crouched most (∼80%) of the time and bipedal either supported or free standing for only ∼10% of the time. The introduction of an intruder significantly (P cervical spine was orientated (median, 25-75 percentile) near vertical (18.8°, 4.2°-30.9°) when quadruped, crouched (15.4°, 7.6°-69.3°) and bipedal supported (10.5°, 4.8°-22.6°) but tended to be less vertical oriented when bipedal free standing (25.9°, 7.7°-39.3°). The range of head positions relative to the cervical spine was largest when crouched (73.4°) and smallest when erect free standing (17.7°). This study indicates that, like humans, rats have near vertical orientated cervical vertebral columns but, in contrast to humans, they displace their head in space by movements at both the cervico-thoracic junction and the cranio-cervical regions. © 2014 Wiley Periodicals, Inc.

  12. Antinociceptive effects of maprotiline in a rat model of peripheral neuropathic pain: possible involvement of opioid system

    Directory of Open Access Journals (Sweden)

    Hamid Reza Banafshe

    2015-08-01

    Conclusion: Our results suggest that maprotiline can be considered a potential therapeutic for the treatment of neuropathic pain, and the opioid system may be involved in the antihyperalgesic effects of maprotiline.

  13. Parental involvement with the criminal justice system and the effects on their children: a collaborative model for researching vulnerable families.

    Science.gov (United States)

    Akesson, Bree; Smyth, J McGregor; Mandell, Donald J; Doan, Thao; Donina, Katerina; Hoven, Christina W

    2012-01-01

    Despite the existing body of research examining the effects of imprisonment on incarcerated adults, as of yet, there is no solid empirical evidence for understanding the effects of parental involvement with the criminal justice system involvement (CJSI) on children and families. Accordingly, Columbia University-New York State's Child Psychiatric Epidemiology Group (CPEG), supported by a strong collaboration with The Bronx Defenders, a holistic public defender providing free legal representation, is conducting a longitudinal study examining the effects of parental involvement with the criminal justice system on this population. The study aims to understand, over time, the impact of parental CJSI on their children's mental health, including the effects of the collateral legal damage of CJSI (such as eviction and deportation), substance use, the development of risky behaviors leading to the child's potential involvement with the criminal justice system, as well as protective factors and identification of potential intervention points, which has the ability to inform public policy.

  14. Community involvement

    Directory of Open Access Journals (Sweden)

    Editorial Office

    1979-09-01

    Full Text Available Community involvement is the main theme of Health Year. Governments have a responsibility for the health of their people, and in this country under the present 3-tier system of government, the responsibility for the rendering of health services is divided between central, provincial and local government. However, under our democratic system, all people have the right to, and it is indeed their duty, to participate individually and collectively in the planning and implementation of services to meet their health needs. Ultimately, through involvement of individuals, families and communities, greater self-reliance is achieved leading to greater responsibility being assumed by people for their own health.

  15. Disruption of the glutamate-glutamine cycle involving astrocytes in an animal model of depression for males and females

    Directory of Open Access Journals (Sweden)

    Virginie Rappeneau

    2016-12-01

    Full Text Available Background: Women are twice as likely as men to develop major depression (MD. The brain mechanisms underlying this sex disparity are not clear. Disruption of the glutamate-glutamine cycle has been implicated in psychiatric disturbances. This study identifies sex-based impairments in the glutamate-glutamine cycle involving astrocytes using an animal model of depression. Methods: Male and female adult Long-Evans rats were exposed to chronic social defeat stress (CSDS for 21 days, using a modified resident-intruder paradigm. Territorial aggression was used for males and maternal aggression was used for females to induce depressive-like deficits for intruders. The depressive-like phenotype was assessed with intake for saccharin solution, weight gain, estrous cycle, and corticosterone (CORT. Behaviors displayed by the intruders during daily encounters with residents were characterized. Rats with daily handling were used as controls for each sex. Ten days after the last encounter, both the intruders and controls were subjected to a no-net-flux in vivo microdialysis to assess glutamate accumulation and extracellular glutamine in the nucleus accumbens (NAc. The contralateral hemispheres were used for determining changes in astrocytic markers, including glial fibrillary acidic protein (GFAP and glutamate transporter-1 (GLT-1. Results: Both male and female intruders reduced saccharin intake over the course of CSDS, compared to their pre-stress period and to their respective controls. Male intruders exhibited submissive/defensive behaviors to territorial aggression by receiving sideways threats and bites. These males showed reductions in striatal GLT-1 and spontaneous glutamine in the NAc, compared to controls. Female intruders exhibited isolated behaviors to maternal aggression, including immobility, rearing, and self-grooming. Their non-reproductive days were extended. Also, they showed reductions in prefrontal and accumbal GFAP+ cells and prefrontal GLT

  16. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas; Forestier, Erik; Frandsen, Thomas L; Harila-Saari, Arja; Heyman, Mats; Jonsson, Olafur G; Lähteenmäki, Päivi M; Lausen, Birgitte; Vaitkevičienė, Goda; Asberg, Ann; Schmiegelow, Kjeld

    2014-08-01

    Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744 patients on Nordic-Baltic trials. CNS status was classified as CNS1 (no CSF blasts), CNS2 ( 0.15). The 12-year event-free survival for patients with leukemic mass on neuroimaging did not differ from patients with negative or no scan (0.50 vs. 0.60; P = 0.7) or between patients with symptoms or signs suggestive of CNS leukemia and patients without such characteristics (0.50 vs. 0.61; P = 0.2). CNS involvement at diagnosis is associated with adverse prognostic features but does not indicate a less chemosensitive leukemia. © 2014 Wiley Periodicals, Inc.

  17. An MCDA and GIS coupling conceptual model to be used in a circular decision process by stakeholders involved in large wind farm projects

    Energy Technology Data Exchange (ETDEWEB)

    Vazquez, M. [Quebec Univ., Rimouski, PQ (Canada). Laboratoire de Recherche en Energie Eolienne; Quebec Univ., Montreal, PQ (Canada). GEIGER; Waaub, J.P. [Quebec Univ., Montreal, PQ (Canada). GEIGER; Ilinca, A. [Quebec Univ., Rimouski, PQ (Canada). Laboratoire de Recherche en Energie Eolienne

    2010-07-01

    This poster presentation described an MCDA and geographic information system (GIS) coupling conceptual model designed for use in stakeholder decision-making processes for large wind farm projects. The model was comprised of 4 modules and 4 stakeholder categories that considered the environment and communities involved in the project. The integrated modelling approach was designed to ensure a transparent decision-making process. The modules included: (1) an MCDA module, (2) a local expertise and scientific knowledge module, (3) a stakeholder involvement module, and (4) a participatory GIS module. The model can be used to structure issues during consultation procedures, as well as to conduct preference analyses and to identify indicators. Examples of stakeholder weighting were included. tabs., figs.

  18. Models predicting non-sentinel node involvement also predict for regional recurrence in breast cancer patients without axillary treatment

    NARCIS (Netherlands)

    Pepels, M.J.; Vestjens, J.H.; Boer, M. de; Bult, P.; Dijck, J.A.A.M. van; Menke-Pluijmers, M.; Diest, P.J. van; Borm, G.; Tjan-Heijnen, V.C.

    2013-01-01

    BACKGROUND: Non-SN prediction models are frequently used in clinical decision making to identify patients that may not need axillary treatment, but these models still need to be validated by follow-up data. Our purpose was the validation of non-sentinel node (SN) prediction models in predicting

  19. The Relationship between School Leaders' Perceptions of High Involvement Model Characteristics in Their Organizations and Their Attitudes towards the Use of the Change Toolkit to Facilitate Organizational Change

    Science.gov (United States)

    Kelly, Mary T.

    2009-01-01

    The purpose of this study was to investigate whether there was a relationship between school leaders' perceptions regarding High Involvement Model variables as components of their organizations, including power, knowledge, information, leadership, instructional guidance, rewards, and resources, and the leaders' ability to successfully use the IBM…

  20. Green spermatozoa illuminate a 30-year-old model:sperm-egg adhesion involves intra-acrosomal proteins

    Institute of Scientific and Technical Information of China (English)

    Steve Tardif

    2011-01-01

    @@ Fertilisation in mammals involves many synchronized steps including spermegg adhesion.Prior to sperm-oolemma fusion,spermatozoa need to undergo the acrosome reaction (AR) or exocytosis.The universal belief,for many years,has been that the AR was initiated upon binding to the zona pellucida (ZP).As such acrosomal proteins were not thought to be involved in the primary contact with the ZP.These proteins were only suggested to be biologically relevant once the sperm were attached to the ZP and during subsequent events.However,recent data in the mouse have unequivocally demonstrated that spermatozoa can begin exocytosis before contact with ZP.1 It is a remarkable finding as not only will the interpretation of the interaction between sperm and cumulus cells need to be revised,but the processes of capacitation,vesiculation and exposure of acrosomal content need reexamination.

  1. A six-stage model of brand loyalty for sport consumers: Integrating theories of enduring involvement, identity and loyalty

    OpenAIRE

    Argus, Kevin James

    2017-01-01

    This thesis explores the formative antecedents and stages leading to consumers’ enduring involvement (EI) and loyalty with brands and products. This aim was pursued by conducting a study of sport consumers, of varying duration and intensity of EI and loyalty. A further aim was to determine whether the motives of consumers’ transitions between these stages of EI provide insights that explain their transitions between stages of brand loyalty and/or product loyalty. Of pa...

  2. The Effects of the Behavior Analysis Model of Follow Through to Increase Native American Involvement in the Classroom Educational Process.

    Science.gov (United States)

    McLaughlin, T. F.; And Others

    1980-01-01

    The effects of the Behavior Analysis Model of Follow Through as to the percent of Native Americans in instructional roles were examined. Large percentage increases were found in the use of Native Americans in the classroom as a function of the adoption of the Behavior Analysis Model of Follow Through. (Author)

  3. Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer

    Science.gov (United States)

    Heger, Zbynek; Merlos Rodrigo, Miguel Angel; Michalek, Petr; Polanska, Hana; Masarik, Michal; Vit, Vitezslav; Plevova, Mariana; Pacik, Dalibor; Eckschlager, Tomas; Stiborova, Marie

    2016-01-01

    The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential. PMID:27824899

  4. Parental involvement, child effort, and the development of immigrant boys' and girls' reading and mathematics skills: A latent difference score growth model.

    Science.gov (United States)

    Moon, Ui Jeong; Hofferth, Sandra L

    2016-04-01

    Gender differences in elementary school performance among immigrant children have not yet been well documented. This study examined how differences in parental involvement, child effort, and family characteristics and resources contribute to immigrant boys'-and girls' academic achievement from kindergarten through 5(th)-grade. The sample was drawn from the Early Childhood Longitudinal Study-Kindergarten cohort. Using a latent score growth model, this study found that parents' involvement at home benefited boys' reading and mathematics skills throughout all early elementary school years, but did not have the same benefit for girls. For both boys and girls, child effort in reading appears to be strongly linked to better reading and mathematics skills at kindergarten and to subsequent improvement between grades. The positive associations of parental involvement and child's effort with test scores were greater during earlier years than during later years for boys, whereas there was no difference in the association over time for girls.

  5. Modelling dopaminergic and other processes involved in learning from reward prediction error: Contributions from an individual differences perspective

    Directory of Open Access Journals (Sweden)

    Alan David Pickering

    2014-09-01

    Full Text Available Phasic firing changes of midbrain dopamine neurons have been widely characterised as reflecting a reward prediction error (RPE. Major personality traits (e.g. extraversion have been linked to inter-individual variations in dopaminergic neurotransmission. Consistent with these two claims, recent research (Smillie, Cooper, & Pickering, 2011; Cooper, Duke, Pickering, & Smillie, 2014 found that extraverts exhibited larger RPEs than introverts, as reflected in feedback related negativity (FRN effects in EEG recordings. Using an established, biologically-localised RPE computational model, we successfully simulated dopaminergic cell firing changes which are thought to modulate the FRN. We introduced simulated individual differences into the model: parameters were systematically varied, with stable values for each simulated individual. We explored whether a model parameter might be responsible for the observed covariance between extraversion and the FRN changes in real data, and argued that a parameter is a plausible source of such covariance if parameter variance, across simulated individuals, correlated almost perfectly with the size of the simulated dopaminergic FRN modulation, and created as much variance as possible in this simulated output. Several model parameters met these criteria, while others did not. In particular, variations in the strength of connections carrying excitatory reward drive inputs to midbrain dopaminergic cells were considered plausible candidates, along with variations in a parameter which scales the effects of dopamine cell firing bursts on synaptic modification in ventral striatum. We suggest possible neurotransmitter mechanisms underpinning these model parameters. Finally, the limitations and possible extensions of our approach are discussed.

  6. Modeling dopaminergic and other processes involved in learning from reward prediction error: contributions from an individual differences perspective.

    Science.gov (United States)

    Pickering, Alan D; Pesola, Francesca

    2014-01-01

    Phasic firing changes of midbrain dopamine neurons have been widely characterized as reflecting a reward prediction error (RPE). Major personality traits (e.g., extraversion) have been linked to inter-individual variations in dopaminergic neurotransmission. Consistent with these two claims, recent research (Smillie et al., 2011; Cooper et al., 2014) found that extraverts exhibited larger RPEs than introverts, as reflected in feedback related negativity (FRN) effects in EEG recordings. Using an established, biologically-localized RPE computational model, we successfully simulated dopaminergic cell firing changes which are thought to modulate the FRN. We introduced simulated individual differences into the model: parameters were systematically varied, with stable values for each simulated individual. We explored whether a model parameter might be responsible for the observed covariance between extraversion and the FRN changes in real data, and argued that a parameter is a plausible source of such covariance if parameter variance, across simulated individuals, correlated almost perfectly with the size of the simulated dopaminergic FRN modulation, and created as much variance as possible in this simulated output. Several model parameters met these criteria, while others did not. In particular, variations in the strength of connections carrying excitatory reward drive inputs to midbrain dopaminergic cells were considered plausible candidates, along with variations in a parameter which scales the effects of dopamine cell firing bursts on synaptic modification in ventral striatum. We suggest possible neurotransmitter mechanisms underpinning these model parameters. Finally, the limitations and possible extensions of our general approach are discussed.

  7. A Blended Learning Approach to Teaching Project Management: A Model for Active Participation and Involvement: Insights from Norway

    Directory of Open Access Journals (Sweden)

    Bassam A. Hussein

    2015-04-01

    Full Text Available The paper demonstrates and evaluates the effectiveness of a blended learning approach to create a meaningful learning environment. We use the term blended learning approach in this paper to refer to the use of multiple or hybrid instructional methods that emphasize the role of learners as contributors to the learning process rather than recipients of learning. Contribution to learning is attained by using in class gaming as pathways that ensure active involvement of learners. Using a blended learning approach is important in order to be able to address different learning styles of the target group. The approach was also important in order to be able to demonstrate different types of challenges, issues and competences needed in project management. Student evaluations of the course confirmed that the use of multiple learning methods and, in particular, in class gaming was beneficial and contributed to a meaningful learning experience.

  8. Intestinal epithelial restitution. Involvement of specific laminin isoforms and integrin laminin receptors in wound closure of a transformed model epithelium

    DEFF Research Database (Denmark)

    Lotz, M M; Nusrat, A; Madara, J L;

    1997-01-01

    Disruptions in the mucosal lining of the gastrointestinal tract reseal by epithelial cell migration, a process termed restitution. We examined the involvement of laminin isoforms and their integrin receptors in restitution using the intestinal epithelial cell line T84. T84 cells express primarily...... laminins 5, 6, and 7 as indicated by immunostaining using laminin subunit-specific monoclonal antibodies (MAbs). A MAb (BM2) specific for the laminin alpha 3 subunit, a component of laminins 5, 6, and 7, completely inhibited the closure of mechanical wounds in T84 monolayers. Confocal microscopy using MAbs...... BM2 (laminin alpha 3 subunit) and 6F12 (laminin beta 3 subunit) revealed that laminin-5 is deposited in a basal matrix that extends into the wound. The MAbs 4E10 (laminin beta 1 subunit) and C4 (laminin beta 2 subunit) stained the lateral membranes between T84 cells. This staining was enhanced...

  9. Exploring the experiences of client involvement in medication decisions using a shared decision making model: results of a qualitative study.

    Science.gov (United States)

    Goscha, Richard; Rapp, Charles

    2015-04-01

    This qualitative study explored a newly introduced model of shared decision making (CommonGround) and how psychiatric medications were experienced by clients, prescribers, case managers and peer support staff. Of the twelve client subjects, six were highly engaged in shared decision-making and six were not. Five notable differences were found between the two groups including the presence of a goal, use of personal medicine, and the behavior of case managers and prescribers. Implications for a shared decision making model in psychiatry are discussed.

  10. A Heterogeneous Bayesian Regression Model for Cross-Sectional Data Involving a Single Observation per Response Unit

    Science.gov (United States)

    Fong, Duncan K. H.; Ebbes, Peter; DeSarbo, Wayne S.

    2012-01-01

    Multiple regression is frequently used across the various social sciences to analyze cross-sectional data. However, it can often times be challenging to justify the assumption of common regression coefficients across all respondents. This manuscript presents a heterogeneous Bayesian regression model that enables the estimation of…

  11. Youth Activity Involvement, Neighborhood Adult Support, Individual Decision Making Skills, and Early Adolescent Delinquent Behaviors: Testing a Conceptual Model

    Science.gov (United States)

    Crean, Hugh F.

    2012-01-01

    This study examines a cross-sectional structural equation model of participation in youth activities, neighborhood adult support, individual decision making skills, and delinquent behavior in urban middle school youths (n = 2611). Results indicate extracurricular activity participation had both direct and indirect associations with delinquent…

  12. Involvement of receptor tyrosine kinase Tyro3 in amyloidogenic APP processing and β-amyloid deposition in Alzheimer's disease models.

    Directory of Open Access Journals (Sweden)

    Yan Zheng

    Full Text Available Alzheimer's disease (AD is the most common progressive neurodegenerative disease known to humankind. It is characterized by brain atrophy, extracellular amyloid plaques, and intracellular neurofibril tangles. β-Amyloid cascade is considered the major causative player in AD. Up until now, the mechanisms underlying the process of Aβ generation and accumulation in the brain have not been well understood. Tyro3 receptor belongs to the TAM receptor subfamily of receptor protein tyrosine kinases (RPTKs. It is specifically expressed in the neurons of the neocortex and hippocampus. In this study, we established a cell model stably expressing APPswe mutants and producing Aβ. We found that overexpression of Tyro3 receptor in the cell model significantly decreased Aβ generation and also down-regulated the expression of β-site amyloid precursor protein cleaving enzyme (BACE1. However, the effects of Tyro3 were inhibited by its natural ligand, Gas6, in a concentration-dependent manner. In order to confirm the role of Tyro3 in the progression of AD development, we generated an AD transgenic mouse model accompanied by Tyro3 knockdown. We observed a significant increase in the number of amyloid plaques in the hippocampus in the mouse model. More plaque-associated clusters of astroglia were also detected. The present study may help researchers determine the role of Tyro3 receptor in the neuropathology of AD.

  13. Towards a Model of Teacher Well-Being: Personal and Job Resources Involved in Teacher Burnout and Engagement

    Science.gov (United States)

    Bermejo-Toro, Laura; Prieto-Ursúa, María; Hernández, Vicente

    2016-01-01

    Although much research has focused on the role of job demands and job resources in teacher well-being, few studies have targeted the function of personal variables. The aim of this study is to develop a comprehensive model of teacher well-being, using burnout and engagement in order to reflect, not only job demands and professional resources, but…

  14. Homology modeling of mosquito cytochrome P450 enzymes involved in pyrethroid metabolism: insights into differences in substrate selectivity

    Directory of Open Access Journals (Sweden)

    Rongnoparut Pornpimol

    2011-09-01

    Full Text Available Abstract Background Cytochrome P450 enzymes (P450s have been implicated in insecticide resistance. Anopheles minumus mosquito P450 isoforms CYP6AA3 and CYP6P7 are capable of metabolizing pyrethroid insecticides, however CYP6P8 lacks activity against this class of compounds. Findings Homology models of the three An. minimus P450 enzymes were constructed using the multiple template alignment method. The predicted enzyme model structures were compared and used for molecular docking with insecticides and compared with results of in vitro enzymatic assays. The three model structures comprise common P450 folds but differences in geometry of their active-site cavities and substrate access channels are prominent. The CYP6AA3 model has a large active site allowing it to accommodate multiple conformations of pyrethroids. The predicted CYP6P7 active site is more constrained and less accessible to binding of pyrethroids. Moreover the predicted hydrophobic interface in the active-site cavities of CYP6AA3 and CYP6P7 may contribute to their substrate selectivity. The absence of CYP6P8 activity toward pyrethroids appears to be due to its small substrate access channel and the presence of R114 and R216 that may prevent access of pyrethroids to the enzyme heme center. Conclusions Differences in active site topologies among CYPAA3, CYP6P7, and CYP6P8 enzymes may impact substrate binding and selectivity. Information obtained using homology models has the potential to enhance the understanding of pyrethroid metabolism and detoxification mediated by P450 enzymes.

  15. Assessment of University External Internships. Towards a Mixed Model for Measuring the Acquisition of Skills and the Satisfaction of Parties Involved

    OpenAIRE

    Ruiz Callado, Raúl

    2011-01-01

    The continuous improvement of management and assessment processes for curricular external internships has led a group of university teachers specialised in this area to develop a mixed model of measurement that combines the verification of skill acquisition by those students choosing external internships with the satisfaction of the parties involved in that process. They included academics, educational tutors of companies and organisations and administration and services personnel in the latt...

  16. Exact solutions to traffic density estimation problems involving the Lighthill-Whitham-Richards traffic flow model using mixed integer programming

    KAUST Repository

    Canepa, Edward S.

    2012-09-01

    This article presents a new mixed integer programming formulation of the traffic density estimation problem in highways modeled by the Lighthill Whitham Richards equation. We first present an equivalent formulation of the problem using an Hamilton-Jacobi equation. Then, using a semi-analytic formula, we show that the model constraints resulting from the Hamilton-Jacobi equation result in linear constraints, albeit with unknown integers. We then pose the problem of estimating the density at the initial time given incomplete and inaccurate traffic data as a Mixed Integer Program. We then present a numerical implementation of the method using experimental flow and probe data obtained during Mobile Century experiment. © 2012 IEEE.

  17. A hidden Markov model to identify and adjust for selection bias: an example involving mixed migration strategies

    OpenAIRE

    Fieberg, John R.; Paul B Conn

    2014-01-01

    An important assumption in observational studies is that sampled individuals are representative of some larger study population. Yet, this assumption is often unrealistic. Notable examples include online public-opinion polls, publication biases associated with statistically significant results, and in ecology, telemetry studies with significant habitat-induced probabilities of missed locations. This problem can be overcome by modeling selection probabilities simultaneously with other predicto...

  18. Errors Involved in the Taylor‘s Model for the Crustal Composition and Evolution—An Analysis of Their Causers

    Institute of Scientific and Technical Information of China (English)

    陈衍景; 秦善; 等

    1997-01-01

    It is suggested in this paper that the famous Taylor's model for the composition and evolution of the continental crust consists of three closely related key links.These links include an assumption that the surfical environment has no effect on the sedimentary REE patterns and the REE patterns in sdhales can reflect the composition of their provenance,a discovery about the discrepancy of sedimentary REE patterns between Archean and Proteroxoic,and a deduction that there was a global scale K-granitoid event at the end of the Archean.Based on a detailed discussion,this paper substantially negates the rationality of the Taylor's model and argues that its three critical links be three great errors indeed.Moreover,some other deficiencies or problems it confronts are described in this paper.The authors suggest that what led to the errors invoved in the Taylor's model is its wrongly neglecting the effect of the sedimentary envronment on the chemical composition of sediments.and that the environment should be an important factor affecting the distribution patterns of trace elements in the sediments.

  19. [Mechanisms involved in the regulation of immune response in animal model of rheumatoid arthritis in mice (CIA)].

    Science.gov (United States)

    Marcińska, Katarzyna; Szczepanik, Marian

    2010-08-04

    Rheumatoid arthritis (RA) represents an example of the autoimmune disease. With a prevalence of 1% worldwide, the pathogenesis of RA is not clear yet. At present it is thought that the pathogenesis of RA results from an inflammatory response mediated by CD4+ Th1 cells that recognize unidentified antigens present in bone joints. Recently, there is a growing evidence for a role for Th17 lymphocytes in autoimmunity, including RA, suggesting that this population of helper cells may be more important in the pathogenesis of RA than Th1 cells. Thus far, treatment modalities for RA are limited, with the prevailing one acting nonspecifically on the immune system. However, such an approach results in a general immunosuppression and is accompanied by severe side-effects. There is a large demand for developing RA therapy that particularly targets pathogenic antigen-specific T cells. Research on pathogenesis of the autoimmune diseases, and development of new drugs is now possible thanks to experimental animal models that mimic human diseases. Collagen-induced arthritis (CIA) in genetically susceptible strains of mice, rats, rabbits or rhesus monkeys has been used as an experimental model of RA, as it shares many histological and immunological features. The knowledge gained using this model allows to better understand the pathogenesis of RA and, consequently, to manipulate particular components of the immune system to develop efficient therapies.

  20. Structural model of the dimeric Parkinson’s protein LRRK2 reveals a compact architecture involving distant interdomain contacts

    Science.gov (United States)

    Guaitoli, Giambattista; Raimondi, Francesco; Gilsbach, Bernd K.; Gómez-Llorente, Yacob; Deyaert, Egon; Renzi, Fabiana; Li, Xianting; Schaffner, Adam; Jagtap, Pravin Kumar Ankush; Boldt, Karsten; von Zweydorf, Felix; Gotthardt, Katja; Lorimer, Donald D.; Yue, Zhenyu; Burgin, Alex; Janjic, Nebojsa; Sattler, Michael; Versées, Wim; Ueffing, Marius; Ubarretxena-Belandia, Iban; Kortholt, Arjan; Gloeckner, Christian Johannes

    2016-01-01

    Leucine-rich repeat kinase 2 (LRRK2) is a large, multidomain protein containing two catalytic domains: a Ras of complex proteins (Roc) G-domain and a kinase domain. Mutations associated with familial and sporadic Parkinson’s disease (PD) have been identified in both catalytic domains, as well as in several of its multiple putative regulatory domains. Several of these mutations have been linked to increased kinase activity. Despite the role of LRRK2 in the pathogenesis of PD, little is known about its overall architecture and how PD-linked mutations alter its function and enzymatic activities. Here, we have modeled the 3D structure of dimeric, full-length LRRK2 by combining domain-based homology models with multiple experimental constraints provided by chemical cross-linking combined with mass spectrometry, negative-stain EM, and small-angle X-ray scattering. Our model reveals dimeric LRRK2 has a compact overall architecture with a tight, multidomain organization. Close contacts between the N-terminal ankyrin and C-terminal WD40 domains, and their proximity—together with the LRR domain—to the kinase domain suggest an intramolecular mechanism for LRRK2 kinase activity regulation. Overall, our studies provide, to our knowledge, the first structural framework for understanding the role of the different domains of full-length LRRK2 in the pathogenesis of PD. PMID:27357661

  1. Microbial communities involved in enhanced biological phosphorus removal from wastewater--a model system in environmental biotechnology.

    Science.gov (United States)

    Nielsen, Per Halkjær; Saunders, Aaron Marc; Hansen, Aviaja Anna; Larsen, Poul; Nielsen, Jeppe Lund

    2012-06-01

    Enhanced biological phosphorus removal (EBPR) is one of the most advanced and complicated wastewater treatment processes applied today, and it is becoming increasingly popular worldwide as a sustainable way to remove and potentially reuse P. It is carried out by complex microbial communities consisting primarily of uncultured microorganisms. The EBPR process is a well-studied system with clearly defined boundaries which makes it very suitable as a model ecosystem in microbial ecology. Of particular importance are the transformations of C, N, and P, the solid-liquid separation properties and the functional and structural stability. A range of modern molecular methods has been used to study these communities in great detail including single cell microbiology, various -omics methods, flux analyses, and modeling making this one of the best studied microbial ecosystems so far. Recently, an EBPR core microbiome has been described and we present in this article some highlights and show how this complex microbial community can be used as model ecosystem in environmental biotechnology.

  2. A cellular model of memory reconsolidation involves reactivation-induced destabilization and restabilization at the sensorimotor synapse in Aplysia.

    Science.gov (United States)

    Lee, Sue-Hyun; Kwak, Chuljung; Shim, Jaehoon; Kim, Jung-Eun; Choi, Sun-Lim; Kim, Hyoung F; Jang, Deok-Jin; Lee, Jin-A; Lee, Kyungmin; Lee, Chi-Hoon; Lee, Young-Don; Miniaci, Maria Concetta; Bailey, Craig H; Kandel, Eric R; Kaang, Bong-Kiun

    2012-08-28

    The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval and needs to be reconsolidated before it can be stabilized. However, it is unclear from earlier studies whether the same synapses involved in encoding the memory trace are those that are destabilized and restabilized after the synaptic reactivation that accompanies memory retrieval, or whether new and different synapses are recruited. To address this issue, we studied a simple nonassociative form of memory, long-term sensitization of the gill- and siphon-withdrawal reflex in Aplysia, and its cellular analog, long-term facilitation at the sensory-to-motor neuron synapse. We found that after memory retrieval, behavioral long-term sensitization in Aplysia becomes labile via ubiquitin/proteasome-dependent protein degradation and is reconsolidated by means of de novo protein synthesis. In parallel, we found that on the cellular level, long-term facilitation at the sensory-to-motor neuron synapse that mediates long-term sensitization is also destabilized by protein degradation and is restabilized by protein synthesis after synaptic reactivation, a procedure that parallels memory retrieval or retraining evident on the behavioral level. These results provide direct evidence that the same synapses that store the long-term memory trace encoded by changes in the strength of synaptic connections critical for sensitization are disrupted and reconstructed after signal retrieval.

  3. Lung endothelial barrier protection by iloprost in the two-hit models of VILI involves inhibition of Rho signaling

    Science.gov (United States)

    Birukova, Anna A.; Fu, Panfeng; Xing, Junjie; Cokic, Ivan; Birukov, Konstantin G.

    2010-01-01

    Mechanical ventilation at high tidal volume may cause pulmonary capillary leakage and acute lung inflammation culminating in ventilator-induced lung injury. Iloprost is a stable synthetic analogue of prostaglandin I2 used for treatment of pulmonary hypertension, which also showed endothelium-dependent anti-edemagenic effects in the models of lung injury. To test the hypothesis that iloprost may attenuate lung inflammation and lung endothelial barrier disruption caused by pathologic lung distension and coagulation system component thrombin, we used cell and animal two-hit models of ventilator-induced lung injury. Mice received triple injection of iloprost (2 μg/kg, intravenous instillation) at 0, 40 and 80 min after onset of high tidal volume (HTV) mechanical ventilation (30 ml/kg, 4 hrs) combined with administration of thrombin receptor activating peptide 6 (TRAP6, 3 × 10−7 mol/mouse, intratracheal instillation). After 4 hrs of ventilation, bronchoalveolar lavage (BAL), histological analysis, and measurements of Evans blue accumulation in the lung tissue lung were performed. Effects of iloprost on endothelial barrier dysfunction were further assessed in pulmonary endothelial cells (EC) exposed to thrombin and pathologic (18%) cyclic stretch. Combination of HTV and TRAP6 enhanced accumulation of neutrophils in BAL fluid and lung parenchyma, increased BAL protein content and endothelial permeability judged by Evans blue extravasation in the lung tissue. These effects were markedly attenuated by iloprost. Application of 18% cyclic stretch to pulmonary EC enhanced thrombin-induced EC paracellular gap formation and Rho-GTPase-mediated phosphorylation of regulatory myosin light chains and myosin phosphatase. Iloprost markedly inhibited Rho-kinase mediated site-specific phosphorylation of myosin phosphatase, and prevented cyclic stretch- and thrombin-induced endothelial monolayer disruption. This study characterizes for the first time the protective effects of

  4. Antinociceptive Effect of Ghrelin in a Rat Model of Irritable Bowel Syndrome Involves TRPV1/Opioid Systems

    Directory of Open Access Journals (Sweden)

    Yuqing Mao

    2017-09-01

    Full Text Available Background/Aims: Irritable bowel syndrome (IBS, defined as recurrent abdominal pain and changes in bowel habits, seriously affects quality of life and ability to work. Ghrelin is a brain-gut hormone, which has been reported to show antinociceptive effects in peripheral pain. We investigated the effect of ghrelin on visceral hypersensitivity and pain in a rat model of IBS. Methods: Maternal deprivation (MD was used to provide a stress-induced model of IBS in Wistar rats. Colorectal distension (CRD was used to detect visceral sensitivity, which was evaluated by abdominal withdrawal reflex (AWR scores. Rats that were confirmed to have visceral hypersensitivity after MD were injected with ghrelin (10 µg/kg subcutaneously twice a week from weeks 7 to 8. [D-Lys3]-GHRP-6 (100 nmol/L and naloxone (100 nmol/L were administered subcutaneously to block growth hormone secretagogue receptor 1α (GHS-R1α and opioid receptors, respectively. Expression of transient receptor potential vanilloid type 1 (TRPV1 and µ and κ opioid receptors (MOR and KOR in colon, dorsal root ganglion (DRG and cerebral cortex tissues were detected by western blotting, quantitative real-time polymerase chain reaction (qRT-PCR, immunohistochemical analyses and immunofluorescence. Results: Ghrelin treatment increased expression of opioid receptors and inhibited expression of TRPV1 in colon, dorsal root ganglion (DRG and cerebral cortex. The antinociceptive effect of ghrelin in the rat model of IBS was partly blocked by both the ghrelin antagonist [D-Lys3]-GHRP-6 and the opioid receptor antagonist naloxone. Conclusion: The results indicate that ghrelin exerted an antinociceptive effect, which was mediated via TRPV1/opioid systems, in IBS-induced visceral hypersensitivity. Ghrelin might potentially be used as a new treatment for IBS.

  5. Murine neural stem cells model Hunter disease in vitro: glial cell-mediated neurodegeneration as a possible mechanism involved.

    Science.gov (United States)

    Fusar Poli, E; Zalfa, C; D'Avanzo, F; Tomanin, R; Carlessi, L; Bossi, M; Nodari, L Rota; Binda, E; Marmiroli, P; Scarpa, M; Delia, D; Vescovi, A L; De Filippis, L

    2013-11-07

    Mucopolysaccharidosis type II (MPSII or Hunter Syndrome) is a lysosomal storage disorder caused by the deficit of iduronate 2-sulfatase (IDS) activity and characterized by progressive systemic and neurological impairment. As the early mechanisms leading to neuronal degeneration remain elusive, we chose to examine the properties of neural stem cells (NSCs) isolated from an animal model of the disease in order to evaluate whether their neurogenic potential could be used to recapitulate the early phases of neurogenesis in the brain of Hunter disease patients. Experiments here reported show that NSCs derived from the subventricular zone (SVZ) of early symptomatic IDS-knockout (IDS-ko) mouse retained self-renewal capacity in vitro, but differentiated earlier than wild-type (wt) cells, displaying an evident lysosomal aggregation in oligodendroglial and astroglial cells. Consistently, the SVZ of IDS-ko mice appeared similar to the wt SVZ, whereas the cortex and striatum presented a disorganized neuronal pattern together with a significant increase of glial apoptotic cells, suggesting that glial degeneration likely precedes neuronal demise. Interestingly, a very similar pattern was observed in the brain cortex of a Hunter patient. These observations both in vitro, in our model, and in vivo suggest that IDS deficit seems to affect the late phases of neurogenesis and/or the survival of mature cells rather than NSC self-renewal. In particular, platelet-derived growth factor receptor-α-positive (PDGFR-α+) glial progenitors appeared reduced in both the IDS-ko NSCs and in the IDS-ko mouse and human Hunter brains, compared with the respective healthy controls. Treatment of mutant NSCs with IDS or PDGF throughout differentiation was able to increase the number of PDGFR-α+ cells and to reduce that of apoptotic cells to levels comparable to wt. This evidence supports IDS-ko NSCs as a reliable in vitro model of the disease, and suggests the rescue of PDGFR-α+ glial cells as a

  6. Beyond the MHC: A canine model of dermatomyositis shows a complex pattern of genetic risk involving novel loci

    Science.gov (United States)

    Evans, Jacquelyn M.; Hill, Cody M.; Anderson, Kendall J.

    2017-01-01

    Juvenile dermatomyositis (JDM) is a chronic inflammatory myopathy and vasculopathy driven by genetic and environmental influences. Here, we investigated the genetic underpinnings of an analogous, spontaneous disease of dogs also termed dermatomyositis (DMS). As in JDM, we observed a significant association with a haplotype of the major histocompatibility complex (MHC) (DLA-DRB1*002:01/-DQA1*009:01/-DQB1*001:01), particularly in homozygosity (P-val = 0.0001). However, the high incidence of the haplotype among healthy dogs indicated that additional genetic risk factors are likely involved in disease progression. We conducted genome-wide association studies in two modern breeds having common ancestry and detected strong associations with novel loci on canine chromosomes 10 (P-val = 2.3X10-12) and 31 (P-val = 3.95X10-8). Through whole genome resequencing, we identified primary candidate polymorphisms in conserved regions of PAN2 (encoding p.Arg492Cys) and MAP3K7CL (c.383_392ACTCCACAAA>GACT) on chromosomes 10 and 31, respectively. Analyses of these polymorphisms and the MHC haplotypes revealed that nine of 27 genotypic combinations confer high or moderate probability of disease and explain 93% of cases studied. The pattern of disease risk across PAN2 and MAP3K7CL genotypes provided clear evidence for a significant epistatic foundation for this disease, a risk further impacted by MHC haplotypes. We also observed a genotype-phenotype correlation wherein an earlier age of onset is correlated with an increased number of risk alleles at PAN2 and MAP3K7CL. High frequencies of multiple genetic risk factors are unique to affected breeds and likely arose coincident with artificial selection for desirable phenotypes. Described herein is the first three-locus association with a complex canine disease and two novel loci that provide targets for exploration in JDM and related immunological dysfunction. PMID:28158183

  7. Hairless expression attenuates apoptosis in a mouse model and the COS cell line; involvement of p53.

    Directory of Open Access Journals (Sweden)

    Cliona O'Driscoll

    Full Text Available BACKGROUND: Neurons are more likely to die through apoptosis in the immature brain after injury whereas adult neurons in the mature brain die by necrosis. Several studies have suggested that this maturational change in the mechanism of cell death is regulated, in part, by thyroid hormone. We examined the involvement of the hairless (Hr gene which has been suspected of having a role in cell cycle regulation and apoptosis in the hair follicle and is strongly regulated by the thyroid hormone in the brain. METHODOLOGY: Forced expression of Hr by transfection decreased the number of apoptotic nuclei, levels of caspase-3 activity, and cytosolic cytochrome C in COS cells exposed to staurosporine and tunicamycin. Similarly, caspase-3 activity was lower and the decrease in mitochondrial membrane potential was smaller in cultures of adult cerebellar granule neurons from wild type mice compared to Hr knockout mice induced to undergo apoptosis. In vivo, apoptosis as detected by positive TUNEL labeling and caspase 3 activity was lower in wild-type mice compared to Hr knockouts after exposure to trimethyltin. Hr expression lowered levels of p53, p53 mediated reporter gene activity, and lower levels of the pro-apoptotic Bcl2 family member Bax in COS cells. Finally, Hr expression did not attenuate apoptosis in mouse embryonic fibroblasts from p53 knockout mice but was effective in mouse embryonic fibroblasts from wild type mice. CONCLUSIONS/SIGNIFICANCE: Overall, our studies demonstrate that Hr evokes an anti-apoptotic response by repressing expression of p53 and pro-apoptotic events regulated by p53.

  8. A novel orally available inhibitor of focal adhesion signaling increases survival in a xenograft model of diffuse large B-cell lymphoma with central nervous system involvement.

    Science.gov (United States)

    Bosch, Rosa; Moreno, María José; Dieguez-Gonzalez, Rebeca; Céspedes, María Virtudes; Gallardo, Alberto; Trias, Manuel; Grañena, Albert; Sierra, Jorge; Casanova, Isolda; Mangues, Ramon

    2013-08-01

    Central nervous system dissemination is a relatively uncommon but almost always fatal complication in diffuse large B-cell lymphoma patients. Optimal therapy for central nervous involvement in this malignancy has not been established. In this paper, we aimed to evaluate the therapeutic effect of E7123, a celecoxib derivative that inhibits focal adhesion signaling, in a novel xenograft model of diffuse large B-cell lymphoma with central nervous system involvement. Cells obtained after disaggregation of HT subcutaneous tumors (HT-SC cells) were intravenously injected in NOD/SCID mice. These mice received oral vehicle or 75 mg/kg of E7123 daily until they were euthanized for weight loss or signs of sickness. The antitumor effect of E7123 was validated in an independent experiment using a bioluminescent mouse model. Intravenously injected HT-SC cells showed higher take rate and higher central nervous system tropism (associated with increased expression of β1-integrin and p130Cas proteins) than HT cells. The oral administration of E7123 significantly increased survival time in 2 independent experiments using mice injected with unmodified or bioluminescent HT-SC cells. We have developed a new xenograft model of diffuse large B-cell lymphoma with central nervous system involvement that can be used in the pre-clinical evaluation of new drugs for this malignancy. E7123 is a new, well-tolerated and orally available therapeutic agent that merits further investigation since it may improve current management of diffuse large B-cell lymphoma patients with central nervous system involvement.

  9. Modeling of Glycerol-3-Phosphate Transporter Suggests a Potential ‘Tilt’ Mechanism involved in its Function

    Science.gov (United States)

    Tsigelny, Igor F.; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K.

    2009-01-01

    Many major facilitator superfamily (MFS) transporters have similar 12-transmembrane α-helical topologies with two six-helix halves connected by a long loop. In humans, these transporters participate in key physiological processes and are also, as in the case of members of the organic anion transporter (OAT) family, of pharmaceutical interest. Recently, crystal structures of two bacterial representatives of the MFS family — the glycerol-3-phosphate transporter (GlpT) and lac-permease (LacY) — have been solved and, because of assumptions regarding the high structural conservation of this family, there is hope that the results can be applied to mammalian transporters as well. Based on crystallography, it has been suggested that a major conformational “switching” mechanism accounts for ligand transport by MFS proteins. This conformational switch would then allow periodic changes in the overall transporter configuration, resulting in its cyclic opening to the periplasm or cytoplasm. Following this lead, we have modeled a possible “switch” mechanism in GlpT, using the concept of rotation of protein domains as in the DynDom program17 and membranephilic constraints predicted by the MAPAS program.23 We found that the minima of energies of intersubunit interactions support two alternate positions consistent with their transport properties. Thus, for GlpT, a “tilt” of 9°–10° rotation had the most favorable energetics of electrostatic interaction between the two halves of the transporter; moreover, this confirmation was sufficient to suggest transport of the ligand across the membrane. We conducted steered molecular dynamics simulations of the GlpT-ligand system to explore how glycerol-3-phosphate would be handled by the “tilted” structure, and obtained results generally consistent with experimental mutagenesis data. While biochemical data remain most consistent with a single-site alternating access model, our results raise the possibility that, while

  10. Genes involved in thoracic exoskeleton formation during the pupal-to-adult molt in a social insect model, Apis mellifera.

    Science.gov (United States)

    Soares, Michelle Prioli Miranda; Barchuk, Angel Roberto; Simões, Ana Carolina Quirino; Dos Santos Cristino, Alexandre; de Paula Freitas, Flávia Cristina; Canhos, Luísa Lange; Bitondi, Márcia Maria Gentile

    2013-08-28

    The insect exoskeleton provides shape, waterproofing, and locomotion via attached somatic muscles. The exoskeleton is renewed during molting, a process regulated by ecdysteroid hormones. The holometabolous pupa transforms into an adult during the imaginal molt, when the epidermis synthe3sizes the definitive exoskeleton that then differentiates progressively. An important issue in insect development concerns how the exoskeletal regions are constructed to provide their morphological, physiological and mechanical functions. We used whole-genome oligonucleotide microarrays to screen for genes involved in exoskeletal formation in the honeybee thoracic dorsum. Our analysis included three sampling times during the pupal-to-adult molt, i.e., before, during and after the ecdysteroid-induced apolysis that triggers synthesis of the adult exoskeleton. Gene ontology annotation based on orthologous relationships with Drosophila melanogaster genes placed the honeybee differentially expressed genes (DEGs) into distinct categories of Biological Process and Molecular Function, depending on developmental time, revealing the functional elements required for adult exoskeleton formation. Of the 1,253 unique DEGs, 547 were upregulated in the thoracic dorsum after apolysis, suggesting induction by the ecdysteroid pulse. The upregulated gene set included 20 of the 47 cuticular protein (CP) genes that were previously identified in the honeybee genome, and three novel putative CP genes that do not belong to a known CP family. In situ hybridization showed that two of the novel genes were abundantly expressed in the epidermis during adult exoskeleton formation, strongly implicating them as genuine CP genes. Conserved sequence motifs identified the CP genes as members of the CPR, Tweedle, Apidermin, CPF, CPLCP1 and Analogous-to-Peritrophins families. Furthermore, 28 of the 36 muscle-related DEGs were upregulated during the de novo formation of striated fibers attached to the exoskeleton. A

  11. An analysis of two-body non-leptonic B decays involving light mesons in the standard model

    CERN Document Server

    Ali, A

    1998-01-01

    We report a theoretical analysis of the exclusive non-leptonic decays of B mesons into two light mesons, some of which have been measured recently by the CLEO collaboration. Our analysis is carried out in the context of an effective Hamiltonian based on the Standard Model (SM), using next-to-leading order perturbative QCD calculations. Using a factorization ansatz for the hadronic matrix elements, we show that existing data are accounted for in this approach. Thus, theoretical scenarios with a substantially enhanced Wilson coefficient of the chromomagnetic dipole operator (as compared to the SM) and/or those with a substantial color-singlet $c\\bar{c}$ component in the wave function of rates, the branching ratios for the decays $B^0 (\\bar{B^0}) \\to \\pi^\\pm experimental limits. Implications of some of these measurements for the parameters of the CKM matrix are presented.

  12. The cell recognition model in chlorolichens involving a fungal lectin binding to an algal ligand can be extended to cyanolichens.

    Science.gov (United States)

    Vivas, M; Sacristán, M; Legaz, M E; Vicente, C

    2010-07-01

    Leptogium corniculatum, a cyanolichen containing Nostoc as photobiont, produces and secretes arginase to culture medium containing arginine. This secreted arginase was pre-purified by affinity chromatography on beads of activated agarose to which a polygalactosylated urease, purified from Evernia prunastri, was attached. Arginase was eluted from the beads with 50 mm alpha-d-galactose. The eluted arginase binds preferentially to the cell surface of Nostoc isolated from this lichen thallus, although it is also able to bind, to some extent, to the cell surface of the chlorobiont isolated from E. prunastri. Previous studies in chlorolichens have shown that a fungal lectin that develops subsidiary arginase activity can be a factor in recognition of compatible algal cells through binding to a polygalactosylated urease, which acts as a lectin ligand in the algal cell wall. Our experiments demonstrate that this model can now be extended to cyanolichens.

  13. Molecular phylogenetics and comparative modeling of HEN1, a methyltransferase involved in plant microRNA biogenesis

    Directory of Open Access Journals (Sweden)

    Obarska Agnieszka

    2006-01-01

    Full Text Available Abstract Background Recently, HEN1 protein from Arabidopsis thaliana was discovered as an essential enzyme in plant microRNA (miRNA biogenesis. HEN1 transfers a methyl group from S-adenosylmethionine to the 2'-OH or 3'-OH group of the last nucleotide of miRNA/miRNA* duplexes produced by the nuclease Dicer. Previously it was found that HEN1 possesses a Rossmann-fold methyltransferase (RFM domain and a long N-terminal extension including a putative double-stranded RNA-binding motif (DSRM. However, little is known about the details of the structure and the mechanism of action of this enzyme, and about its phylogenetic origin. Results Extensive database searches were carried out to identify orthologs and close paralogs of HEN1. Based on the multiple sequence alignment a phylogenetic tree of the HEN1 family was constructed. The fold-recognition approach was used to identify related methyltransferases with experimentally solved structures and to guide the homology modeling of the HEN1 catalytic domain. Additionally, we identified a La-like predicted RNA binding domain located C-terminally to the DSRM domain and a domain with a peptide prolyl cis/trans isomerase (PPIase fold, but without the conserved PPIase active site, located N-terminally to the catalytic domain. Conclusion The bioinformatics analysis revealed that the catalytic domain of HEN1 is not closely related to any known RNA:2'-OH methyltransferases (e.g. to the RrmJ/fibrillarin superfamily, but rather to small-molecule methyltransferases. The structural model was used as a platform to identify the putative active site and substrate-binding residues of HEN and to propose its mechanism of action.

  14. Application of a random effects negative binomial model to examine tram-involved crash frequency on route sections in Melbourne, Australia.

    Science.gov (United States)

    Naznin, Farhana; Currie, Graham; Logan, David; Sarvi, Majid

    2016-07-01

    Safety is a key concern in the design, operation and development of light rail systems including trams or streetcars as they impose crash risks on road users in terms of crash frequency and severity. The aim of this study is to identify key traffic, transit and route factors that influence tram-involved crash frequencies along tram route sections in Melbourne. A random effects negative binomial (RENB) regression model was developed to analyze crash frequency data obtained from Yarra Trams, the tram operator in Melbourne. The RENB modelling approach can account for spatial and temporal variations within observation groups in panel count data structures by assuming that group specific effects are randomly distributed across locations. The results identify many significant factors effecting tram-involved crash frequency including tram service frequency (2.71), tram stop spacing (-0.42), tram route section length (0.31), tram signal priority (-0.25), general traffic volume (0.18), tram lane priority (-0.15) and ratio of platform tram stops (-0.09). Findings provide useful insights on route section level tram-involved crashes in an urban tram or streetcar operating environment. The method described represents a useful planning tool for transit agencies hoping to improve safety performance.

  15. Anti-inflammatory effect of simvastatin in an experimental model of spinal cord trauma: involvement of PPAR-α

    Directory of Open Access Journals (Sweden)

    Esposito Emanuela

    2012-04-01

    Full Text Available Abstract Background Statins such as simvastatin are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA reductase used in the prevention of cardiovascular disease. In addition to their cholesterol-lowering activities, statins exert pleiotropic anti-inflammatory effects, which might contribute to their beneficial effects on lipid-unrelated inflammatory diseases. Recently it has been demonstrated that the peroxisome proliferator-activated receptor (PPAR-α mediates anti-inflammatory effects of simvastatin in vivo models of acute inflammation. Moreover, previous results suggest that PPAR-α plays a role in control of secondary inflammatory process associated with spinal cord injury (SCI. Methods With the aim to characterize the role of PPAR-α in simvastatin activity, we tested the efficacy of simvastatin (10 mg/kg dissolved in saline i.p. 1 h and 6 h after the trauma in an experimental model of SCI induced in mice by extradural compression of the spinal cord (T6-T7 level using an aneurysm clip with a closing force of 24 g via a four-level T5-T8 laminectomy, and comparing mice lacking PPAR-α (PPAR-α KO with wild type (WT mice. In order to elucidate whether the effects of simvastatin are due to activation of the PPAR-α, we also investigated the effect of a PPAR-α antagonist, GW6471 (1 mg/kg administered i.p. 30 min prior treatment with simvastatin on the protective effects of on simvastatin. Results Results indicate that simvastatin activity is weakened in PPAR-α KO mice, as compared to WT controls. In particular, simvastatin was less effective in PPAR-α KO, compared to WT mice, as evaluated by inhibition of the degree of spinal cord inflammation, neutrophil infiltration, nitrotyrosine formation, pro-inflammmatory cytokine expression, nuclear factor (NF-κB activation, inducible nitric-oxide synthase (iNOS expression, and apoptosis. In addition we demonstrated that GW6471 significantly antagonized the effect of the statin and thus

  16. Finding biomarkers in non-model species: literature mining of transcription factors involved in bovine embryo development

    Directory of Open Access Journals (Sweden)

    Turenne Nicolas

    2012-08-01

    Full Text Available Abstract Background Since processes in well-known model organisms have specific features different from those in Bos taurus, the organism under study, a good way to describe gene regulation in ruminant embryos would be a species-specific consideration of closely related species to cattle, sheep and pig. However, as highlighted by a recent report, gene dictionaries in pig are smaller than in cattle, bringing a risk to reduce the gene resources to be mined (and so for sheep dictionaries. Bioinformatics approaches that allow an integration of available information on gene function in model organisms, taking into account their specificity, are thus needed. Besides these closely related and biologically relevant species, there is indeed much more knowledge of (i trophoblast proliferation and differentiation or (ii embryogenesis in human and mouse species, which provides opportunities for reconstructing proliferation and/or differentiation processes in other mammalian embryos, including ruminants. The necessary knowledge can be obtained partly from (i stem cell or cancer research to supply useful information on molecular agents or molecular interactions at work in cell proliferation and (ii mouse embryogenesis to supply useful information on embryo differentiation. However, the total number of publications for all these topics and species is great and their manual processing would be tedious and time consuming. This is why we used text mining for automated text analysis and automated knowledge extraction. To evaluate the quality of this “mining”, we took advantage of studies that reported gene expression profiles during the elongation of bovine embryos and defined a list of transcription factors (or TF, n = 64 that we used as biological “gold standard”. When successful, the “mining” approach would identify them all, as well as novel ones. Methods To gain knowledge on molecular-genetic regulations in a non model organism, we offer an

  17. Phenylpyrazole insecticides induce cytotoxicity by altering mechanisms involved in cellular energy supply in the human epithelial cell model Caco-2.

    Science.gov (United States)

    Vidau, Cyril; Brunet, Jean-Luc; Badiou, Alexandra; Belzunces, Luc P

    2009-06-01

    Phenylpyrazoles are relatively new insecticides designed to manage problematic insect resistance and public health hazards encountered with older pesticide families. In vitro cytotoxicity induced by the phenylpyrazole insecticides, Ethiprol and Fipronil, and Fipronil metabolites, sulfone and sulfide, was studied in Caco-2 cells. This cellular model was chosen because it made possible to mimic the primary site of oral exposure to xenobiotics, the intestinal epithelium. Assessment of the barrier function of Caco-2 epithelium was assessed by TEER measurement and showed a major loss of barrier integrity after exposure to Fipronil and its metabolites, but not to Ethiprol. The disruption of the epithelial barrier was attributed to severe ATP depletion independent of cell viability, as revealed by LDH release. The origin of energetic metabolism failure was investigated and revealed a transient enhancement of tetrazolium salt reduction and an increase in lactate production by Caco-2 cells, suggesting an increase in glucose metabolism by pesticides. Cellular symptoms observed in these experiments lead us to hypothesize that phenylpyrazole insecticides interacted with mitochondria.

  18. Damage of polyesters by the atmospheric free radical oxidant NO3•: a product study involving model systems

    Directory of Open Access Journals (Sweden)

    Catrin Goeschen

    2013-09-01

    Full Text Available Manufactured polymer materials are used in increasingly demanding applications, but their lifetime is strongly influenced by environmental conditions. In particular, weathering and ageing leads to dramatic changes in the properties of the polymers, which results in decreased service life and limited usage. Despite the heavy reliance of our society on polymers, the mechanism of their degradation upon exposure to environmental oxidants is barely understood. In this work, model systems of important structural motifs in commercial high-performing polyesters were used to study the reaction with the night-time free radical oxidant NO3• in the absence and presence of other radical and non-radical oxidants. Identification of the products revealed ‘hot spots’ in polyesters that are particularly vulnerable to attack by NO3• and insight into the mechanism of oxidative damage by this environmentally important radical. It is suggested that both intermediates as well as products of these reactions are potentially capable of promoting further degradation processes in polyesters under environmental conditions.

  19. Damage of polyesters by the atmospheric free radical oxidant NO3 (•): a product study involving model systems.

    Science.gov (United States)

    Goeschen, Catrin; Wille, Uta

    2013-01-01

    Manufactured polymer materials are used in increasingly demanding applications, but their lifetime is strongly influenced by environmental conditions. In particular, weathering and ageing leads to dramatic changes in the properties of the polymers, which results in decreased service life and limited usage. Despite the heavy reliance of our society on polymers, the mechanism of their degradation upon exposure to environmental oxidants is barely understood. In this work, model systems of important structural motifs in commercial high-performing polyesters were used to study the reaction with the night-time free radical oxidant NO3 (•) in the absence and presence of other radical and non-radical oxidants. Identification of the products revealed 'hot spots' in polyesters that are particularly vulnerable to attack by NO3 (•) and insight into the mechanism of oxidative damage by this environmentally important radical. It is suggested that both intermediates as well as products of these reactions are potentially capable of promoting further degradation processes in polyesters under environmental conditions.

  20. Anti-Inflammatory Effect of Emblica officinalis in Rodent Models of Acute and Chronic Inflammation: Involvement of Possible Mechanisms

    Directory of Open Access Journals (Sweden)

    Mahaveer Golechha

    2014-01-01

    Full Text Available Emblica officinalis, commonly known as amla in Ayurveda, is unarguably the most important medicinal plant for prevention and treatment of various ailments. The present study investigated the anti-inflammatory activity of hydroalcoholic extract of Emblica officinalis (HAEEO. Acute inflammation in rats was induced by the subplantar injection of carrageenan, histamine, serotonin, and prostaglandin E2 and chronic inflammation was induced by the cotton pellet granuloma. Intraperitoneal (i.p. administration of HAEEO at all the tested doses (300, 500, and 700 mg/kg significantly (P<0.001 inhibited rat paw edema against all phlogistic agents and also reduced granuloma formation. However, at the dose of 700 mg/kg, HAEEO exhibited maximum anti-inflammatory activity in all experimental models, and the effects were comparable to that of the standard anti-inflammatory drugs. Additionally, in paw tissue the antioxidant activity of HAEEO was also measured and it was found that HAEEO significantly (P<0.001 increased glutathione, superoxide dismutase, and catalase activity and subsequently reduced lipid peroxidation evidenced by reduced malondialdehyde. Taken all together, the results indicated that HAEEO possessed potent anti-inflammatory activity and it may hold therapeutic promise in the management of acute and chronic inflammatory conditions.

  1. Uric Acid Amplifies Aβ Amyloid Effects Involved in the Cognitive Dysfunction/Dementia: Evidences From an Experimental Model In Vitro.

    Science.gov (United States)

    Desideri, Giovambattista; Gentile, Roberta; Antonosante, Andrea; Benedetti, Elisabetta; Grassi, Davide; Cristiano, Loredana; Manocchio, Antonello; Selli, Sara; Ippoliti, Rodolfo; Ferri, Claudio; Borghi, Claudio; Giordano, Antonio; Cimini, Annamaria

    2017-05-01

    There is still a considerable debate concerning whether uric acid is neuroprotective or neurotoxic agent. To clarify this topic, we tested the effects of uric acid on neuronal cells biology by using differentiated SHSY5Y neuroblastoma cells incubated with amyloid β to reproduce an in vitro model of Alzheimer's disease. The incubation of cells with uric acid at the dose of 40 µM or higher significantly reduced cell viability and potentiated the proapoptotic effect of amyloid β. Finally, uric acid enhanced the generation of 4-hydroxynonenal and the expression of PPARβ/δ promoted by amyloid β, indicating a prooxidant effects. In conclusion, uric acid could exert a detrimental influence on neuronal biology being this influence further potentiated by the concomitant exposure to neurotoxic stimuli. This effect is evident for uric acid concentrations close to those achievable in cerebrospinal fluid in presence of mild hyperuricemia thus suggesting a potential role of uric acid in pathophysiology of cognitive dysfunction. These effects are influenced by the concentrations of uric acid and by the presence of favoring conditions that commonly occur in neurodegenerative disorders and well as in the aging brain, including increased oxidative stress and exposure to amyloid β. J. Cell. Physiol. 232: 1069-1078, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Riluzole neuroprotection in a parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation

    Directory of Open Access Journals (Sweden)

    Carbone Marica

    2012-04-01

    Full Text Available Abstract Background Riluzole is a neuroprotective drug used in the treatment of motor neurone disease. Recent evidence suggests that riluzole can up-regulate the expression and activity of the astrocyte glutamate transporter, GLT-1. Given that regulation of glutamate transport is predicted to be neuroprotective in Parkinson's disease, we tested the effect of riluzole in parkinsonian rats which had received a unilateral 6-hydroxydopamine injection into the median forebrain bundle. Results Rats were treated with intraperitoneal riluzole (4 mg/kg or 8 mg/kg, 1 hour before the lesion then once daily for seven days. Riluzole produced a modest but significant attenuation of dopamine neurone degeneration, assessed by suppression of amphetamine-induced rotations, preservation of tyrosine hydroxylase positive neuronal cell bodies in the substantia nigra pars compacta and attenuation of striatal tyrosine hydroxylase protein loss. Seven days after 6-hydroxydopamine lesion, reactive astrocytosis was observed in the striatum, as determined by increases in expression of glial fibrillary acidic protein, however the glutamate transporter, GLT-1, which is also expressed in astrocytes was not regulated by the lesion. Conclusions The results confirm that riluzole is a neuroprotective agent in a rodent model of parkinson's disease. Riluzole administration did not regulate GLT-1 levels but significantly reduced GFAP levels, in the lesioned striatum. Riluzole suppression of reactive astrocytosis is an intriguing finding which might contribute to the neuroprotective effects of this drug.

  3. Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression

    KAUST Repository

    Meylan, E M

    2016-07-12

    Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1−/− mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1−/− mice. Quantitative polymerase chain reaction and western blot analyses confirmed Agmat upregulation in the Crtc1−/− prefrontal cortex (PFC) and hippocampus, which were further demonstrated by confocal immunofluorescence microscopy to comprise an increased number of Agmat-expressing cells, notably parvalbumin- and somatostatin-positive interneurons. Acute agmatine and ketamine treatments comparably improved the depressive-like behavior of male and female Crtc1−/− mice in the forced swim test, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit because of upregulated Agmat. Agmatine rapidly increased brain-derived neurotrophic factor (BDNF) levels only in the PFC of wild-type (WT) females, and decreased eukaryotic elongation factor 2 (eEF2) phosphorylation in the PFC of male and female WT mice, indicating that agmatine might be a fast-acting antidepressant with N-methyl-D-aspartate (NMDA) receptor antagonist properties. Collectively, these findings implicate Agmat in the depressive-like phenotype of Crtc1−/− mice, refine current understanding of the agmatinergic system in the brain and highlight its putative role in major depression.

  4. Disruption of social cognition in the sub-chronic PCP rat model of schizophrenia: Possible involvement of the endocannabinoid system.

    Science.gov (United States)

    Seillier, Alexandre; Giuffrida, Andrea

    2016-02-01

    Previous studies have shown that social withdrawal in the phencyclidine (PCP) rat model of schizophrenia results from deficient endocannabinoid-induced activation of CB1 receptors. To understand the underlying cognitive mechanisms of the social deficit in PCP-treated rats, we examined the impact of pharmacological manipulation of the endocannabinoid system on sociability (i.e. social approach) and social novelty preference (which relies on social recognition). Control rats showed a clear preference for a "social" cage (i.e. unfamiliar stimulus rat placed under a wire mesh cage) versus an "empty" cage, and spent more time exploring a "novel" cage (i.e. new stimulus rat) versus a "familiar" cage. In contrast, rats receiving PCP (5 mg/kg, b.i.d. for 7 days, followed by a 7 day-washout period) showed intact sociability, but lacked social novelty preference. This PCP-induced deficit was due to increased activity at CB1 receptors as it was reversed by systemic administration of the CB1 antagonist AM251 (1 mg/kg). In agreement with this hypothesis, the cannabinoid agonist CP55,940 (0.003-0.03 mg/kg) dose-dependently suppressed social novelty preference in control animals without affecting sociability. Taken together, these data suggest that PCP-treated rats have a deficit in social cognition, possibly induced by increased stimulation of CB1 receptors. This deficit, however, is distinct from the social withdrawal previously observed in these animals, as the latter is due to deficient, rather than increased, CB1 stimulation. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  5. Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression.

    Science.gov (United States)

    Meylan, E M; Breuillaud, L; Seredenina, T; Magistretti, P J; Halfon, O; Luthi-Carter, R; Cardinaux, J-R

    2016-07-12

    Recent studies implicate the arginine-decarboxylation product agmatine in mood regulation. Agmatine has antidepressant properties in rodent models of depression, and agmatinase (Agmat), the agmatine-degrading enzyme, is upregulated in the brains of mood disorder patients. We have previously shown that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) associate behavioral and molecular depressive-like endophenotypes, as well as blunted responses to classical antidepressants. Here, the molecular basis of the behavioral phenotype of Crtc1(-/-) mice was further examined using microarray gene expression profiling that revealed an upregulation of Agmat in the cortex of Crtc1(-/-) mice. Quantitative polymerase chain reaction and western blot analyses confirmed Agmat upregulation in the Crtc1(-/-) prefrontal cortex (PFC) and hippocampus, which were further demonstrated by confocal immunofluorescence microscopy to comprise an increased number of Agmat-expressing cells, notably parvalbumin- and somatostatin-positive interneurons. Acute agmatine and ketamine treatments comparably improved the depressive-like behavior of male and female Crtc1(-/-) mice in the forced swim test, suggesting that exogenous agmatine has a rapid antidepressant effect through the compensation of agmatine deficit because of upregulated Agmat. Agmatine rapidly increased brain-derived neurotrophic factor (BDNF) levels only in the PFC of wild-type (WT) females, and decreased eukaryotic elongation factor 2 (eEF2) phosphorylation in the PFC of male and female WT mice, indicating that agmatine might be a fast-acting antidepressant with N-methyl-D-aspartate (NMDA) receptor antagonist properties. Collectively, these findings implicate Agmat in the depressive-like phenotype of Crtc1(-/-) mice, refine current understanding of the agmatinergic system in the brain and highlight its putative role in major depression.

  6. Guanosine tetraphosphate as a global regulator of bacterial RNA synthesis: a model involving RNA polymerase pausing and queuing.

    Science.gov (United States)

    Bremer, H; Ehrenberg, M

    1995-05-17

    A recently reported comparison of stable RNA (rRNA, tRNA) and mRNA synthesis rates in ppGpp-synthesizing and ppGpp-deficient (delta relA delta spoT) bacteria has suggested that ppGpp inhibits transcription initiation from stable RNA promoters, as well as synthesis of (bulk) mRNA. Inhibition of stable RNA synthesis occurs mainly during slow growth of bacteria when cytoplasmic levels of ppGpp are high. In contrast, inhibition of mRNA occurs mainly during fast growth when ppGpp levels are low, and it is associated with a partial inactivation of RNA polymerase. To explain these observations it has been proposed that ppGpp causes transcriptional pausing and queuing during the synthesis of mRNA. Polymerase queuing requires high rates of transcription initiation in addition to polymerase pausing, and therefore high concentrations of free RNA polymerase. These conditions are found in fast growing bacteria. Furthermore, the RNA polymerase queues lead to a promoter blocking when RNA polymerase molecules stack up from the pause site back to the (mRNA) promoter. This occurs most frequently at pause sites close to the promoter. Blocking of mRNA promoters diverts RNA polymerase to stable RNA promoters. In this manner ppGpp could indirectly stimulate synthesis of stable RNA at high growth rates. In the present work a mathematical analysis, based on the theory of queuing, is presented and applied to the global control of transcription in bacteria. This model predicts the in vivo distribution of RNA polymerase over stable RNA and mRNA genes for both ppGpp-synthesizing and ppGpp-deficient bacteria in response to different environmental conditions. It also shows how small changes in basal ppGpp concentrations can produce large changes in the rate of stable RNA synthesis.

  7. Involvement of necroptosis, a newly recognized cell death type, in steroid-induced osteonecrosis in a rabbit model

    Science.gov (United States)

    Ichiseki, Toru; Ueda, Shusuke; Ueda, Yoshimichi; Tuchiya, Masanobu; Kaneuji, Ayumi; Kawahara, Norio

    2017-01-01

    We investigated the role of programmed necrosis (necroptosis), a newly recognized form of cell necrosis that has been implicated in the development of steroid-induced osteonecrosis. We used an osteonecrosis model in which 30 Japanese white rabbits each weighing 3.5kg were injected once with methylprednisolone at 20 mg/kg body weight into the right gluteal muscle. Ten animals killed 14 days thereafter were designated as S14d groups, while another 10 animals injected with necroptosis, a specific inhibitor of necrostatin-1 i.v. at 1.65mg/kg on the same day as the steroid were also killed on the 14th day and designated as SN14d group. As a control, 10 animals injected only with physiological saline were studied as N group. After the animals were sacrificed the bilateral femoral bone was examined histopathologically and the presence of osteonecrosis determined. Furthermore, animals subjected to the same treatment and killed on the 3rd day after drug administration were set up as S3d group and SN3d group, and Western blotting of Receptor-interacting protein ( RIP ) 1 and RIP3 in femoral bone performed. The osteonecrosis rate was 70% in S14d group, and 0% in both N and SN groups. In 2 of 10 animals in SN group fatty marrow was found. On Western blotting significantly increased expression of both RIP1 and RIP3 was noted in S3d group, confirming that Nec-1 was suppressed. Necroptosis mediated by RIP1 and RIP3 expression was thought to be implicated in the development of steroid-induced osteonecrosis. Also, by suppressing expression of RIP1 and 3 with the administration of Nec-1 the osteonecrosis rate was significantly decreased. These results suggest that necroptosis may have potential as a novel target for both elucidating the mechanisms underlying steroid-induced osteonecrosis and establishing more effective prophylactic countermeasures. PMID:28260985

  8. BDNF prevents NMDA-induced toxicity in models of Huntington's disease: the effects are genotype specific and adenosine A2A receptor is involved.

    Science.gov (United States)

    Martire, Alberto; Pepponi, Rita; Domenici, Maria Rosaria; Ferrante, Antonella; Chiodi, Valentina; Popoli, Patrizia

    2013-04-01

    NMDA receptor-mediated excitotoxicity is thought to play a pivotal role in the pathogenesis of Huntington's disease (HD). The neurotrophin brain-derived neurotrophic factor (BDNF), which is also highly involved in HD and whose effects are modulated by adenosine A2 ARs, influences the activity and expression of striatal NMDA receptors. In electrophysiology experiments, we investigated the role of BDNF toward NMDA-induced effects in HD models, and the possible involvement of A2ARs. In corticostriatal slices from wild-type mice and age-matched symptomatic R6/2 mice (a model of HD), NMDA application (75 μM) induced a transient or a permanent (i.e., toxic) reduction of field potential amplitude, respectively. BDNF (10 ng/mL) potentiated NMDA effects in wild-type, while it protected from NMDA toxicity in R6/2 mice. Both effects of BDNF were prevented by A2 AR blockade. The protective effect of BDNF against NMDA-induced toxicity was reproduced in a cellular model of HD. These findings may have very important implications for the neuroprotective potential of BDNF and A2 AR ligands in HD.

  9. Multiple solutions and numerical analysis to the dynamic and stationary models coupling a delayed energy balance model involving latent heat and discontinuous albedo with a deep ocean.

    Science.gov (United States)

    Díaz, J I; Hidalgo, A; Tello, L

    2014-10-08

    We study a climatologically important interaction of two of the main components of the geophysical system by adding an energy balance model for the averaged atmospheric temperature as dynamic boundary condition to a diagnostic ocean model having an additional spatial dimension. In this work, we give deeper insight than previous papers in the literature, mainly with respect to the 1990 pioneering model by Watts and Morantine. We are taking into consideration the latent heat for the two phase ocean as well as a possible delayed term. Non-uniqueness for the initial boundary value problem, uniqueness under a non-degeneracy condition and the existence of multiple stationary solutions are proved here. These multiplicity results suggest that an S-shaped bifurcation diagram should be expected to occur in this class of models generalizing previous energy balance models. The numerical method applied to the model is based on a finite volume scheme with nonlinear weighted essentially non-oscillatory reconstruction and Runge-Kutta total variation diminishing for time integration.

  10. Multiple solutions and numerical analysis to the dynamic and stationary models coupling a delayed energy balance model involving latent heat and discontinuous albedo with a deep ocean

    Science.gov (United States)

    Díaz, J. I.; Hidalgo, A.; Tello, L.

    2014-01-01

    We study a climatologically important interaction of two of the main components of the geophysical system by adding an energy balance model for the averaged atmospheric temperature as dynamic boundary condition to a diagnostic ocean model having an additional spatial dimension. In this work, we give deeper insight than previous papers in the literature, mainly with respect to the 1990 pioneering model by Watts and Morantine. We are taking into consideration the latent heat for the two phase ocean as well as a possible delayed term. Non-uniqueness for the initial boundary value problem, uniqueness under a non-degeneracy condition and the existence of multiple stationary solutions are proved here. These multiplicity results suggest that an S-shaped bifurcation diagram should be expected to occur in this class of models generalizing previous energy balance models. The numerical method applied to the model is based on a finite volume scheme with nonlinear weighted essentially non-oscillatory reconstruction and Runge–Kutta total variation diminishing for time integration. PMID:25294969

  11. Do not forget the professional--the value of the FIRST model for guiding the structural involvement of patients in rheumatology research.

    Science.gov (United States)

    de Wit, Maarten P T; Elberse, Janneke E; Broerse, Jacqueline E W; Abma, Tineke A

    2015-08-01

    The FIRST model describes five practical components that enable equal collaboration between patients and professionals in clinical rheumatology research: Facilitate, identify, respect, support and training. To assess the value of this model as a framework for setting up and guiding the structural involvement of people with arthritis in health research. The FIRST model was used as a framework during the guidance of a network of patient research partners and clinical rheumatology departments in the Netherlands. A 'monitoring and evaluation' approach was used to study the network over a period of 2 years. Data were collected using mixed methods and subjected to a directed content analysis. The FIRST components structured the data analysis. During monitoring meetings, refined and additional descriptors for each component were formulated and added if new items were found. The FIRST model helps to guide and foster structural partnerships between patients and professionals in health research projects. However, it should be broadened to emphasize the pivotal role of the principal investigator regarding the facilitation and support of patient research partners, to recognize the requirements of professionals for training and coaching and to capture the dynamics of collaboration, mutual learning processes and continuous reflection. FIRST is a good model to implement sustainable relationships between patients and researchers. It will benefit from further refinement by acknowledging the dynamics of collaboration and including the concept of reflection and relational empowerment. The reciprocal character of the five components, including training and support of researchers, should be incorporated. © 2013 John Wiley & Sons Ltd.

  12. Determination of the Support Level of Local Organizations in a Model Forest Initiative: Do Local Stakeholders Have Willingness to Be Involved in the Model Forest Development?

    Directory of Open Access Journals (Sweden)

    Ahmet Tolunay

    2014-10-01

    Full Text Available Voluntary cooperation and the support of stakeholders carry a major importance in the development of Model Forests. The identification of the support level of local organizations as stakeholders in the Bucak Model Forest initiative, located in the Mediterranean region of Turkey, constitutes the theme of this study. Within this scope, the views of the stakeholders comprising local government units (LGUs, non-governmental organizations (NGOs, village councils (VCs, professional organizations (POs and forest products enterprises (FPEs located in the district of Bucak were collected by utilizing a survey technique. The data were analysed by using non-parametric statistical analyses due to the absence of a normal distribution. The results show that the information provided about the Model Forest concept to the stakeholders located in the district on the Bucak Model Forest initiative was identified as a factor impacting the support level. Moreover, it was also observed that the stakeholders were more willing to provide advisory support rather than financial support. NGOs and VCs were identified as stakeholders who could not provide financial support due to their restricted budgets. We discuss the benefits for a Model Forest initiative of establishing international cooperation to strengthen the local and regional sustainable development process.

  13. In silico Comparative Modeling of PapA1 and PapA2 Proteins Involved in Mycobacterium Tuberculosis Sulfolipid-1 Biosynthesis Pathway

    Directory of Open Access Journals (Sweden)

    Rana Adnan Tahir

    2012-09-01

    Full Text Available Tuberculosis is one of the most serious health problems, as globally; around 2 billion or one third of the world's total population has been infected with Mycobacterium tuberculosis. Mycobacterium tuberculosis is a unique among bacterial pathogens in that it displays a wide array of complex lipids and lipoglycans on its cell surface. One such glycolipid, sulfolipid-1 (SL-1, is the most sulfatide, consists of a trehalose core, four fatty acyl groups, and a sulfate ester. Several proteins involved in SL-1 biosynthesis have been identified, the enzymes that acylate the T2S core to form SL1278 and SL-1, and the biosynthetic order of these acylation reactions, are unknown. Here we studied the in silico identification of PapA2 and PapA1, proteins responsible for the sequential acylation of T2S to form SL1278 and are essential for SL-1 biosynthesis, by applying different bioinformatics tools. Benchmark, of 3 different homology modeling programs Modeller, Swiss-Model (Deep View, and ESyPred3D, has been performed used to transform the alignment to a 3D model. The 3D structures of targeted proteins were evaluated by evaluation tools, ANOLEA and Verify3D. It is concluded that in SL-1 biosynthesis pathway, PapA1 and PapA2 proteins could be used as drug target, drug lead design and to find out the other proteins involved in this pathway that not yet have been identified and may be used to the cure of tuberculosis infection.

  14. Acetylome analysis reveals the involvement of lysine acetylation in photosynthesis and carbon metabolism in the model cyanobacterium Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Mo, Ran; Yang, Mingkun; Chen, Zhuo; Cheng, Zhongyi; Yi, Xingling; Li, Chongyang; He, Chenliu; Xiong, Qian; Chen, Hui; Wang, Qiang; Ge, Feng

    2015-02-06

    Cyanobacteria are the oldest known life form inhabiting Earth and the only prokaryotes capable of performing oxygenic photosynthesis. Synechocystis sp. PCC 6803 (Synechocystis) is a model cyanobacterium used extensively in research on photosynthesis and environmental adaptation. Posttranslational protein modification by lysine acetylation plays a critical regulatory role in both eukaryotes and prokaryotes; however, its extent and function in cyanobacteria remain unexplored. Herein, we performed a global acetylome analysis on Synechocystis through peptide prefractionation, antibody enrichment, and high accuracy LC-MS/MS analysis; identified 776 acetylation sites on 513 acetylated proteins; and functionally categorized them into an interaction map showing their involvement in various biological processes. Consistent with previous reports, a large fraction of the acetylation sites are present on proteins involved in cellular metabolism. Interestingly, for the first time, many proteins involved in photosynthesis, including the subunits of phycocyanin (CpcA, CpcB, CpcC, and CpcG) and allophycocyanin (ApcA, ApcB, ApcD, ApcE, and ApcF), were found to be lysine acetylated, suggesting that lysine acetylation may play regulatory roles in the photosynthesis process. Six identified acetylated proteins associated with photosynthesis and carbon metabolism were further validated by immunoprecipitation and Western blotting. Our data provide the first global survey of lysine acetylation in cyanobacteria and reveal previously unappreciated roles of lysine acetylation in the regulation of photosynthesis. The provided data set may serve as an important resource for the functional analysis of lysine acetylation in cyanobacteria and facilitate the elucidation of the entire metabolic networks and photosynthesis process in this model cyanobacterium.

  15. Vascular smooth muscle G(q) signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension.

    Science.gov (United States)

    Harris, David M; Cohn, Heather I; Pesant, Stéphanie; Zhou, Rui-Hai; Eckhart, Andrea D

    2007-11-01

    More than 30% of the US population has high blood pressure (BP), and less than a third of people treated for hypertension have it controlled. In addition, the etiology of most high BP is not known. Having a better understanding of the mechanisms underlying hypertension could potentially increase the effectiveness of treatment. Because G(q) signaling mediates vasoconstriction and vascular function can cause BP abnormalities, we were interested in determining the role of vascular smooth muscle (VSM) G(q) signaling in two divergent models of hypertension: a renovascular model of hypertension through renal artery stenosis and a genetic model of hypertension using mice with VSM-derived high BP. Inhibition of VSM G(q) signaling attenuated BP increases induced by renal artery stenosis to a similar extent as losartan, an ANG II receptor blocker and current antihypertensive therapy. Inhibition of G(q) signaling also attenuated high BP in our genetic VSM-derived hypertensive model. In contrast, BP remained elevated 25% following treatment with losartan, and prazosin, an alpha(1)-adrenergic receptor antagonist, only decreased BP by 35%. Inhibition of G(q) signaling attenuated VSM reactivity to ANG II and resulted in a 2.4-fold rightward shift in EC(50). We also determined that inhibition of G(q) signaling was able to reverse VSM hypertrophy in the genetic VSM-derived hypertensive model. These results suggest that G(q) signaling is an important signaling pathway in two divergent models of hypertension and, perhaps, optimization of antihypertensive therapy could occur with the identification of particular G(q)-coupled receptors involved.

  16. N-methyl-D-aspartate receptor NR2B subunit involved in depression-like behaviours in lithium chloride-pilocarpine chronic rat epilepsy model.

    Science.gov (United States)

    Peng, Wei-Feng; Ding, Jing; Li, Xin; Fan, Fan; Zhang, Qian-Qian; Wang, Xin

    2016-01-01

    Depression is a common comorbidity in patients with epilepsy with unclear mechanisms. This study is to explore the role of glutamate N-methyl-D-aspartate (NMDA) receptor NR1, NR2A and NR2B subunits in epilepsy-associated depression. Lithium chloride (Licl)-pilocarpine chronic rat epilepsy model was established and rats were divided into epilepsy with depression (EWD) and epilepsy without depression (EWND) subgroups based on forced swim test. Expression of NMDA receptor NR1, NR2A and NR2B subunits was measured by western blot and immunofluorescence methods. The immobility time (IMT) was significantly greater in Licl-pilocarpine model group than in Control group, which was also greater in EWD group than in EWND group. No differences of spontaneous recurrent seizure (SRS) counts over two weeks and latency were found between EWD and EWND groups. The number of NeuN positive cells was significantly less in Licl-pilocarpine model group than in Control group, but had no difference between EWD and EWND groups. The ratios of phosphorylated NR1 (p-NR1)/NR1 and p-NR2B/NR2B were significantly greater in the hippocampus in EWD group than in EWND group. Moreover, the expression of p-NR1 and p-NR2B in the CA1 subfield of hippocampus were both greater in Licl-pilocarpine model group than Control group. Selective blockage of NR2B subunit with ifenprodil could alleviate depression-like behaviours of Licl-pilocarpine rat epilepsy model. In conclusion, glutamate NMDA receptor NR2B subunit was involved in promoting depression-like behaviours in the Licl-pilocarpine chronic rat epilepsy model and might be a target for treating epilepsy-associated depression.

  17. Review of Real-Time Simulator and the Steps Involved for Implementation of a Model from MATLAB/SIMULINK to Real-Time

    Science.gov (United States)

    Mikkili, Suresh; Panda, Anup Kumar; Prattipati, Jayanthi

    2014-07-01

    Nowadays the researchers want to develop their model in real-time environment. Simulation tools have been widely used for the design and improvement of electrical systems since the mid twentieth century. The evolution of simulation tools has progressed in step with the evolution of computing technologies. In recent years, computing technologies have improved dramatically in performance and become widely available at a steadily decreasing cost. Consequently, simulation tools have also seen dramatic performance gains and steady cost decreases. Researchers and engineers now have the access to affordable, high performance simulation tools that were previously too cost prohibitive, except for the largest manufacturers. This work has introduced a specific class of digital simulator known as a real-time simulator by answering the questions "what is real-time simulation", "why is it needed" and "how it works". The latest trend in real-time simulation consists of exporting simulation models to FPGA. In this article, the Steps involved for implementation of a model from MATLAB to REAL-TIME are provided in detail.

  18. Alteration in Marrow Stromal Microenvironment and Apoptosis Mechanisms Involved in Aplastic Anemia: An Animal Model to Study the Possible Disease Pathology

    Directory of Open Access Journals (Sweden)

    Sumanta Chatterjee

    2010-01-01

    Full Text Available Aplastic anemia (AA is a heterogeneous disorder of bone marrow failure syndrome. Suggested mechanisms include a primary stem cell deficiency or defect, a secondary stem cell defect due to abnormal regulation between cell death and differentiation, or a deficient microenvironment. In this study, we have tried to investigate the alterations in hematopoietic microenvironment and underlying mechanisms involved in such alterations in an animal model of drug induced AA. We presented the results of studying long term marrow culture, marrow ultra-structure, marrow adherent and hematopoietic progenitor cell colony formation, flowcytometric analysis of marrow stem and stromal progenitor populations and apoptosis mechanism involved in aplastic anemia. The AA marrow showed impairment in cellular proliferation and maturation and failed to generate a functional stromal microenvironment even after 19 days of culture. Ultra-structural analysis showed a degenerated and deformed marrow cellular association in AA. Colony forming units (CFUs were also severely reduced in AA. Significantly decreased marrow stem and stromal progenitor population with subsequently increased expression levels of both the extracellular and intracellular apoptosis inducer markers in the AA marrow cells essentially pointed towards the defective hematopoiesis; moreover, a deficient and apoptotic microenvironment and the microenvironmental components might have played the important role in the possible pathogenesis of AA.

  19. Heterogeneity in the Relationship of Substance Use to Risky Sexual Behavior Among Justice-Involved Youth: A Regression Mixture Modeling Approach.

    Science.gov (United States)

    Schmiege, Sarah J; Bryan, Angela D

    2016-04-01

    Justice-involved adolescents engage in high levels of risky sexual behavior and substance use, and understanding potential relationships among these constructs is important for effective HIV/STI prevention. A regression mixture modeling approach was used to determine whether subgroups could be identified based on the regression of two indicators of sexual risk (condom use and frequency of intercourse) on three measures of substance use (alcohol, marijuana and hard drugs). Three classes were observed among n = 596 adolescents on probation: none of the substances predicted outcomes for approximately 18 % of the sample; alcohol and marijuana use were predictive for approximately 59 % of the sample, and marijuana use and hard drug use were predictive in approximately 23 % of the sample. Demographic, individual difference, and additional sexual and substance use risk variables were examined in relation to class membership. Findings are discussed in terms of understanding profiles of risk behavior among at-risk youth.

  20. Clustering consumers based on trust, confidence and giving behaviour: data-driven model building for charitable involvement in the Australian not-for-profit sector.

    Directory of Open Access Journals (Sweden)

    Natalie Jane de Vries

    Full Text Available Organisations in the Not-for-Profit and charity sector face increasing competition to win time, money and efforts from a common donor base. Consequently, these organisations need to be more proactive than ever. The increased level of communications between individuals and organisations today, heightens the need for investigating the drivers of charitable giving and understanding the various consumer groups, or donor segments, within a population. It is contended that `trust' is the cornerstone of the not-for-profit sector's survival, making it an inevitable topic for research in this context. It has become imperative for charities and not-for-profit organisations to adopt for-profit's research, marketing and targeting strategies. This study provides the not-for-profit sector with an easily-interpretable segmentation method based on a novel unsupervised clustering technique (MST-kNN followed by a feature saliency method (the CM1 score. A sample of 1,562 respondents from a survey conducted by the Australian Charities and Not-for-profits Commission is analysed to reveal donor segments. Each cluster's most salient features are identified using the CM1 score. Furthermore, symbolic regression modelling is employed to find cluster-specific models to predict `low' or `high' involvement in clusters. The MST-kNN method found seven clusters. Based on their salient features they were labelled as: the `non-institutionalist charities supporters', the `resource allocation critics', the `information-seeking financial sceptics', the `non-questioning charity supporters', the `non-trusting sceptics', the `charity management believers' and the `institutionalist charity believers'. Each cluster exhibits their own characteristics as well as different drivers of `involvement'. The method in this study provides the not-for-profit sector with a guideline for clustering, segmenting, understanding and potentially targeting their donor base better. If charities and not

  1. A Quantitative Risk Assessment Model Involving Frequency and Threat Degree under Line-of-Business Services for Infrastructure of Emerging Sensor Networks.

    Science.gov (United States)

    Jing, Xu; Hu, Hanwen; Yang, Huijun; Au, Man Ho; Li, Shuqin; Xiong, Naixue; Imran, Muhammad; Vasilakos, Athanasios V

    2017-03-21

    The prospect of Line-of-Business Services (LoBSs) for infrastructure of Emerging Sensor Networks (ESNs) is exciting. Access control remains a top challenge in this scenario as the service provider's server contains a lot of valuable resources. LoBSs' users are very diverse as they may come from a wide range of locations with vastly different characteristics. Cost of joining could be low and in many cases, intruders are eligible users conducting malicious actions. As a result, user access should be adjusted dynamically. Assessing LoBSs' risk dynamically based on both frequency and threat degree of malicious operations is therefore necessary. In this paper, we proposed a Quantitative Risk Assessment Model (QRAM) involving frequency and threat degree based on value at risk. To quantify the threat degree as an elementary intrusion effort, we amend the influence coefficient of risk indexes in the network security situation assessment model. To quantify threat frequency as intrusion trace effort, we make use of multiple behavior information fusion. Under the influence of intrusion trace, we adapt the historical simulation method of value at risk to dynamically access LoBSs' risk. Simulation based on existing data is used to select appropriate parameters for QRAM. Our simulation results show that the duration influence on elementary intrusion effort is reasonable when the normalized parameter is 1000. Likewise, the time window of intrusion trace and the weight between objective risk and subjective risk can be set to 10 s and 0.5, respectively. While our focus is to develop QRAM for assessing the risk of LoBSs for infrastructure of ESNs dynamically involving frequency and threat degree, we believe it is also appropriate for other scenarios in cloud computing.

  2. A Quantitative Risk Assessment Model Involving Frequency and Threat Degree under Line-of-Business Services for Infrastructure of Emerging Sensor Networks

    Science.gov (United States)

    Jing, Xu; Hu, Hanwen; Yang, Huijun; Au, Man Ho; Li, Shuqin; Xiong, Naixue; Imran, Muhammad; Vasilakos, Athanasios V.

    2017-01-01

    The prospect of Line-of-Business Services (LoBSs) for infrastructure of Emerging Sensor Networks (ESNs) is exciting. Access control remains a top challenge in this scenario as the service provider’s server contains a lot of valuable resources. LoBSs’ users are very diverse as they may come from a wide range of locations with vastly different characteristics. Cost of joining could be low and in many cases, intruders are eligible users conducting malicious actions. As a result, user access should be adjusted dynamically. Assessing LoBSs’ risk dynamically based on both frequency and threat degree of malicious operations is therefore necessary. In this paper, we proposed a Quantitative Risk Assessment Model (QRAM) involving frequency and threat degree based on value at risk. To quantify the threat degree as an elementary intrusion effort, we amend the influence coefficient of risk indexes in the network security situation assessment model. To quantify threat frequency as intrusion trace effort, we make use of multiple behavior information fusion. Under the influence of intrusion trace, we adapt the historical simulation method of value at risk to dynamically access LoBSs’ risk. Simulation based on existing data is used to select appropriate parameters for QRAM. Our simulation results show that the duration influence on elementary intrusion effort is reasonable when the normalized parameter is 1000. Likewise, the time window of intrusion trace and the weight between objective risk and subjective risk can be set to 10 s and 0.5, respectively. While our focus is to develop QRAM for assessing the risk of LoBSs for infrastructure of ESNs dynamically involving frequency and threat degree, we believe it is also appropriate for other scenarios in cloud computing. PMID:28335569

  3. Clustering Consumers Based on Trust, Confidence and Giving Behaviour: Data-Driven Model Building for Charitable Involvement in the Australian Not-For-Profit Sector

    Science.gov (United States)

    de Vries, Natalie Jane; Reis, Rodrigo; Moscato, Pablo

    2015-01-01

    Organisations in the Not-for-Profit and charity sector face increasing competition to win time, money and efforts from a common donor base. Consequently, these organisations need to be more proactive than ever. The increased level of communications between individuals and organisations today, heightens the need for investigating the drivers of charitable giving and understanding the various consumer groups, or donor segments, within a population. It is contended that `trust' is the cornerstone of the not-for-profit sector's survival, making it an inevitable topic for research in this context. It has become imperative for charities and not-for-profit organisations to adopt for-profit's research, marketing and targeting strategies. This study provides the not-for-profit sector with an easily-interpretable segmentation method based on a novel unsupervised clustering technique (MST-kNN) followed by a feature saliency method (the CM1 score). A sample of 1,562 respondents from a survey conducted by the Australian Charities and Not-for-profits Commission is analysed to reveal donor segments. Each cluster's most salient features are identified using the CM1 score. Furthermore, symbolic regression modelling is employed to find cluster-specific models to predict `low' or `high' involvement in clusters. The MST-kNN method found seven clusters. Based on their salient features they were labelled as: the `non-institutionalist charities supporters', the `resource allocation critics', the `information-seeking financial sceptics', the `non-questioning charity supporters', the `non-trusting sceptics', the `charity management believers' and the `institutionalist charity believers'. Each cluster exhibits their own characteristics as well as different drivers of `involvement'. The method in this study provides the not-for-profit sector with a guideline for clustering, segmenting, understanding and potentially targeting their donor base better. If charities and not

  4. Clustering consumers based on trust, confidence and giving behaviour: data-driven model building for charitable involvement in the Australian not-for-profit sector.

    Science.gov (United States)

    de Vries, Natalie Jane; Reis, Rodrigo; Moscato, Pablo

    2015-01-01

    Organisations in the Not-for-Profit and charity sector face increasing competition to win time, money and efforts from a common donor base. Consequently, these organisations need to be more proactive than ever. The increased level of communications between individuals and organisations today, heightens the need for investigating the drivers of charitable giving and understanding the various consumer groups, or donor segments, within a population. It is contended that `trust' is the cornerstone of the not-for-profit sector's survival, making it an inevitable topic for research in this context. It has become imperative for charities and not-for-profit organisations to adopt for-profit's research, marketing and targeting strategies. This study provides the not-for-profit sector with an easily-interpretable segmentation method based on a novel unsupervised clustering technique (MST-kNN) followed by a feature saliency method (the CM1 score). A sample of 1,562 respondents from a survey conducted by the Australian Charities and Not-for-profits Commission is analysed to reveal donor segments. Each cluster's most salient features are identified using the CM1 score. Furthermore, symbolic regression modelling is employed to find cluster-specific models to predict `low' or `high' involvement in clusters. The MST-kNN method found seven clusters. Based on their salient features they were labelled as: the `non-institutionalist charities supporters', the `resource allocation critics', the `information-seeking financial sceptics', the `non-questioning charity supporters', the `non-trusting sceptics', the `charity management believers' and the `institutionalist charity believers'. Each cluster exhibits their own characteristics as well as different drivers of `involvement'. The method in this study provides the not-for-profit sector with a guideline for clustering, segmenting, understanding and potentially targeting their donor base better. If charities and not

  5. Endoplasmic Reticulum Is Involved in Myocardial Injury in a Miniature Swine Model of Coronary Artery Stenosis Exposed to Acceleration-Associated Stress

    Science.gov (United States)

    Zhang, Haitao; Chai, Meng; Liu, Chaozhong; Sun, Jinjin; Huang, Congchun; Yu, Xinya; Tian, Yi; Luo, Huilan

    2015-01-01

    This study aimed to investigate the effects of myocardial injury in a minimally-invasive miniature swine model with different levels of coronary artery stenosis (CAS) and exposed to maximal tolerated +Gz. Proximal left anterior descending branch was ligated in 20 swine. Five swine underwent a sham operation. A trapezoid acceleration curve was used for +Gz stress. Pathological changes of myocardial tissue were detected by H&E staining. Apoptotic cardiomyocytes were detected by TUNEL. GRP78 and CHOP were investigated by immunohistochemistry and western blot. CAS models were successful in 18 animals.Compared with the sham-operated group (+8.00±0.71 Gz), the maximal tolerated +Gz values of the moderate stenosis (+6.00±0.89 Gz, Pstenosis groups (+5.20±0.84 Gz, Pstenosis group (60.50±9.35%, Pstenosis groups (0.35±0.04), while expression was high in the moderate (0.72±0.04, Pstenosis groups (0.65±0.07, Pstenosis groups. These results indicated that Under maximum exposure to +Gz stress, different levels of CAS led to different levels of myocardial injury. Endoplasmic reticulum response is involved in the apoptosis of cardiomyocytes after +Gz stress. PMID:26167928

  6. The proinflammatory RAGE/NF-κB pathway is involved in neuronal damage and reactive gliosis in a model of sleep apnea by intermittent hypoxia.

    Science.gov (United States)

    Angelo, Maria Florencia; Aguirre, Alejandra; Avilés Reyes, Rolando X; Villarreal, Alejandro; Lukin, Jerónimo; Melendez, Matías; Vanasco, Virginia; Barker, Phil; Alvarez, Silvia; Epstein, Alberto; Jerusalinsky, Diana; Ramos, Alberto Javier

    2014-01-01

    Sleep apnea (SA) causes long-lasting changes in neuronal circuitry, which persist even in patients successfully treated for the acute effects of the disease. Evidence obtained from the intermittent hypoxia (IH) experimental model of SA has shown neuronal death, impairment in learning and memory and reactive gliosis that may account for cognitive and structural alterations observed in human patients. However, little is known about the mechanism controlling these deleterious effects that may be useful as therapeutic targets in SA. The Receptor for Advanced Glycation End products (RAGE) and its downstream effector Nuclear Factor Kappa B (NF-κB) have been related to neuronal death and astroglial conversion to the pro-inflammatory neurodegenerative phenotype. RAGE expression and its ligand S100B were shown to be increased in experimental models of SA. We here used dissociated mixed hippocampal cell cultures and male Wistar rats exposed to IH cycles and observed that NF-κB is activated in glial cells and neurons after IH. To disclose the relative contribution of the S100B/RAGE/NF-κB pathway to neuronal damage and reactive gliosis after IH we performed sequential loss of function studies using RAGE or S100B neutralizing antibodies, a herpes simplex virus (HSV)-derived amplicon vector that induces the expression of RAGEΔcyto (dominant negative RAGE) and a chemical blocker of NF-κB. Our results show that NF-κB activation peaks 3 days after IH exposure, and that RAGE or NF-κB blockage during this critical period significantly improves neuronal survival and reduces reactive gliosis. Both in vitro and in vivo, S100B blockage altered reactive gliosis but did not have significant effects on neuronal survival. We conclude that both RAGE and downstream NF-κB signaling are centrally involved in the neuronal alterations found in SA models, and that blockage of these pathways is a tempting strategy for preventing neuronal degeneration and reactive gliosis in SA.

  7. Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model.

    Science.gov (United States)

    Vergo, Sandra; Craner, Matthew J; Etzensperger, Ruth; Attfield, Kathrine; Friese, Manuel A; Newcombe, Jia; Esiri, Margaret; Fugger, Lars

    2011-02-01

    Although there is growing evidence for a role of excess intracellular cations, particularly calcium ions, in neuronal and glial cell injury in multiple sclerosis, as well as in non-inflammatory neurological conditions, the molecular mechanisms involved are not fully determined. We previously showed that the acid-sensing ion channel 1 which, when activated under the acidotic tissue conditions found in inflammatory lesions opens to allow influx of sodium and calcium ions, contributes to axonal injury in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. However, the extent and cellular distribution of acid-sensing ion channel 1 expression in neurons and glia in inflammatory lesions is unknown and, crucially, acid-sensing ion channel 1 expression has not been determined in multiple sclerosis lesions. Here we studied acute and chronic experimental autoimmune encephalomyelitis and multiple sclerosis spinal cord and optic nerve tissues to describe in detail the distribution of acid-sensing ion channel 1 and its relationship with neuronal and glial damage. We also tested the effects of amiloride treatment on tissue damage in the mouse models. We found that acid-sensing ion channel 1 was upregulated in axons and oligodendrocytes within lesions from mice with acute experimental autoimmune encephalomyelitis and from patients with active multiple sclerosis. The expression of acid-sensing ion channel 1 was associated with axonal damage as indicated by co-localization with the axonal injury marker beta amyloid precursor protein. Moreover, blocking acid-sensing ion channel 1 with amiloride protected both myelin and neurons from damage in the acute model, and when given either at disease onset or, more clinically relevant, at first relapse, ameliorated disability in mice with chronic-relapsing experimental autoimmune encephalomyelitis. Together these findings suggest that blockade of acid-sensing ion channel 1 has the potential to provide both neuro

  8. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway

    Directory of Open Access Journals (Sweden)

    Hamed Shafaroodi

    2015-10-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP surgery in male NMRI mice (20-30 g. Pioglitazone (5,10 and 20 mg/kg was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily or aminoguanidine (1 mg/kg, daily with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  9. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway.

    Science.gov (United States)

    Shafaroodi, Hamed; Hassanipour, Mahsa; Mousavi, Zahra; Rahimi, Nastaran; Dehpour, Ahmad Reza

    2015-10-01

    Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP) surgery in male NMRI mice (20-30 g). Pioglitazone (5,10 and 20 mg/kg) was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg) significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily) or aminoguanidine (1 mg/kg, daily) with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  10. A new model involving ethylene, nitric oxide and Fe to explain the regulation of Fe-acquisition genes in Strategy I plants.

    Science.gov (United States)

    García, María J; Suárez, Vicente; Romera, Francisco J; Alcántara, Esteban; Pérez-Vicente, Rafael

    2011-05-01

    In previous work it has been shown that both ethylene and NO (nitric oxide) participate in a similar way in the up-regulation of several Fe-acquisition genes of Arabidopsis and other Strategy I plants. This raises the question as to whether NO acts through ethylene or ethylene acts through NO, or whether both act in conjunction. One possibility is that NO could increase ethylene production. Conversely, ethylene could increase NO production. By using Arabidopsis and cucumber plants, we have found that both possibilities occur: NO greatly induces the expression in roots of genes involved in ethylene synthesis: AtSAM1, AtSAM2, AtACS4, AtACS6, AtACO1, AtACO2, AtMTK; CsACS2 and CsACO2; on the other hand, ethylene greatly enhances NO production in the subapical region of the roots. These results suggest that each substance influences the production of the other and that both substances could be necessary for up-regulation of Fe-acquisition genes. This has been further confirmed in experiments with simultaneous application of the NO donor GSNO (S-nitrosoglutathione) and ethylene inhibitors; or with simultaneous application of the ethylene precursor ACC (1-aminocyclopropane-1-carboxylic acid) and an NO scavenger. Both GSNO and ACC enhanced ferric reductase activity in control plants, but not in those plants simultaneously treated with the ethylene inhibitors or the NO scavenger, respectively. To explain all these results and previous ones we have proposed a new model involving ethylene, NO, and Fe in the up-regulation of Fe-acquisition genes of Strategy I plants. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  11. A nootropic effect of Moringa oleifera on Ach and ChAT activity in colchicine induced experimental rat model of Alzheimer’s disease: Possible involvement of antioxidants

    Directory of Open Access Journals (Sweden)

    Chandan Roy

    2014-04-01

    Full Text Available Context: The fruit and leaf of Moringa oleifera (MO is an important ingredient of ‘Kusmanda lehyam’ (Ayurvedic medicine, which is widely used, in nervous disorders. Objective: To determine the cognition facilitating effect of MO leaf extract in colchicine induced experimental rat model of AD and to investigate the role of central cholinergic system in the nootropic effect of MO leaf extract with the possible involvement of antioxidant enzymes. Materials and methods: The behavior study, Acetylcholine concentration, cholineacetyl transferase activity, antioxidant level such as, superoxide dismutase (SOD, catalase (CAT, reduced glutathione (GSH and lipid peroxidation (LPO level were studied in different parts of the brain such as frontal cortex (FC and hippocampus (HPC in colchicine induced experimental Alzheimer rat model before and after treatment with MO. Results: MO (250 mg/kg p.o. induced statistically significant reversal of colchicine induced cognitive deficits. MO (250 mg/kg p.o. markedly induced frontal, cortical and hippocampal concentrations of Ach and ChAt activity, the effects being statistically significant on days 7, 14 and 21 respectively. Moreover, MO significantly increased SOD, CAT, GSH activities and significantly decreased LPO level on day 7, 14 and 21 respectively. Discussion and conclusion: The aqueous pulp extract of MO (250 mg/kg body weight containing vit- A, C, E results significant protection in the level of antioxidant status in frontal cortex and hippocampus after a certain period of co administration on colchicine induced oxidative stress without causing any general and metabolic toxicity and possibly thereby induced frontal cortical and hippocampal concentration of Ach and ChAT activity.

  12. Decreased expression of proteins involved in energy metabolism in the hippocampal granular layer of rats submitted to the pilocarpine epilepsy model.

    Science.gov (United States)

    Araujo, Bruno; Torres, Laila; Stein, Mariana; Cabral, Francisco Romero; Herai, Roberto; Okamoto, Oswaldo; Cavalheiro, Esper

    2014-02-21

    Long-term structural and functional changes in the hippocampus have been identified as the primary physiopathological basis for temporal lobe epilepsy. These changes include reactive gliosis and granule cell axonal sprouting within the dentate gyrus. The intimate mechanisms of these changes are beginning to be revealed. Here, we show the possibility of using laser capture microdissection (LCM) to isolate the dentate granular cell layer of Wistar rats submitted to the pilocarpine model of epilepsy. Using two-dimensional gel electrophoresis (2-D PAGE) and mass spectrometry for laser-captured cells, we identified molecular events that could be altered as part of the epileptic pathogenic process. According to our results, eight proteins related to energy metabolism were differentially expressed between both the control and pilocarpine-treated animals. These results provide, for the first time, new molecular insights into the altered protein profile of the epileptogenic dentate gyrus and can contribute to a better understanding of the phenomena involved in the genesis and maintenance of the epileptic state.

  13. Autophagy induction by leptin contributes to suppression of apoptosis in cancer cells and xenograft model: involvement of p53/FoxO3A axis.

    Science.gov (United States)

    Nepal, Saroj; Kim, Mi Jin; Hong, Jin Tae; Kim, Sang Hyun; Sohn, Dong-Hwan; Lee, Sung Hee; Song, Kyung; Choi, Dong Young; Lee, Eung Seok; Park, Pil-Hoon

    2015-03-30

    Leptin, a hormone mainly produced from adipose tissue, has been shown to induce proliferation of cancer cells. However, the molecular mechanisms underlying leptin-induced tumor progression have not been clearly elucidated. In the present study, we investigated the role of autophagy in leptin-induced cancer cell proliferation using human hepatoma (HepG2) and breast cancer cells (MCF-7), and tumor growth in a xenograft model. Herein, we showed that leptin treatment caused autophagy induction as assessed by increase in expression of autophagy-related genes, including beclin-1, Atg5 and LC3 II, further induction of autophagosome formation and autophagic flux. Interestingly, inhibition of autophagic process by treatment with inhibitors and LC3B gene silencing blocked leptin-induced increase in cell number and suppression of apoptosis, indicating a crucial role of autophagy in leptin-induced tumor progression. Moreover, gene silencing of p53 or FoxO3A prevented leptin-induced LC3 II protein expression, suggesting an involvement of p53/FoxO3A axis in leptin-induced autophagy activation. Leptin administration also accelerated tumor growth in BALB/c nude mice, which was found to be autophagy dependent. Taken together, our results demonstrate that leptin-induced tumor growth is mediated by autophagy induction and autophagic process would be a promising target to regulate development of cancer caused by leptin production.

  14. Model of socio-cultural dimensions involved in adherence to antiretroviral therapy for HIV/AIDS in public health care centers in Chile.

    Science.gov (United States)

    Stuardo Ávila, Valeria; Manriquez Urbina, Jose Manuel; Fajreldin Chuaqui, Valentina; Belmar Prieto, Julieta; Valenzuela Santibáñez, Victoria

    2016-11-01

    In Chile, over 14,000 adults are living with HIV receive antiretroviral therapy (HAART). Adequate adherence to HAART has a major impact on survival. There is little consensus on the causes of poor adherence, due to the unique and diverse sociocultural parameters involved in the issue. The objective of this study was to identify sociocultural dimensions that serve as barriers or facilitators to HAART adherence among persons living with HIV/AIDS (PLHIV) in Chile. A qualitative study design, with an exploratory followed by a descriptive phase was conducted. The study population consisted of adults living with HIV/AIDS, with and without HAART. A theoretical sample was designed and three gender profiles defined: women, men, and transwomen. Data collection methods included in-depth interviews by anthropologists in seven public health care centers for PLHIV. The model of sociocultural dimensions indicated that factors associated with family, expectations, gender/sexuality, affect, relationship with HIV, HAART, work, social support and networks, and stigma and discrimination influenced adherence, with different patterns among profiles. This study found that adherence is a dynamic category. It is crucial to consider sociocultural factors in developing strategies to improve HAART adherence.

  15. Autophagy induction by leptin contributes to suppression of apoptosis in cancer cells and xenograft model: Involvement of p53/FoxO3A axis

    Science.gov (United States)

    Nepal, Saroj; Kim, Mi Jin; Hong, Jin Tae; Kim, Sang Hyun; Sohn, Dong-Hwan; Lee, Sung Hee; Song, Kyung; Choi, Dong Young; Lee, Eung Seok; Park, Pil-Hoon

    2015-01-01

    Leptin, a hormone mainly produced from adipose tissue, has been shown to induce proliferation of cancer cells. However, the molecular mechanisms underlying leptin-induced tumor progression have not been clearly elucidated. In the present study, we investigated the role of autophagy in leptin-induced cancer cell proliferation using human hepatoma (HepG2) and breast cancer cells (MCF-7), and tumor growth in a xenograft model. Herein, we showed that leptin treatment caused autophagy induction as assessed by increase in expression of autophagy-related genes, including beclin-1, Atg5 and LC3 II, further induction of autophagosome formation and autophagic flux. Interestingly, inhibition of autophagic process by treatment with inhibitors and LC3B gene silencing blocked leptin-induced increase in cell number and suppression of apoptosis, indicating a crucial role of autophagy in leptin-induced tumor progression. Moreover, gene silencing of p53 or FoxO3A prevented leptin-induced LC3 II protein expression, suggesting an involvement of p53/FoxO3A axis in leptin-induced autophagy activation. Leptin administration also accelerated tumor growth in BALB/c nude mice, which was found to be autophagy dependent. Taken together, our results demonstrate that leptin-induced tumor growth is mediated by autophagy induction and autophagic process would be a promising target to regulate development of cancer caused by leptin production. PMID:25704884

  16. Caffeine prevents antihyperalgesic effect of gabapentin in an animal model of CRPS-I: evidence for the involvement of spinal adenosine A1 receptor.

    Science.gov (United States)

    Martins, Daniel F; Prado, Marcos R B; Daruge-Neto, Eduardo; Batisti, Ana P; Emer, Aline A; Mazzardo-Martins, Leidiane; Santos, Adair R S; Piovezan, Anna P

    2015-12-01

    This study was designed to determine whether 3 weeks of gabapentin treatment is effective in alleviating neuropathic pain-like behavior in animal models of complex regional pain syndrome type-I and partial sciatic nerve ligation (PSNL). We investigated the contribution of adenosine subtypes to the antihyperalgesic effect of gabapentin by examining the effect of caffeine, a non-selective adenosine A1 and A2 receptor antagonist or 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective adenosine A1 subtype receptor antagonist on this effect. Neuropathic pain was produced by unilateral prolonged hind paw ischemia and reperfusion (I/R) or PSNL procedures which resulted in stimulus-evoked mechanical hyperalgesia. After procedures, animals received gabapentin (10, 30, or 100 mg/kg intraperitoneal, respectively), caffeine (10 mg/kg intraperitoneal or 150 nmol intrathecally) or DPCPX (3 µg intrathecally) alone or in combination. Mice were tested for tactile mechanical hyperalgesia at 1, 2, and 3 weeks following procedures. Gabapentin produced dose-related inhibition of mechanical hyperalgesia over a 3-week period, and this effect was blocked by concomitant caffeine or DPCPX administration 1 week after injuries. The results of this study demonstrated that the mechanism through which gabapentin produces its effect may involve the activation of adenosine A1 subtype receptor.

  17. The proinflammatory RAGE/NF-κB pathway is involved in neuronal damage and reactive gliosis in a model of sleep apnea by intermittent hypoxia.

    Directory of Open Access Journals (Sweden)

    Maria Florencia Angelo

    Full Text Available Sleep apnea (SA causes long-lasting changes in neuronal circuitry, which persist even in patients successfully treated for the acute effects of the disease. Evidence obtained from the intermittent hypoxia (IH experimental model of SA has shown neuronal death, impairment in learning and memory and reactive gliosis that may account for cognitive and structural alterations observed in human patients. However, little is known about the mechanism controlling these deleterious effects that may be useful as therapeutic targets in SA. The Receptor for Advanced Glycation End products (RAGE and its downstream effector Nuclear Factor Kappa B (NF-κB have been related to neuronal death and astroglial conversion to the pro-inflammatory neurodegenerative phenotype. RAGE expression and its ligand S100B were shown to be increased in experimental models of SA. We here used dissociated mixed hippocampal cell cultures and male Wistar rats exposed to IH cycles and observed that NF-κB is activated in glial cells and neurons after IH. To disclose the relative contribution of the S100B/RAGE/NF-κB pathway to neuronal damage and reactive gliosis after IH we performed sequential loss of function studies using RAGE or S100B neutralizing antibodies, a herpes simplex virus (HSV-derived amplicon vector that induces the expression of RAGEΔcyto (dominant negative RAGE and a chemical blocker of NF-κB. Our results show that NF-κB activation peaks 3 days after IH exposure, and that RAGE or NF-κB blockage during this critical period significantly improves neuronal survival and reduces reactive gliosis. Both in vitro and in vivo, S100B blockage altered reactive gliosis but did not have significant effects on neuronal survival. We conclude that both RAGE and downstream NF-κB signaling are centrally involved in the neuronal alterations found in SA models, and that blockage of these pathways is a tempting strategy for preventing neuronal degeneration and reactive gliosis in SA.

  18. Eye Involvement in TSC

    Science.gov (United States)

    ... Privacy Policy Sitemap Learn Engage Donate About TSC Eyes Campbell (1905) first described the eye involvement in ... some form of eye involvement. Nonretinal and Retinal Eye Findings Facial angiofibromas may involve the eyelids of ...

  19. Involvement of Interleukin-10 in the Anti-Inflammatory Effect of Sanyinjiao (SP6 Acupuncture in a Mouse Model of Peritonitis

    Directory of Open Access Journals (Sweden)

    Morgana Duarte da Silva

    2011-01-01

    Full Text Available In this study, we determined the anti-inflammatory effect of manual acupuncture at the Sanyinjiao or Spleen 6 (SP6 point on carrageenan-induced peritonitis in mice and investigated mechanisms that may underlie this effect. In the first set of experiments, male Swiss mice were allocated into five groups: the control (sterile saline, dexamethasone (DEXA, invasive sham-acupuncture (non-acupoint, SP6 acupuncture and carrageenan-treated groups. Ten minutes after needle retention or 30 min after DEXA treatment, mice received an intraperitoneal injection of carrageenan (750 μg/mouse. After 4 h, total leukocyte and differential cell counts (neutrophils and mononuclear, myeloperoxidase (MPO activity, vascular permeability and cytokine levels were evaluated. In another set of experiments, adrenalectomized (ADX mice were used to study the involvement of the adrenal gland on the therapeutic effects of acupuncture. Mice were allocated into two groups: the ADX and sham-operated animals (Sham ADX that were subdivided into four subgroups each: the control (sterile saline, DEXA, SP6 acupuncture and carrageenan-treated groups. The SP6 and DEXA treatments inhibited the inflammatory cell infiltration, vascular permeability and MPO activity in carrageenan-injected mice. In addition, the SP6 treatment also increased interleukin (IL-10 levels. In contrast, when the animals were adrenalectomized, the SP6 treatment failed to reduce total leukocyte and the plasma extravasation. In conclusion, this study clearly demonstrates the anti-inflammatory effect of SP6 acupuncture in a model of carrageenan-induced peritonitis. Our results demonstrated that SP6 acupuncture depends of the adrenal glands and increased IL-10 levels to produce its anti-inflammatory action.

  20. Transcriptome profiling of gene expression during immunisation trial against Fasciola hepatica: identification of genes and pathways involved in conferring immunoprotection in a murine model.

    Science.gov (United States)

    Rojas-Caraballo, Jose; López-Abán, Julio; Moreno-Pérez, Darwin Andrés; Vicente, Belén; Fernández-Soto, Pedro; Del Olmo, Esther; Patarroyo, Manuel Alfonso; Muro, Antonio

    2017-01-23

    Fasciolosis remains a significant food-borne trematode disease causing high morbidity around the world and affecting grazing animals and humans. A deeper understanding concerning the molecular mechanisms by which Fasciola hepatica infection occurs, as well as the molecular basis involved in acquiring protection is extremely important when designing and selecting new vaccine candidates. The present study provides a first report of microarray-based technology for describing changes in the splenic gene expression profile for mice immunised with a highly effective, protection-inducing, multi-epitope, subunit-based, chemically-synthesised vaccine candidate against F. hepatica. The mice were immunised with synthetic peptides containing B- and T-cell epitopes, which are derived from F. hepatica cathepsin B and amoebapore proteins, as novel vaccine candidates against F. hepatica formulated in an adjuvant adaptation vaccination system; they were experimentally challenged with F. hepatica metacercariae. Spleen RNA from mice immunised with the highest protection-inducing synthetic peptides was isolated, amplified and labelled using Affymetrix standardised protocols. Data was then background corrected, normalised and the expression signal was calculated. The Ingenuity Pathway Analysis tool was then used for analysing differentially expressed gene identifiers for annotating bio-functions and constructing and visualising molecular interaction networks. Mice immunised with a combination of three peptides containing T-cell epitopes induced high protection against experimental challenge according to survival rates and hepatic damage scores. It also induced differential expression of 820 genes, 168 genes being up-regulated and 652 genes being down-regulated, p value hepatica in a murine model, which could be useful for evaluating future vaccine candidates.

  1. Who and What Does Involvement Involve?

    DEFF Research Database (Denmark)

    Hansen, Jeppe Oute; Petersen, Anders; Huniche, Lotte

    2015-01-01

    elucidates how a psycho-ideological discourse positions the mentally ill person as weak, incapable, and ineffective. By contrast, the supporting relative is positioned as a strong, capable, and effective co-therapist. Furthermore, the analysis considers how this dominant discourse of involvement...... theoretical perspective laid out by Ernesto Laclau and Chantal Mouffe, the aim of this study is to show how the dominant discourse about involvement at the political and clinical sites is constituted by understandings of mentally ill individuals and by political objectives of involvement. The analysis...... the responsibility toward the mental health of the ill individual as well as toward the psychological milieu of the family....

  2. GOVERNMENT INVOLVEMENT IN CONSUMPTION BEHAVIOUR

    Directory of Open Access Journals (Sweden)

    CRISTINA ZAMFIR

    2010-01-01

    Full Text Available In this article, we will follow the involvement that the government has,through its expenses, on the consumption behavior. The involvement that the government has inthe consumption behavior is made through fees and taxes that are applied on income. Fees andtaxes are applied to the different forms of income but in this article we will be focused only onthe influence of them on wages. In order to analyze the involvement of government expenses onconsumption behavior an utility model will be used.

  3. Expression of luxS gene involved in quorum sensing in Lactobacillus acidophilus NCFM after passage through an in vitro digestion model

    DEFF Research Database (Denmark)

    Moslehi Jenabian, Saloomeh; Jespersen, Lene

    sensing is cellto- cell signalling through the production, secretion and detection of small signal molecules called autoinducers. The aim of the present study was to investigate the transcription of the luxS gene involved in quorum sensing in probiotic strain Lactobacillus acidophilus NCFM after passage...

  4. Lung Involvement in TSC

    Science.gov (United States)

    ... Privacy Policy Sitemap Learn Engage Donate About TSC Lungs Lung involvement in tuberous sclerosis complex (TSC) has ... testing. (Krueger et al., 2013) What Are the Lung Features of TSC? Two forms of lung involvement ...

  5. The Effect of Job Involvement and Organizational Commitment on Employees\\\\\\' Job Satisfaction and Performance in Hotel Industry of Mashhad by Using Structural Equation Modeling

    Directory of Open Access Journals (Sweden)

    Hamed Derakhshide

    2014-05-01

    According to the results, every organization's most valuable asset is its human capital. This valuable capital have a direct impact on the failure or success of the organization. With hopes of developing a sense of commitment to its employees, every organization should have managers who are aware of the importance of this human capital, because individuals who are committed to the values and goals of the organization, play more active roles in the organization and are less likely to leave the organization. The results also indicate that affective commitment and normative commitment influence job satisfaction and job performance. Job involvement also influence affective commitment and normative commitment. Finally, job satisfaction and job performance are influenced by job involvement. By respecting employees' involvement in decision making and by using an appropriate incentive system, managers can increase their employees' commitment to the organization, and also improve job satisfaction and performance. Due to the high rate of mobility of workers in the hospitality industry, managers need new and diverse approaches to increase the commitment of their employees. In order to provide satisfaction and commitment to the needs of the employees, hotel management companies should be sufficiently sensitive.

  6. Comparative Town Meetings: A Search for Causative Models of Feminine Involvement in Politics with New Operational Definitions of a Well Calloused Dependent Variable.

    Science.gov (United States)

    Bryan, Frank M.

    Variations in the level of female political participation were examined in the context of the "standard" model of political participation (higher socioeconomic status, urbanism, living at society's center, increased participation) and the "decline of community" model (decreased group membership, increased mobility, decline of…

  7. Expression of luxS gene involved in quorum sensing in Lactobacillus acidophilus NCFM after passage through an in vitro digestion model

    DEFF Research Database (Denmark)

    Moslehi Jenabian, Saloomeh; Jespersen, Lene

    Within recent years, there has been an increasing interest in discovering the beneficial effects of probiotics and the mechanisms by which probiotics interact with the host and the gut microbiota. One of the mechanisms that bacteria interact or communicate with each other is quorum sensing. Quorum...... sensing is cellto- cell signalling through the production, secretion and detection of small signal molecules called autoinducers. The aim of the present study was to investigate the transcription of the luxS gene involved in quorum sensing in probiotic strain Lactobacillus acidophilus NCFM after passage...

  8. A murine experimental anthracycline extravasation model: pathology and study of the involvement of topoisomerase II alpha and iron in the mechanism of tissue damage

    DEFF Research Database (Denmark)

    Thougaard, Annemette V; Langer, Seppo W; Hainau, Bo;

    2010-01-01

    The bisdioxopiperazine topoisomerase II catalytic inhibitor dexrazoxane has successfully been introduced into the clinic as an antidote to accidental anthracycline extravasation based on our preclinical mouse studies. The histology of this mouse extravasation model was investigated and found...

  9. A Preclinical Model of Inflammatory Breast Cancer to Study the Involvement of CXCR4 and ACKR3 in the Metastatic Process

    OpenAIRE

    2015-01-01

    Inflammatory breast cancer (IBC) is an aggressive and invasive tumor, accounting for 2.5% of all breast cancer cases, and characterized by rapid progression, regional and distant metastases, younger age of onset, and lower overall survival. Presently, there are no effective therapies against IBC and a paucity of model systems. Our aim was to develop a clinically relevant IBC model that would allow investigations on the role of chemokine receptors in IBC metastasis. Primary cultures of tumor c...

  10. Facilitating interest and out-of-school engagement in science in secondary school girls: Increasing the effectiveness of the teaching for transformative experience in science model through parental involvement

    Science.gov (United States)

    Heddy, Benjamin Charles

    This study investigated the impact of adding a parental involvement intervention to the Teaching for Transformative Experience in Science (TTES) model in science courses (biology and chemistry) in an all-girl middle and high school (N = 89). Specifically, the goal was to increase out-of-school engagement, interest, parental involvement, and achievement. Analysis showed that TTES with the addition of a parent intervention (TTES+PI) facilitated more out-of-school engagement and parent involvement than a comparison. Furthermore, a high initial level of situational and individual interest was maintained in the TTES+PI condition; whereas both forms of interest decreased in the comparison. A content analysis of transformative experience journal entries suggested that when parents showed value for science concepts, students' experiential value increased. The results provide evidence that the addition of a parent intervention may increase the effectiveness of TTES and maintain girl's interest in science, which has theoretical and practical implications.

  11. Doctors' involvement in torture

    DEFF Research Database (Denmark)

    Sonntag, Jesper

    2008-01-01

    Doctors from both non-democratic and democratic countries are involved in torture. The majority of doctors involved in torture are doctors at risk. Doctors at risk might compromise their ethical duty towards patients for the following possible reasons: individual factors (such as career, economic...

  12. Optimal replenishment and credit policy in supply chain inventory model under two levels of trade credit with time- and credit-sensitive demand involving default risk

    Science.gov (United States)

    Mahata, Puspita; Mahata, Gour Chandra; Kumar De, Sujit

    2017-06-01

    Traditional supply chain inventory modes with trade credit usually only assumed that the up-stream suppliers offered the down-stream retailers a fixed credit period. However, in practice the retailers will also provide a credit period to customers to promote the market competition. In this paper, we formulate an optimal supply chain inventory model under two levels of trade credit policy with default risk consideration. Here, the demand is assumed to be credit-sensitive and increasing function of time. The major objective is to determine the retailer's optimal credit period and cycle time such that the total profit per unit time is maximized. The existence and uniqueness of the optimal solution to the presented model are examined, and an easy method is also shown to find the optimal inventory policies of the considered problem. Finally, numerical examples and sensitive analysis are presented to illustrate the developed model and to provide some managerial insights.

  13. A Descriptive and Explorative Case Study of a Scratch Programming Experience Involving the Creation of a Lunar Simulation/Model with Grade Six Learners

    Science.gov (United States)

    Martin, Stephen Alexander

    This mixed methods descriptive and exploratory case study examined the experiences of two classes in an elementary school (39 students) using the Scratch programming language to create a lunar simulation of the Earth/Moon System over six days. Using the Computational Thinking Framework developed by Brennan and Resnick (2012) the researcher examined the computational thinking (CT) concepts and practices students were exposed to. This study finds that all of the student groups experienced at least partial success in building their simulation. The researcher found that all of the groups explored the CT concepts of sequence, events, parallelism, conditionals and operators while building their simulation and more than 80% of the groups used data and loops. There is evidence that the students were involved in three of the computational practices: incremental and iterative, testing and debugging and, abstracting and modularizing. This study offers recommendations for practice and for future research.

  14. Citizen Involvement in Local Security Networks

    NARCIS (Netherlands)

    Terpstra, J.B.

    2009-01-01

    This paper deals with the involvement of citizens (and local businesspersons) in the prevention and control of crime and disorder. Four models of citizen involvement in local security networks are distinguished. In each of these models the role of citizens concentrates on different functions: (1) p

  15. Preventive Effect of TU-100 on a Type-2 Model of Colitis in Mice: Possible Involvement of Enhancing Adrenomedullin in Intestinal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Atsushi Kaneko

    2013-01-01

    Full Text Available Purpose. Crohn's disease (CD and ulcerative colitis (UC, the two major forms of inflammatory bowel disease (IBD, have histopathologically and immunologically different characteristics. We previously reported that a traditional Japanese medicine, daikenchuto (TU-100, ameliorated a trinitrobenzenesulfonic acid- (TNBS- induced type-1 model colitis exhibiting histopathological features of CD through adrenomedullin (ADM enhancement. Our current aims were to examine whether TU-100 ameliorates a type-2 model colitis that histologically resembles UC and identify the active ingredients. Methods. TU-100 was administered orally to mice with oxazolone- (OXN- induced type-2 model colitis. The morbidity was evaluated by body weight loss and the macroscopic score of colonic lesions. ADM was quantified using an EIA kit. Results. TU-100 prevented weight loss and colon ulceration. ADM production by intestinal epithelial cells was increased by TU-100 addition. Screening to identify active ingredients showed that [6]-shogaol and hydroxy α-sanshool enhanced ADM production. Conclusions. TU-100 exerted a protective effect in OXN-induced type-2 model colitis, indicating that TU-100 may be a beneficial agent for treatment of UC.

  16. The effect of childhood emotional maltreatment on romantic relationships in young adulthood: A double mediation model involving self-criticism and attachment.

    Science.gov (United States)

    Lassri, Dana; Luyten, Patrick; Cohen, Guina; Shahar, Golan

    2016-07-01

    Despite growing recognition of the importance of childhood emotional maltreatment (CEM) on the development of psychopathology, very few studies have addressed its impact on adult romantic relationship functioning, particularly among otherwise relatively well-functioning individuals. In an attempt to further elucidate the mechanism underlying the negative impact of CEM on romantic relationships, we tested an integrative mediational model linking CEM to romantic relationships through the impact of CEM on the development of self-criticism and adult attachment. Recent work in this context suggests that while self-criticism concerns broad cognitive-affective schemas related to achievement and failure, attachment avoidance assesses the expression of these broad schemas in close relationships (Luyten & Blatt, 2011; Sibley & Overall, 2008, 2010). This hypothesized mediational model was examined in a sample of young adult undergraduates (N = 99, 85 female), using structural equation modeling. The mediational model was in large part supported. Attachment avoidance, but not attachment anxiety, fully accounted for the mediating role of self-criticism in the relationship between CEM and romantic relationship satisfaction, even when controlling for the potential role of concurrent levels of posttraumatic stress disorder severity. Understanding the long-term psychological dynamics related to CEM and identifying mediating vulnerability factors-self-criticism and attachment avoidance-might have implications for both the assessment and treatment of individuals with a history of CEM, particularly as effective interventions to address self-criticism and attachment issues are available. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  17. Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1? expression

    Directory of Open Access Journals (Sweden)

    T. Wang

    2014-09-01

    Full Text Available Hypoxia-inducible factor-1α (HIF-1α is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each: sham-operated (group S, hindlimb ischemia-reperfusion (group IR, and ischemic postconditioning (group IPO. Each group was divided into subgroups (n=6 according to reperfusion time: immediate (0 h, T0, 1 h (T1, 3 h (T3, 6 h (T6, 12 h (T12, and 24 h (T24. In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T0-T24, serum creatine kinase (CK and lactate dehydrogenase (LDH activities, as well as interleukin (IL-6, IL-10, and tumor necrosis factor-α (TNF-α concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01. In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01, and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury-triggered inflammatory response.

  18. Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1α expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, T. [Department of Anesthesiology, Shuyang People' s Hospital, JiangSu (China); Zhou, Y.T. [Department of General Surgery, Shuyang People' s Hospital, JiangSu (China); Chen, X.N. [Institute of Pathophysiology, School of Basic Medical Sciences, LanZhou University, Lanzhou, Gansu (China); Zhu, A.X. [Department of Pharmacy, Shuyang People' s Hospital, JiangSu (China)

    2014-07-25

    Hypoxia-inducible factor-1α (HIF-1α) is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each): sham-operated (group S), hindlimb ischemia-reperfusion (group IR), and ischemic postconditioning (group IPO). Each group was divided into subgroups (n=6) according to reperfusion time: immediate (0 h, T{sub 0}), 1 h (T{sub 1}), 3 h (T{sub 3}), 6 h (T{sub 6}), 12 h (T{sub 12}), and 24 h (T{sub 24}). In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T{sub 0}-T{sub 24}), serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01). In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01), and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury

  19. Stress Corrosion Cracks Initiation Process Model Involving Repetition of Growth and Breaking of Oxide Passive Film or Hydride Layer on Stainless Alloy

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, G.; Sakakibara, Y. [Research Laboratory, IHI Corporation (Japan)

    2009-07-01

    The surface of stainless alloy is covered with oxide film such as Cr{sub 2}O{sub 3} and is passivated in neutral aqueous solution. This film attains a thickness that may be expressed in micro meter units({mu}m) and may undergo partial rupture physically in a high-temperature oxygen enriched water environment. Crack propagation occurs through repeated growth and rupture of the oxide film; the rupturing process is designated as tarnish rupture type SCC. Individual cracks are initiated randomly for film of uniform thickness and this process may be described by the stochastic model. Hydride layer formation occurs on the alloy surface under the proper conditions, using titanium in a reducing neutral water environment. Crack initiation may thus also be described by a model similar to that for film rupture. (authors)

  20. An Exploratory Model of the Relationships between Empowerment, Job Involvement, Job Satisfaction, Organizational Commitment, and Customer Orientation in the Hospitality Industry

    OpenAIRE

    Jun, Jaekyoon

    1998-01-01

    The concept of customer orientation is becoming increasingly more important to managers, especially in service industries. Given the premise of the study that a customer-oriented employee has a critical role in enhancing service quality, little research has investigated the antecedents of the customer orientation construct. The objective of this study was to develop a theoretical model of customer orientation, and to test the hypothesized relationships between customer orientation and its ant...

  1. LysM domains of Medicago truncatula NFP protein involved in Nod factor perception. Glycosylation state, molecular modeling and docking of chitooligosaccharides and Nod factors.

    Science.gov (United States)

    Mulder, Lonneke; Lefebvre, Benoit; Cullimore, Julie; Imberty, Anne

    2006-09-01

    The establishment of the symbiosis between legume plants and rhizobial bacteria depends on the production of rhizobial lipo-chitooligosaccharidic signals (the Nod factors) that are specifically recognized by roots of the host plant. In Medicago truncatula, specific recognition of Sinorhizobium meliloti and its Nod factors requires the NFP (Nod factor perception) gene, which encodes a putative serine/threonine receptor-like kinase (RLK). The extracellular region of this protein contains three tandem lysin motifs (LysMs), a short peptide domain that is implicated in peptidoglycan or chitin binding in various bacterial or eukaryotic proteins, respectively. We report here the homology modeling of the three LysM domains of M. truncatula NFP based on the structure of a LysM domain of the Escherichia coli membrane-bound lytic murein transglycosidase D (MltD). Expression of NFP in a homologous system (M. truncatula roots) revealed that the protein is highly N-glycosylated, probably with both high-mannose and complex glycans. Surface analysis and docking calculations performed on the models of the three domains were used to predict the most favored binding modes for chitooligosaccharides and Nod factors. A convergent model can be proposed where the sulfated, O-acetylated lipo-chitooligosaccharidic Nod factor of S. meliloti binds in similar orientation to the three LysM domains of M. truncatula NFP. N-glycosylation is not expected to interfere with Nod factor binding in this orientation.

  2. Numerical modelling of biophysicochemical effects on multispecies reactive transport in porous media involving Pseudomonas putida for potential microbial enhanced oil recovery application.

    Science.gov (United States)

    Sivasankar, P; Rajesh Kanna, A; Suresh Kumar, G; Gummadi, Sathyanarayana N

    2016-07-01

    pH and resident time of injected slug plays a critical role in characterizing the reservoir for potential microbial enhanced oil recovery (MEOR) application. To investigate MEOR processes, a multispecies (microbes-nutrients) reactive transport model in porous media was developed by coupling kinetic and transport model. The present work differs from earlier works by explicitly determining parametric values required for kinetic model by experimental investigations using Pseudomonas putida at different pH conditions and subsequently performing sensitivity analysis of pH, resident time and water saturation on concentrations of microbes, nutrients and biosurfactant within reservoir. The results suggest that nutrient utilization and biosurfactant production are found to be maximum at pH 8 and 7.5 respectively. It is also found that the sucrose and biosurfactant concentrations are highly sensitive to pH rather than reservoir microbial concentration, while at larger resident time and water saturation, the microbial and nutrient concentrations were lesser due to enhanced dispersion. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson’s disease: Involvement of mitochondrial dysfunctions and oxidative stress

    Science.gov (United States)

    Kumar, Sanjeev; Giri, Anirudha; Sandhir, Rajat

    2017-01-01

    Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer’s disease while its role in the occurrence of Parkinson’s disease (PD) is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents. However, the impact of hypercholesterolemia on the midbrain dopaminergic neurons in animal models of PD remains elusive. We tested the hypothesis that hypercholesterolemia in MPTP model of PD would potentiate dopaminergic neuron loss in SN by disrupting mitochondrial functions and antioxidant homeostasis. It is evident from the present study that hypercholesterolemia in naïve animals caused dopamine neuronal loss in SN with subsequent reduction in striatal dopamine levels producing motor impairment. Moreover, in the MPTP model of PD, hypercholesterolemia exacerbated MPTP-induced reduction of striatal dopamine as well as dopaminergic neurons in SN with motor behavioral depreciation. Activity of mitochondrial complexes, mainly complex-I and III, was impaired severely in the nigrostriatal pathway of hypercholesterolemic animals treated with MPTP. Hypercholesterolemia caused oxidative stress in the nigrostriatal pathway with increased generation of hydroxyl radicals and enhanced activity of antioxidant enzymes, which were further aggravated in the hypercholesterolemic mice with Parkinsonism. In conclusion, our findings provide evidence of increased vulnerability of the midbrain dopaminergic neurons in PD with hypercholesterolemia. PMID:28170429

  4. Anti-Depressant-Like Effect of Kaempferitrin Isolated from Justicia spicigera Schltdl (Acanthaceae in Two Behavior Models in Mice: Evidence for the Involvement of the Serotonergic System

    Directory of Open Access Journals (Sweden)

    Julia Cassani

    2014-12-01

    Full Text Available We evaluated the antidepressant-like effect of kaempferitrin (Km isolated from the plant Justicia spicigera (Asteraceae, which is used in traditional medicine for relieving emotional disorders, such as “la tristeza” (sadness or dysthymia and “el humor” (mood changes. The actions of Km were evaluated in a forced swimming test (FST and a suspension tail test (TST in mice. We explored the involvement of the serotonergic system and the hypothalamic-hypophysis-adrenal axis (HPA in the antidepressant-like effect of Km. To evaluate nonspecific effects of Km on general activity, the open field test (OFT was performed. Km at 5, 10, and 20 mg/kg induced an antidepressant-like effect. Sub-effective dose of Km (1 mg/kg produced a synergistic effect with imipramine (6.25 mg/kg and fluoxetine (10 mg/kg but not with desipramine (3.12 mg/kg. Pretreatment with p-chlorophenylalanine methyl ester (PCPA, a serotonin synthesis inhibitor, N-{2-(4-(2-methoxyphenyl-1-piperazinyl}-N-(2-pyridinylcyclohexecarboxamide (WAY-100635, a selective 5-HT1A receptor antagonist, and 8OH-DPAT, a selective 5-HT1A agonist, but not pindolol (10 mg/kg blocked the anti- immobility effect induced by Km. Taken together, these results indicate that the antidepressant-like effect of Km is related to the serotonergic system, principally 5-HT1A. This effect was not related to changes in locomotor activity.

  5. Anti-depressant-like effect of kaempferitrin isolated from Justicia spicigera Schltdl (Acanthaceae) in two behavior models in mice: evidence for the involvement of the serotonergic system.

    Science.gov (United States)

    Cassani, Julia; Dorantes-Barrón, Ana María; Novales, Lilian Mayagoitia; Real, Guadalupe Alva; Estrada-Reyes, Rosa

    2014-12-19

    We evaluated the antidepressant-like effect of kaempferitrin (Km) isolated from the plant Justicia spicigera (Asteraceae), which is used in traditional medicine for relieving emotional disorders, such as "la tristeza" (sadness or dysthymia) and "el humor" (mood changes). The actions of Km were evaluated in a forced swimming test (FST) and a suspension tail test (TST) in mice. We explored the involvement of the serotonergic system and the hypothalamic-hypophysis-adrenal axis (HPA) in the antidepressant-like effect of Km. To evaluate nonspecific effects of Km on general activity, the open field test (OFT) was performed. Km at 5, 10, and 20 mg/kg induced an antidepressant-like effect. Sub-effective dose of Km (1 mg/kg) produced a synergistic effect with imipramine (6.25 mg/kg) and fluoxetine (10 mg/kg) but not with desipramine (3.12 mg/kg). Pretreatment with p-chlorophenylalanine methyl ester (PCPA), a serotonin synthesis inhibitor, N-{2-(4-(2-methoxyphenyl)-1-piperazinyl}-N-(2-pyridinyl)cyclohexecarboxamide (WAY-100635), a selective 5-HT1A receptor antagonist, and 8OH-DPAT, a selective 5-HT1A agonist, but not pindolol (10 mg/kg) blocked the anti- immobility effect induced by Km. Taken together, these results indicate that the antidepressant-like effect of Km is related to the serotonergic system, principally 5-HT1A. This effect was not related to changes in locomotor activity.

  6. GTSE1: a novel TEAD4-E2F1 target gene involved in cell protrusions formation in triple-negative breast cancer cell models

    Science.gov (United States)

    Stelitano, Debora; Leticia, Yamila Peche; Dalla, Emiliano; Monte, Martin; Piazza, Silvano; Schneider, Claudio

    2017-01-01

    GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies, including breast cancer. Despite this, the transcriptional regulation of this protein and the causes of its misregulation in tumors remain largely unknown. The aims of this work were to elucidate how GTSE1 is regulated at the transcriptional level and to clarify the mechanism underlying GTSE1-dependent cell functions in triple-negative breast cancer (TNBC). Here, we identified GTSE1 as a novel target gene of the TEAD4 transcription factor, highlighting a role for the YAP and TAZ coactivators in the transcriptional regulation of GTSE1. Moreover, we found that TEAD4 controls the formation of cell protrusions required for cell migration through GTSE1, unveiling a relevant effector role for this protein in the TEAD-dependent cellular functions and confirming TEAD4 role in promoting invasion and metastasis in breast cancer. Finally, we highlighted a role for the pRb-E2F1 pathway in the control of GTSE1 transcription and observed that treatment with drugs targeting the pRb-E2F1 or YAP/TAZ-TEAD pathways dramatically downregulated the expression levels of GTSE1 and of other genes involved in the formation of metastasis, suggesting their potential use in the treatment of TNBC.

  7. Determination of molecular groups involved in the interaction of annexin A5 with lipid membrane models at the air-water interface.

    Science.gov (United States)

    Fezoua-Boubegtiten, Zahia; Desbat, Bernard; Brisson, Alain; Lecomte, Sophie

    2010-06-01

    Annexin A5 (AnxA5) is a member of a family of homologous proteins sharing the ability to bind to negatively charged phospholipid membranes in a Ca(2+)-dependent manner. In this paper, we used polarization-modulated infrared reflection absorption spectroscopy (PMIRRAS), Brewster angle microscopy (BAM), and ellipsometry to investigate changes both in the structure of AnxA5 and phospholipid head groups associated with membrane binding. We found that the secondary structure of AnxA5 in the AnxA5/Ca(2+)/lipid ternary complex is conserved, mainly in alpha-helices and the average orientation of the alpha-helices of the protein is slightly tilted with respect to the normal to the phospholipid monolayer. Upon interaction between AnxA5 and phospholipids, a shift of the nu(as) PO(2)(-) band is observed by PMIRRAS. This reveals that the phosphate group is the main group involved in the binding of AnxA5 to phospholipids via Ca(2+) ions, even when some carboxylate groups are accessible (PS). PMIRRAS spectra also indicate a change of carboxylate orientation in the aspartate and glutamate residues implicated in the association of the AnxA5, which could be linked to the 2D crystallization of protein under the phospholipid monolayer. Finally, we demonstrated that the interaction of AnxA5 with pure carboxylate groups of an oleic acid monolayer is possible, but the orientation of the protein under the lipid is completely different.

  8. Consumer Involvement in Rehabilitation

    Science.gov (United States)

    Daniels, Susan

    1976-01-01

    With the emphasis on consumer involvement in the Rehabilitation Act of 1973, changes in the counseling relationship must occur. This article discusses new interaction patterns for consumer and counselor. (Author)

  9. Clinical studies involving probiotics

    OpenAIRE

    Degnan, Fred H

    2012-01-01

    Researchers from a diverse array of scientific disciplines have focused and continue to focus on opportunities and areas for responsible clinical research involving the possible beneficial health effects of “probiotics.” Investigators and researchers should be aware that not all clinical research involving probiotics reasonably falls within the requirements of the “investigational new drug” (IND) rubric administered and enforced by the US Food and Drug Administration. In determining whether a...

  10. Impact of vasculature damage on the outcome of spinal cord injury:a novel collagenase-induced model may give new insights into the mechanisms involved

    Institute of Scientific and Technical Information of China (English)

    Patrick Losey; Daniel C. Anthony

    2014-01-01

    The deleterious effect of vasculature damage on the outcome of spinal cord injury has long been recognized, and numerous clinical studies have shown that the presence of hemorrhage into the spinal cord is directly associated with a poorer neurological outcome. Vascular damage leads to de-creased blood lfow to the cord and the release of potentially toxic blood-borne components. Here we consider the mechanisms that may be contributing to hemorrhage-induced damage and discuss the utility of a new model of spinal cord hemorrhage, which was urgently required as most of our current understanding has been extrapolated from intracerebral hemorrhage studies.

  11. Motor cortex-periaqueductal gray-spinal cord neuronal circuitry may involve in modulation of nociception: a virally mediated transsynaptic tracing study in spinally transected transgenic mouse model.

    Directory of Open Access Journals (Sweden)

    Da-Wei Ye

    Full Text Available Several studies have shown that motor cortex stimulation provided pain relief by motor cortex plasticity and activating descending inhibitory pain control systems. Recent evidence indicated that the melanocortin-4 receptor (MC4R in the periaqueductal gray played an important role in neuropathic pain. This study was designed to assess whether MC4R signaling existed in motor cortex-periaqueductal gray-spinal cord neuronal circuitry modulated the activity of sympathetic pathway by a virally mediated transsynaptic tracing study. Pseudorabies virus (PRV-614 was injected into the left gastrocnemius muscle in adult male MC4R-green fluorescent protein (GFP transgenic mice (n = 15. After a survival time of 4-6 days, the mice (n = 5 were randomly assigned to humanely sacrifice, and spinal cords and brains were removed and sectioned, and processed for PRV-614 visualization. Neurons involved in the efferent control of the left gastrocnemius muscle were identified following visualization of PRV-614 retrograde tracing. The neurochemical phenotype of MC4R-GFP-positive neurons was identified using fluorescence immunocytochemical labeling. PRV-614/MC4R-GFP dual labeled neurons were detected in spinal IML, periaqueductal gray and motor cortex. Our findings support the hypothesis that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may participate in the modulation of the melanocortin-sympathetic signaling and contribute to the descending modulation of nociceptive transmission, suggesting that MC4R signaling in motor cortex-periaqueductal gray-spinal cord neural pathway may modulate the activity of sympathetic outflow sensitive to nociceptive signals.

  12. Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

    Energy Technology Data Exchange (ETDEWEB)

    Kalayarasan, Srinivasan, E-mail: kalaivasanbio@gmail.com; Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam, E-mail: sudhandiran@yahoo.com

    2013-09-01

    Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, α-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells.

  13. Anticonvulsant effect of Rhynchophylline involved in the inhibition of persistent sodium current and NMDA receptor current in the pilocarpine rat model of temporal lobe epilepsy.

    Science.gov (United States)

    Shao, Hui; Yang, Yang; Mi, Ze; Zhu, Guang-Xi; Qi, Ai-Ping; Ji, Wei-Gang; Zhu, Zhi-Ru

    2016-11-19

    Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. Several studies have demonstrated that RIN has a significant anticonvulsant effect in many types of epilepsy models in vivo. However, the mechanisms of the anticonvulsant effect remain elusive. Using combined methods of behavioral testing, immunofluorescence and electrophysiological recordings, we characterized the anticonvulsant effect of RIN in a pilocarpine-induced status epilepticus (SE) rat model of temporal lobe epilepsy (TLE) and investigated the underlying cellular mechanisms. In one set of experiments, rats received RIN treatment prior to pilocarpine injection. In a second set of experiments, rats received RIN treatment following the onset of stage 3 seizures. Pretreatment and posttreatment with RIN effectively reduced the seizure severity in the acute phase of TLE. Furthermore, RIN protected medial entorhinal cortex (mEC) layer III neurons from neuronal death and terminated spontaneous epileptiform discharge of mEC layer II neurons in SE-experienced rats. Whole-cell voltage-clamp recordings indicated that RIN inhibited neuronal hyperexcitability via inhibition of the persistent sodium current (INaP) and NMDA receptor current. Immunofluorescence experiments also demonstrated that RIN rectified the pilocarpine-induced upregulation of Nav1.6 and NR2B protein expression. In conclusion, our results identified RIN as an anticonvulsant agent that inhibited ictal discharge via INap and NMDA receptor current inhibition.

  14. Modeling the effects of involvement and attitudes on energy industry pursuit intentions: A systems analysis of the university-industry environment

    Science.gov (United States)

    Gross, Jordan M.

    The energy industry's struggle to attract and retain qualified employees continues to threaten the nation's economy, global competitiveness, and national security. Given the nationwide skills and labor shortage in the energy industry, this study was conducted in response to a need to identify causes of person-environment fit and its effects on engineering students' intentions to work in the energy industry after graduation. Structural equation modeling was used to examine the relationships between student inputs, environmental factors, and career-related outcomes. Two models were compared using data collected from 381 undergraduate engineering students from across the country. Results suggest that students who gained knowledge about professions in the energy industry from participating in an internship or co-op at an energy-related company perceived greater fit with the goals and values of the energy industry. In addition, this study found that students who perceive high levels of fit with the energy industry also have high industry attraction, which directly affects their energy industry pursuit intentions. Overall, this research indicates that high quality internships have the potential to increase students' perceived industry fit, which is closely tied to their career intentions. Outcomes of this study are expected to provide stakeholders with new insights to improve practices within the university-industry environment that will educate, promote, and sustain a strong energy workforce for years to come.

  15. Short Communication: Is Ethanol-Based Hand Sanitizer Involved in Acute Pancreatitis after Excessive Disinfection?—An Evaluation with the Use of PBPK Model

    Directory of Open Access Journals (Sweden)

    Céline Huynh-Delerme

    2012-01-01

    Full Text Available An occupational physician reported to the French Health Products Safety Agency (Afssaps a case of adverse effect of acute pancreatitis (AP in a teaching nurse, after multiple demonstrations with ethanol-based hand sanitizers (EBHSs used in a classroom with defective mechanical ventilation. It was suggested by the occupational physician that the exposure to ethanol may have produced a significant blood ethanol concentration and subsequently the AP. In order to verify if the confinement situation due to defective mechanical ventilation could increase the systemic exposure to ethanol via inhalation route, a physiologically based pharmacokinetic (PBPK modeling was used to predict ethanol blood levels. Under the worst case scenario, the simulation by PBPK modeling showed that the maximum blood ethanol concentration which can be predicted of 5.9 mg/l is of the same order of magnitude to endogenous ethanol concentration (mean = 1.1 mg/L; median = 0.4 mg/L; range = 0–35 mg/L in nondrinker humans (Al-Awadhi et al., 2004. The present study does not support the likelihood that EBHS leads to an increase in systemic ethanol concentration high enough to provoke an acute pancreatitis.

  16. HiRISE observations of gas sublimation-driven activity in Mars' southern polar regions: III. Models of processes involving translucent ice

    Science.gov (United States)

    Portyankina, G.; Markiewicz, W.J.; Thomas, N.; Hansen, C.J.; Milazzo, M.

    2010-01-01

    Enigmatic surface features, known as 'spiders', found at high southern martian latitudes, are probably caused by sublimation-driven erosion under the seasonal carbon dioxide ice cap. The Mars Reconnaissance Orbiter (MRO) High Resolution Imaging Science Experiment (HiRISE) has imaged this terrain in unprecedented details throughout southern spring. It has been postulated [Kieffer, H.H., Titus, T.N., Mullins, K.F., Christensen, P.R., 2000. J. Geophys. Res. 105, 9653-9700] that translucent CO2 slab ice traps gas sublimating at the ice surface boundary. Wherever the pressure is released the escaping gas jet entrains loose surface material and carries it to the top of the ice where it is carried downslope and/or downwind and deposited in a fan shape. Here we model two stages of this scenario: first, the cleaning of CO2 slab ice from dust, and then, the breaking of the slab ice plate under the pressure built below it by subliming ice. Our modeling results and analysis of HiRISE images support the gas jet hypothesis and show that outbursts happen very early in spring. ?? 2009 Elsevier Inc. All rights reserved.

  17. Enhancement of β-amyloid oligomer accumulation after intracerebroventricular injection of streptozotocin, which involves central insulin signaling in a transgenic mouse model.

    Science.gov (United States)

    Lin, Fangju; Jia, Jianping; Qin, Wei

    2014-11-12

    The β-amyloid (Aβ) oligomer rather than fibrillar Aβ has become the important focus of recent studies on the pathogenesis of Alzheimer's disease (AD). Insulin signaling plays important roles in cognitive disease, such as AD. However, in-vivo evidence for the link between central insulin signaling and the Aβ oligomer are lacking, and the mechanisms underlying the effect of central insulin signaling on AD are still elusive. Our team has established the Presenilin-1 Val97Leu mutant transgenic (PS1V97L) AD mouse model with the intraneuronal Aβ oligomer as the potential initiator for other pathologies, but without extracellular amyloid plaque formation. Using this model, we investigated the roles of disturbed central insulin signaling induced by intracerebroventricular injection of streptozotocin (STZ) in the progression of AD. We observed that PS1V97L mice after intracerebroventricular injection of STZ showed increased Aβ oligomer accumulation and aggravated spatial learning and memory deficit in the absence of diabetes symptoms. Furthermore, STZ administration inhibited the activation of the insulin receptor and enhanced the activation of c-Jun NH2-terminal kinase, which was accompanied by increased production of carboxy-terminal fragments from the amyloid precursor protein, in the brain of PS1V97L mice. Overall, our study provided in-vivo evidence for a role of central insulin signaling in AD progression.

  18. On the Involvement of Copper Binding to the N-Terminus of the Amyloid Beta Peptide of Alzheimer's Disease: A Computational Study on Model Systems

    Directory of Open Access Journals (Sweden)

    Samira Azimi

    2011-01-01

    Full Text Available Density functional and second order Moller-Plesset perturbation theoretical methods, coupled with a polarizable continuum model of water, were applied to determine the structures, binding affinities, and reduction potentials of Cu(II and Cu(I bound to models of the Asp1, Ala2, His6, and His13His14 regions of the amyloid beta peptide of Alzheimer's disease. The results indicate that the N-terminal Asp binds to Cu(II together with His6 and either His13 or His14 to form the lower pH Component I of Aβ. Component II of Aβ is the complex between Cu(II and His6, His13, and His14, to which an amide O (of Ala2 is also coordinated. Asp1 does not bind to Cu(II if three His residues are attached nor to any Cu(I species to which one or more His residues are bound. The most stable Cu(I species is one in which Cu(I bridges the Nδ of His13 and His14 in a linear fashion. Cu(I binds more strongly to Aβ than does Cu(II. The computed reduction potential that closely matches the experimental value for Cu(II/Aβ corresponds to reduction of Component II (without Ala2 to the Cu(I complex after endergonic attachment of His6.

  19. Modeling the interfacial interactions between CrtS and CrtR from Xanthophyllomyces dendrorhous , a P450 system involved in astaxanthin production.

    Science.gov (United States)

    Alcaíno, Jennifer; Fuentealba, Matías; Cabrera, Ricardo; Baeza, Marcelo; Cifuentes, Víctor

    2012-09-05

    Xanthophyllomyces dendrorhous is a natural source of astaxanthin, a carotenoid widely used in the food industry. In this yeast, astaxanthin is synthesized from β-carotene by a cytochrome P450, CrtS, which depends on CrtR, the four-domain cytochrome P450 reductase (CPR). Although Saccharomyces cerevisiae has an endogenous CPR (ScCPR), expression of CrtS does not result in astaxanthin production unless it is coexpressed with CrtR. Assuming that CrtS could interact with the FMN-binding domain of either CrtR or ScCPR (XdFMNbd and ScFMNbd, respectively), the aim of this work was to identify possible interaction differences between these alternative complexes by protein modeling and short molecular dynamics simulations. Considering the recently proposed membrane orientation of a mammalian P450, our CrtS-CrtR model predicts that both N-terminal ends stand adjacent to the membrane plane, allowing their anchoring. Compared with the possible interface between CrtS and both FMNbd, the Xanthophyllomyces system appears to be stabilized by more saline bridges.

  20. Pancreatic Involvement in Melioidosis

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    Vui Heng Chong

    2010-07-01

    Full Text Available Context Melioidosis is endemic to tropical regions and, despite the common occurrence of intra-abdominal abscesses, pancreatic involvement in melioidosis has not previously been reported. Objective We report our experience with pancreatic melioidosis. Patients All 65 patients treated for melioidosis who had computed tomography (CT scans were identified from prospective databases and were retrospectively reviewed. Main outcome measures A detailed review of cases with pancreas involvement was carried out. Results There were four cases (three males and one female; median age 29.5 years, range: 25-48 years with pancreatic melioidosis, giving a prevalence of 6.2%. All had predisposing conditions (two had poorly controlled diabetes mellitus and two had thalassemia for melioidosis. Fever (100%, anorexia (100%, weight loss (100%, rigor (75% and abdominal pain (75% were the most common symptoms at presentation and the median duration of symptoms before presentation was six weeks (range: 2-8 weeks. All pancreatic abscesses were detected on CT scan. Multiple foci involvement was common (3 to 6 sites: blood (4 patients, liver (3 patients, psoas muscle (2 patients, spleen (2 patients, infected ascites (2 patients and lung (1 patient. Pancreatic involvement ranged from multi-focal micro-abscesses to focal large abscesses and involved all parts of the pancreas (body 100%, head 75% and tail 50%. Associated pancreatic findings included splenic vein thrombosis, peripancreatic inflammation and peripancreatic fat streaking. All the pancreatic abscesses were resolved with antibiotics without requiring pancreatic abscess drainage (including one patient who died from disseminated melioidosis. Conclusion Pancreatic involvement typically occurs as part of multi-organ involvement and commonly manifests as multifoci micro-abscesses. Associated pancreatic abnormalities were also common. All responded to treatment without requiring drainage

  1. Th17 cell-mediated neuroinflammation is involved in neurodegeneration of aβ1-42-induced Alzheimer's disease model rats.

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    Jun Zhang

    Full Text Available Neuroinflammation, especially innate immunocyte-mediated neuroinflammation, has been reported to participate in pathogenesis of Alzheimer's disease (AD. However, the involvement of adaptive immune cells, such as CD4(+ T lymphocytes, in pathogenesis of AD is not well clarified. Herein, we focus on T helper 17 (Th17 cells, a subpopulation of CD4(+ T cells with high proinflammation, and show the implication of the cells in neurodegeneration of AD. Amyloid β1-42 (Aβ1-42 was bilaterally injected into hippocampus of rats to induce AD. On days 7 and 14 following the Aβ1-42 administration, escape latency of the rats in Morris water maze was increased, expression of amyloid precursor protein was upregulated, but expression of protein phosphatase 2A was downregulated in the hippocampus, and Nissl stain showed neuronal loss and gliosis in CA1 region. Infusion of FITC-linked albumin in blood circulation and combination with immunostaining of hippocampal sections for RORγ, a specific transcriptional factor of Th17 cells, demonstrated blood-brain barrier (BBB disruption and Th17 cells' infiltration into brain parenchyma of AD rats. Expression of Th17 proinflammatory cytokines, interleukin (IL-17 and IL-22, was increased in the hippocampus, and concentrations of the two cytokines were elevated in both the cerebrospinal fluid and the serum in AD occurrence and development. Compared with intact or saline-treated control rats, AD animals indicated an upregulated expression of Fas and FasL in the hippocampus. Further, the immunofluorescent histochemistry on AD hippocampal sections with NeuN, RORγ, Fas and FasL displayed that Fas was principally expressed by neurons and FasL was predominantly expressed by Th17 cells, and that neuronal apoptosis shown by TUNEL and NeuN double-labeled cells increased. These results suggest that Th17 cells, which were infiltrated into AD brain parenchyma, participate in neuroinflammation and neurodegeneration of AD by release of

  2. Th17 cell-mediated neuroinflammation is involved in neurodegeneration of aβ1-42-induced Alzheimer's disease model rats.

    Science.gov (United States)

    Zhang, Jun; Ke, Kai-Fu; Liu, Zhan; Qiu, Yi-Hua; Peng, Yu-Ping

    2013-01-01

    Neuroinflammation, especially innate immunocyte-mediated neuroinflammation, has been reported to participate in pathogenesis of Alzheimer's disease (AD). However, the involvement of adaptive immune cells, such as CD4(+) T lymphocytes, in pathogenesis of AD is not well clarified. Herein, we focus on T helper 17 (Th17) cells, a subpopulation of CD4(+) T cells with high proinflammation, and show the implication of the cells in neurodegeneration of AD. Amyloid β1-42 (Aβ1-42) was bilaterally injected into hippocampus of rats to induce AD. On days 7 and 14 following the Aβ1-42 administration, escape latency of the rats in Morris water maze was increased, expression of amyloid precursor protein was upregulated, but expression of protein phosphatase 2A was downregulated in the hippocampus, and Nissl stain showed neuronal loss and gliosis in CA1 region. Infusion of FITC-linked albumin in blood circulation and combination with immunostaining of hippocampal sections for RORγ, a specific transcriptional factor of Th17 cells, demonstrated blood-brain barrier (BBB) disruption and Th17 cells' infiltration into brain parenchyma of AD rats. Expression of Th17 proinflammatory cytokines, interleukin (IL)-17 and IL-22, was increased in the hippocampus, and concentrations of the two cytokines were elevated in both the cerebrospinal fluid and the serum in AD occurrence and development. Compared with intact or saline-treated control rats, AD animals indicated an upregulated expression of Fas and FasL in the hippocampus. Further, the immunofluorescent histochemistry on AD hippocampal sections with NeuN, RORγ, Fas and FasL displayed that Fas was principally expressed by neurons and FasL was predominantly expressed by Th17 cells, and that neuronal apoptosis shown by TUNEL and NeuN double-labeled cells increased. These results suggest that Th17 cells, which were infiltrated into AD brain parenchyma, participate in neuroinflammation and neurodegeneration of AD by release of

  3. Evaluation of the therapeutic efficacy of sequential therapy involving percutaneous microwave ablation in combination with 131I-hypericin using the VX2 rabbit breast solid tumor model.

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    Miao Zhu

    Full Text Available Combination of percutaneous microwave ablation (PMWA and intravenous injection of 131I-hypericin(IIIH may bear potential as a mini-invasive treatment for tumor. The objective of this study was to assess the effect of PMWA and IIIH in breast tumor growth.Ten New Zealand White rabbits bearing VX2 breast carcinomas were randomly divided into two groups (each 5 examples and processed using PMWA followed by IIIH and IIIH alone. The IIIH activity was evaluated using planar scintigraphy, autoradiography and biodistribution analysis. The maximum effective safe dose of IIIH was found through 48 rabbits with VX2 breast tumor, which were randomized into six groups (n=8 per group. Subsequently, a further 75 rabbits bearing VX2 breast solid tumors were randomly divided into five groups (each 15 examples and treated as follows: A, no treatment group; B, PMWA alone; C, IIIH alone; D, PMWA+IIIH×1 (at 8 h post-PMWA; and E, PMWA+IIIH×2 (at 8 h and at 8 days post-PMWA. The therapeutic effect was assessed by measurement of tumor size and performation of positron emission tomography/computed tomograph (PET/CT scans, liver and renal function tests and Kaplan-Meier survival analysis.The planar scintigraphy findings suggested a significant uptake of 131I in necrotic tumor tissue. The autoradiography gray scales indicated higher selective uptake of IIIH by necrotic tissue, with significant differences between the groups with and those without necrotic tumor tissue (P<0.05. The maximum effective safe dose of IIIH was 1 mCi/kg. The PET/CT scans and tumor size measurement suggested improvements in treatment groups at all time points (P<0.01. Significant differences were detected among Groups A, B, D and E (P<0.05. Lower levels of lung metastasis were detected in Groups D and E (P<0.05. There were no abnormalities in liver and renal functions tests or other reported side effects.IIIH exhibited selective uptake by necrotic tumor tissue. Sequential therapy involving PMWA

  4. Lithium attenuates cannabinoid-induced dependence in the animal model: involvement of phosphorylated ERK1/2 and GSK-3β signaling pathways.

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    Hamid Reza Rahimi

    2014-09-01

    Full Text Available Cannabis is one of the most banned drugs in the world. Cannabinoid-induced dependence or withdrawal signs are indicated by the result of complex molecular mechanisms including upstream protein kinases (PKs, such as an extracellular signal regulated kinase1/2 (ERK1/2 and downstream glycogen synthase kinase-3β (GSK-3β, which lead to neuronal plasticity. In this study, we examined the protective effect of lithium (Li as a potent ERK1/2 and GSK-3β modulator to prevent the development of dependence on cannabinoids. For this purpose, rats were treated twice daily with increasing doses of WIN 55,212-2 (WIN, 2-8 mg/kg, intraperitoneally (i.p., for five consecutive days. AM251 (AM, 2 mg/kg, a cannabinoid antagonist, was injected i.p to induce manifestations of abstinence in rat dependency on WIN, and the subsequent withdrawal signs were recorded. To evaluate the preventive effect of Li, the rats were pre-treated with Li (10 mg/kg, i.p. twice daily, 30 minutes before every injection of WIN. SL327, as an ERK1/2 inhibitor, was also injected (SL, 50 mg/kg, i.p. 30 minutes before the last doses of WIN in separate groups. The p-ERK1/2, total ERK1/2, p-GSK-3β and total GSK-3β expressions were determined with Western blot method after 60 minutes, prior to the Li, WIN or AM injections. Li and SL pre-treatment attenuated the global withdrawal signs in regarding their modulation effect on the up-regulation of p-ERK1/2 cascade enhanced by AM injection. Furthermore, the p-GSK-3β expression was up-regulated with SL and Li pre-treatment against AM injection, without alteration on the total contents of ERK1/2 and GSK-3β level. Therefore, p-ERK1/2 and p-GSK-3β pathways are involved in the cannabinoid-induced dependence. However, no crosstalk was indicated between these two pathways. In conclusion, Li neuroprotectionwith regard to cannabinoid abstinence may occur through the regulation of the p-ERK1/2 cascade inconsequent of p-GSK-3β signaling pathways in rats.

  5. Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation

    Science.gov (United States)

    Civier, Oren; Bullock, Daniel; Max, Ludo; Guenther, Frank H.

    2013-01-01

    A typical white-matter integrity and elevated dopamine levels have been reported for individuals who stutter. We investigated how such abnormalities may lead to speech dysfluencies due to their effects on a syllable-sequencing circuit that consists of basal ganglia (BG), thalamus, and left ventral premotor cortex (vPMC). “Neurally impaired” versions of the neurocomputational speech production model GODIVA were utilized to test two hypotheses: (1) that white-matter abnormalities disturb the circuit via corticostriatal projections carrying copies of executed motor commands, and (2) that dopaminergic abnormalities disturb the circuit via the striatum. Simulation results support both hypotheses: in both scenarios, the neural abnormalities delay readout of the next syllable’s motor program, leading to dysfluency. The results also account for brain imaging findings during dysfluent speech. It is concluded that each of the two abnormality types can cause stuttering moments, probably by affecting the same BG-thalamus-vPMC circuit. PMID:23872286

  6. A murine experimental anthracycline extravasation model: pathology and study of the involvement of topoisomerase II alpha and iron in the mechanism of tissue damage

    DEFF Research Database (Denmark)

    2010-01-01

    The bisdioxopiperazine topoisomerase II catalytic inhibitor dexrazoxane has successfully been introduced into the clinic as an antidote to accidental anthracycline extravasation based on our preclinical mouse studies. The histology of this mouse extravasation model was investigated and found...... with dense dermal connective tissue. The extension of this fibrosis was quantified, and dexrazoxane intervention resulted in a statistically significant decrease in fibrosis extension, as also observed in the clinic. Several mechanisms have been proposed in anthracycline extravasation cytotoxicity, and we...... tested two major hypotheses: (1) interaction with topoisomerase II alpha and (2) the formation of tissue damaging reactive oxygen species following redox cycling of an anthracycline Fe(2+) complex. Dexrazoxane could minimise skin damage via both mechanisms, as it stops the catalytic activity...

  7. A novel TCR transgenic model reveals that negative selection involves an immediate, Bim-dependent pathway and a delayed, Bim-independent pathway.

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    Damian Kovalovsky

    Full Text Available A complete understanding of negative selection has been elusive due to the rapid apoptosis and clearance of thymocytes in vivo. We report a TCR transgenic model in which expression of the TCR during differentiation occurs only after V(DJ-like recombination. TCR expression from this transgene closely mimics expression of the endogenous TCRalpha locus allowing for development that is similar to wild type thymocytes. This model allowed us to characterize the phenotypic changes that occurred after TCR-mediated signaling in self-reactive thymocytes prior to their deletion in a highly physiological setting. Self-reactive thymocytes were identified as being immature, activated and CD4(loCD8(lo. These cells had upregulated markers of negative selection and were apoptotic. Elimination of Bim reduced the apoptosis of self-reactive thymocytes, but it did not rescue their differentiation and the cells remained at the immature CD4(loCD8(lo stage of development. These cells upregulate Nur77 and do not contribute to the peripheral T cell repertoire in vivo. Remarkably, development past the CD4(loCD8(lo stage was possible once the cells were removed from the negatively selecting thymic environment. In vitro development of these cells occurred despite their maintenance of high intracellular levels of Nur77. Therefore, in vivo, negatively selected Bim-deficient thymocytes are eliminated after prolonged developmental arrest via a Bim-independent pathway that is dependent on the thymic microenvironment. These data newly reveal a layering of immediate, Bim-dependent, and delayed Bim-independent pathways that both contribute to elimination of self-reactive thymocytes in vivo.

  8. Structural modeling and mutational analysis of yeast eukaryotic translation initiation factor 5A reveal new critical residues and reinforce its involvement in protein synthesis

    Science.gov (United States)

    Dias, Camila A. O.; Cano, Veridiana S. P.; Rangel, Suzana M.; Apponi, Luciano H.; Frigieri, Mariana C.; Muniz, João R. C.; Garcia, Wanius; Park, Myung H.; Garratt, Richard C.; Zanelli, Cleslei F.; Valentini, Sandro R.

    2017-01-01

    Eukaryotic translation initiation factor 5A (eIF5A) is a protein that is highly conserved and essential for cell viability. This factor is the only protein known to contain the unique and essential amino acid residue hypusine. This work focused on the structural and functional characterization of Saccharomyces cerevisiae eIF5A. The tertiary structure of yeast eIF5A was modeled based on the structure of its Leishmania mexicana homologue and this model was used to predict the structural localization of new site-directed and randomly generated mutations. Most of the 40 new mutants exhibited phenotypes that resulted from eIF-5A protein-folding defects. Our data provided evidence that the C-terminal α-helix present in yeast eIF5A is an essential structural element, whereas the eIF5A N-terminal 10 amino acid extension not present in archaeal eIF5A homologs, is not. Moreover, the mutants containing substitutions at or in the vicinity of the hypusine modification site displayed nonviable or temperature-sensitive phenotypes and were defective in hypusine modification. Interestingly, two of the temperature-sensitive strains produced stable mutant eIF5A proteins – eIF5AK56A and eIF5AQ22H,L93F – and showed defects in protein synthesis at the restrictive temperature. Our data revealed important structural features of eIF5A that are required for its vital role in cell viability and underscored an essential function of eIF5A in the translation step of gene expression. PMID:18341589

  9. Auditory function in the Tc1 mouse model of down syndrome suggests a limited region of human chromosome 21 involved in otitis media.

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    Stephanie Kuhn

    Full Text Available Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21 in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K(+ currents characteristic of control hair cells. However, the size of the large conductance (BK Ca(2+ activated K(+ current (I(K,f, which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active.

  10. [Pulmonary involvements of sarcoidosis].

    Science.gov (United States)

    Ohmichi, M; Hiraga, Y; Hirasawa, M

    1990-01-01

    We reported about intrathoracic changes and prognosis of 686 patients with sarcoidosis diagnosed in our hospital between 1963 and 1988. We evaluated CT findings in 135 patients with sarcoidosis and found pulmonary involvements in 81. We analyzed CT findings according to the classification by Tuengerthal which classified radiographic findings combining ILO classification of pneumoconiosis and characteristic findings of bronchovascular sheath with sarcoidosis. The CT findings were as follows: small opacities (44 out of 81 cases, 54.3%), large opacities (37 cases, 46.7%). Additional findings were as follows: peribronchial marking (42 cases, 51.9%), contraction (17 cases, 21.0%), pleural involvement (9 cases, 11.1%), bulla (5 cases, 6.2%). The characteristic CT findings of serious sarcoidosis were extasis of bronchus, thickening of the bronchial wall, unclearness of vascular shadow, atelectasis and thickening of pleura. Concerning the prognosis of pulmonary involvement, according to age, patients younger than 30 years old at initial diagnosis were better than those of 30 years and over in terms of disappearance of pulmonary involvements. According to stage, patients of stage I and stage II were better than those of stage III. Among the patients we were able to observe chest X-ray findings during five years according to the character of shadow, ill-defined shadow of small opacities and rounded shadows of large opacities had a higher disappearance rate of pulmonary involvements than irregular shadows of large opacities, atelectasis and contraction.

  11. Musculoskeletal involvement in sarcoidosis*, **

    Science.gov (United States)

    Nessrine, Akasbi; Zahra, Abourazzak Fatima; Taoufik, Harzy

    2014-01-01

    Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis), and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-α, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management. PMID:24831403

  12. Musculoskeletal involvement in sarcoidosis

    Directory of Open Access Journals (Sweden)

    Akasbi Nessrine

    2014-04-01

    Full Text Available Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis, and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-α, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management.

  13. Prognostic significance of the initial cerebro-spinal fluid (CSF) involvement of children with acute lymphoblastic leukaemia (ALL) treated without cranial irradiation: results of European Organization for Research and Treatment of Cancer (EORTC) Children Leukemia Group study 58881.

    Science.gov (United States)

    Sirvent, Nicolas; Suciu, Stefan; Rialland, Xavier; Millot, Frédéric; Benoit, Yves; Plantaz, Dominique; Ferster, Alice; Robert, Alain; Lutz, Patrick; Nelken, Brigitte; Plouvier, Emmanuel; Norton, Lucilia; Bertrand, Yves; Otten, Jacques

    2011-01-01

    To evaluate the prognostic significance of the initial cerebro-spinal fluid (CSF) involvement of children with ALL enrolled from 1989 to 1996 in the EORTC 58881 trial. Patients (2025) were categorised according to initial central nervous system (CNS) status: CNS-1 (CNS negative, n=1866), CNS-2 (<5 leucocytes/mm(3), CSF with blasts, n=50), CNS-3 (CNS positive, n=49), TLP+ (TLP with blasts, n=60). CNS-directed therapy consisted in intravenous (i.v.) methotrexate (5 g/sqm) in 4-10 courses, and intrathecal methotrexate injections (10-20), according to CNS status. Cranial irradiation was omitted in all patients. In the CNS1, TLP+, CNS2 and CNS3 group the 8-year EFS rate (SE%) was 69.7% (1.1%), 68.8% (6.2%), 71.3% (6.5%) and 68.3% (6.2%), respectively. The 8-year incidence of isolated CNS relapse (SE%) was 3.4% (0.4%), 1.7% (1.7%), 6.1% (3.5%) and 9.4% (4.5%), respectively, whereas the 8-year isolated or combined CNS relapse incidence was 7.6% (0.6%), 3.5% (2.4%), 10.2% (4.4%) and 11.7% (5.0%), respectively. Patients with CSF blasts had a higher rate of initial bad risk features. Multivariate analysis indicated that presence of blasts in the CSF had no prognostic value: (i) for EFS and OS; (ii) for isolated and isolated or combined CNS relapse; WBC count<25 × 10(9)/L and Medac E-coli asparaginase treatment were each related to a lower CNS relapse risk. The presence of initial CNS involvement has no prognostic significance in EORTC 58881. Intensification of CNS-directed chemotherapy, without CNS radiation, is an effective treatment of initial meningeal leukaemic involvement. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Computer modelling reveals new conformers of the ATP binding loop of Na+/K+-ATPase involved in the transphosphorylation process of the sodium pump

    Science.gov (United States)

    Tejral, Gracian; Sopko, Bruno; Necas, Alois; Schoner, Wilhelm

    2017-01-01

    Hydrolysis of ATP by Na+/K+-ATPase, a P-Type ATPase, catalyzing active Na+ and K+ transport through cellular membranes leads transiently to a phosphorylation of its catalytical α-subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp369 to allow the transfer of ATP’s terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the γ-phosphate group of ATP to the Asp369 is achieved, analogous molecular modeling of the M4–M5 loop of ATPase was performed using the crystal data of Na+/K+-ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr338 and Ile760 of the α2-subunit of Na+/K+-ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation; the first one close to Phe475 in the N-domain, the other one close to Asp369 in the P-domain. However, binding of Mg2+•ATP to any of these sites in the “open conformation” may not lead to phosphorylation of Asp369. Additional conformations of the cytoplasmic loop were found wobbling between “open conformation”  “semi-open conformation  “closed conformation” in the absence of 2Mg2+•ATP. The cytoplasmic loop’s conformational change to the “semi-open conformation”—characterized by a hydrogen bond between Arg543 and Asp611—triggers by binding of 2Mg2+•ATP to a single ATP site and conversion to the “closed conformation” the phosphorylation of Asp369 in the P-domain, and hence the start of Na+/K+-activated ATP hydrolysis. PMID:28316890

  15. Computer modelling reveals new conformers of the ATP binding loop of Na+/K+-ATPase involved in the transphosphorylation process of the sodium pump

    Directory of Open Access Journals (Sweden)

    Gracian Tejral

    2017-03-01

    Full Text Available Hydrolysis of ATP by Na+/K+-ATPase, a P-Type ATPase, catalyzing active Na+ and K+ transport through cellular membranes leads transiently to a phosphorylation of its catalytical α-subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp369 to allow the transfer of ATP’s terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the γ-phosphate group of ATP to the Asp369 is achieved, analogous molecular modeling of the M4–M5 loop of ATPase was performed using the crystal data of Na+/K+-ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr338 and Ile760 of the α2-subunit of Na+/K+-ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation; the first one close to Phe475 in the N-domain, the other one close to Asp369 in the P-domain. However, binding of Mg2+•ATP to any of these sites in the “open conformation” may not lead to phosphorylation of Asp369. Additional conformations of the cytoplasmic loop were found wobbling between “open conformation”  “semi-open conformation  “closed conformation” in the absence of 2Mg2+•ATP. The cytoplasmic loop’s conformational change to the “semi-open conformation”—characterized by a hydrogen bond between Arg543 and Asp611—triggers by binding of 2Mg2+•ATP to a single ATP site and conversion to the “closed conformation” the phosphorylation of Asp369 in the P-domain, and hence the start of Na+/K+-activated ATP hydrolysis.

  16. Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury

    Directory of Open Access Journals (Sweden)

    Daniela Hoeber

    2016-01-01

    Full Text Available Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg at the onset of hyperoxia (24 hours, 80% oxygen in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

  17. Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2016-01-01

    Full Text Available The degenerative loss through apoptosis of dopaminergic neurons in the substantia nigra pars compacta plays a primary role in the progression of Parkinson’s disease (PD. Our in vitro experiments suggested that salidroside (Sal could protect against 1-methyl-4-phenylpyridine-induced cell apoptosis in part by regulating the PI3K/Akt/GSK3β pathway. The current study aims to increase our understanding of the protective mechanisms of Sal in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine- (MPTP- induced PD mouse model. We found that pretreatment with Sal could protect against MPTP-induced increase of the time of turning downwards and climbing down to the floor. Sal also prevented MPTP-induced decrease of locomotion frequency and the increase of the immobile time. Sal provided a protection of in MPTP-induced loss of tyrosine hydroxylase-positive neurons in SNpc and the level of DA, DOPAC, and HVA in the striatum. Furthermore, Sal could increase the phosphorylation level of Akt and GSK3β, upregulate the ratio of Bcl-2/Bax, and inhibit the activation of caspase-3, caspase-6, and caspase-9. These results show that Sal prevents the loss of dopaminergic neurons and the PI3K/Akt/GSK3β pathway signaling pathway may have mediated the protection of Sal against MPTP, suggesting that Sal may be a potential candidate in neuroprotective treatment for PD.

  18. Mouse model of testosterone-induced muscle fiber hypertrophy: involvement of p38 mitogen-activated protein kinase-mediated Notch signaling.

    Science.gov (United States)

    Brown, Danielle; Hikim, Amiya P Sinha; Kovacheva, Ekaterina L; Sinha-Hikim, Indrani

    2009-04-01

    As a prerequisite for studies using mutant mice, we established a mouse model for investigating the molecular mechanisms by which testosterone (T) promotes muscle growth. Groups of six adult male mice (C57BL/6) received one of the following treatments: 1) vehicle (sterile distilled water; normal control) and 2) GnRH antagonist with empty (sham control) or 2 cm T- filled implant. Mice were killed 2, 6, and 8 weeks after treatment. T treatment for 8 weeks resulted in a significant (Pmuscles. T-induced fiber-hypertrophy was accompanied by up-regulation of the Notch ligand Delta 1 and activation of Notch signaling, as evidenced by increase in activated forms of Notch 1 and Notch 2. Consistent with this, we also observed an increase in the number of proliferating cell nuclear antigen (PCNA)-positive nuclei in muscles of T-treated mice, indicating that activation of Notch signaling enhanced cell proliferation. T supplementation not only triggered p38 mitogen-activated protein kinase (MAPK) activation but also concurrently inhibited c-Jun NH(2)-terminal kinase (JNK) activation within 2 weeks of treatment. Concomitant administration of SB203580, a p38 MAPK inhibitor, effectively blocked T-induced activation of Notch signaling and significantly (Pmuscle fiber hypertrophy through activation of Notch signaling and the inactivation of JNK together with the activation of p38 MAPK may be critical for T-induced activation of Notch signaling and, as a consequence, muscle fiber hypertrophy.

  19. The role of genes involved in stress, neural plasticity, and brain circuitry in depressive phenotypes: Convergent findings in a mouse model of neglect

    Science.gov (United States)

    Montalvo-Ortiz, Janitza L; Bordner, Kelly A.; Carlyle, Becky C.; Gelernter, Joel; Simen, Arthur A.; Kaufman, Joan

    2017-01-01

    Early life neglect increases risk for the development of psychopathologies during childhood and adulthood, including depression and anxiety disorders. We recently reported epigenetic changes in DNA derived from saliva in three genes predicted depression in a cohort of maltreated children: DNA-binding protein inhibitor ID-3 (ID3), Glutamate NMDA Receptor (GRIN1), and Tubulin Polymerization Promoting Protein (TPPP). To validate the role of these genes in depression risk, secondary analyses were conducted of gene expression data obtained from medial prefrontal cortex (mPFC) tissue of mice subjected to a model of maternal neglect which included maternal separation and early weaning (MSEW). Anxiety and depression-like phenotype data derived using the elevated plus maze (EPM) and forced swimming test (FST), respectively, were also available for secondary analyses. Behavioral tests were conducted in MSEW and control adult male mice when they were between 65 and 80 days old. ID3, GRIN1 and TPPP gene expression in the mPFC were found to significantly predict behavioral differences in the EPM and FST. These results further support the role of these genes in the etiology of depressive and anxiety phenotypes following early life stress. PMID:27506655

  20. A theoretical model investigation of peptide bond formation involving two water molecules in ribosome supports the two-step and eight membered ring mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qiang [School of Chemistry & Chemical Engineering, Shandong University, Jinan 250100 (China); Gao, Jun, E-mail: gaojun@sdu.edu.cn [Agricultural Bioinformatics Key Laboratory of Hubei Province, College of Informatics, Huazhong Agricultural University, Wuhan 430070 (China); School of Chemistry & Chemical Engineering, Shandong University, Jinan 250100 (China); Zhang, Dongju; Liu, Chengbu [School of Chemistry & Chemical Engineering, Shandong University, Jinan 250100 (China)

    2015-04-01

    Highlights: • We theoretical studied peptide bond formation reaction mechanism with two water molecules. • The first water molecule can decrease the reaction barriers by forming hydrogen bonds. • The water molecule mediated three-proton transfer mechanism is the favorable mechanism. • Our calculation supports the two-step and eight membered ring mechanism. - Abstract: The ribosome is the macromolecular machine that catalyzes protein synthesis. The kinetic isotope effect analysis reported by Strobel group supports the two-step mechanism. However, the destination of the proton originating from the nucleophilic amine is uncertain. A computational simulation of different mechanisms including water molecules is carried out using the same reaction model and theoretical level. Formation the tetrahedral intermediate with proton transfer from nucleophilic nitrogen, is the rate-limiting step when two water molecules participate in peptide bond formation. The first water molecule forming hydrogen bonds with O9′ and H15′ in the A site can decrease the reaction barriers. Combined with results of the solvent isotope effects analysis, we conclude that the three-proton transfer mechanism in which water molecule mediate the proton shuttle between amino and carbon oxygen in rate-limiting step is the favorable mechanism. Our results will shield light on a better understand the reaction mechanism of ribosome.

  1. Transient Receptor Potential Channel and Interleukin-17A Involvement in LTTL Gel Inhibition of Bone Cancer Pain in a Rat Model.

    Science.gov (United States)

    Wang, Juyong; Zhang, Ruixin; Dong, Changsheng; Jiao, Lijing; Xu, Ling; Liu, Jiyong; Wang, Zhengtao; Lao, Lixing

    2015-07-01

    Cancer pain management is a challenge for which Chinese herbal medicine might be useful. To study the spinal mechanisms of the Chinese medicated gel Long-Teng-Tong-Luo (LTTL), a 7-herb compound, on bone cancer pain, a bone cancer pain model was made by inoculating the tibias of female rats with Walker 256 cells. LTTL gel or inert gel, 0.5 g/cm(2)/d, was applied to the skin of tumor-bearing tibias for 21 days beginning a day after the inoculation. Mechanical threshold and paw withdrawal latency to thermal stimulation was measured. Transient receptor potential (TRP) cation channels in lumbar dorsal root ganglia (DRG) were immunostained and counted, and lumbar spinal cord interleukin-17A (IL-17A) was measured with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. TRP antagonists and interleukin (IL)-17A antibodies were intrathecally administered to determine their effects on bone cancer pain. The gel significantly (P gel inhibits cancer pain, and this might be accounted for by the decrease in expression of DRG TRP channels and spinal astrocyte IL-17A.

  2. Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury.

    Science.gov (United States)

    Hoeber, Daniela; Sifringer, Marco; van de Looij, Yohan; Herz, Josephine; Sizonenko, Stéphane V; Kempe, Karina; Serdar, Meray; Palasz, Joanna; Hadamitzky, Martin; Endesfelder, Stefanie; Fandrey, Joachim; Felderhoff-Müser, Ursula; Bendix, Ivo

    2016-01-01

    Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80% oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity.

  3. Involve physicians in marketing.

    Science.gov (United States)

    Randolph, G T; Baker, K M; Laubach, C A

    1984-01-01

    Many everyday problems in medical group practice can be attacked by a marketing approach. To be successful, however, this kind of approach must have the full support of those involved, especially the physicians, since they are the principal providers of healthcare services. When marketing is presented in a broad context, including elements such as patient mix, population distribution, and research, physicians are more likely to be interested and supportive. The members of Geisinger Medical Center's Department of Cardiovascular Medicine addressed their patient appointment backlog problem with a marketing approach. Their method is chronicled here and serves as a fine example of how physician involvement in marketing can lead to a positive outcome.

  4. Anti-Inflammatory and Antinociceptive Effects of Salbutamol on Acute and Chronic Models of Inflammation in Rats: Involvement of an Antioxidant Mechanism

    Directory of Open Access Journals (Sweden)

    Hulya Uzkeser

    2012-01-01

    Full Text Available The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO activity and lipid peroxidation (LPO level and increased the activity of superoxide dismutase (SOD and level of glutathione (GSH during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

  5. Synergistic Interaction of Light Alcohol Administration in the Presence of Mild Iron Overload in a Mouse Model of Liver Injury: Involvement of Triosephosphate Isomerase Nitration and Inactivation

    Science.gov (United States)

    Gao, Wanxia; Zhao, Jie; Gao, Zhonghong

    2017-01-01

    It is well known that iron overload promotes alcoholic liver injury, but the doses of iron or alcohol used in studies are usually able to induce liver injury independently. Little attention has been paid to the coexistence of low alcohol consumption and mild iron overload when either of them is insufficient to cause obvious liver damage, although this situation is very common among some people. We studied the interactive effects and the underlining mechanism of mild doses of iron and alcohol on liver injury in a mouse model. Forty eight male Kunming mice were randomly divided into four groups: control, iron (300 mg/kg iron dextran, i.p.), alcohol (2 g/kg/day ethanol for four weeks i.g.), and iron plus alcohol group. After 4 weeks of treatment, mice were sacrificed and blood and livers were collected for biochemical analysis. Protein nitration level in liver tissue was determined by immunoprecipitation and Western blot analysis. Although neither iron overload nor alcohol consumption at our tested doses can cause severe liver injury, it was found that co-administration of the same doses of alcohol and iron resulted in liver injury and hepatic dysfunction, accompanied with elevated ratio of NADH/NAD+, reduced antioxidant ability, increased oxidative stress, and subsequent elevated protein nitration level. Further study revealed that triosephosphate isomerase, an important glycolytic enzyme, was one of the targets to be oxidized and nitrated, which was responsible for its inactivation. These data indicate that even under low alcohol intake, a certain amount of iron overload can cause significant liver oxidative damage, and the modification of triosephosphate isomerasemight be the important underlining mechanism of hepatic dysfunction. PMID:28103293

  6. The Involvement of Corin in the Progression of Diabetic Erectile Dysfunction in a Rat Model by Down-Regulating ANP /NO/cGMP Signal Pathway.

    Science.gov (United States)

    Wang, Jian; Mi, Yuanyuan; Yuan, Fenglai; Wu, Sheng; You, Xiaoming; Dai, Feng; Huang, Yi; Cao, Jia; Zhu, Jin; Xue, Boxin; Zhu, Lijie

    2017-01-20

    This study was aimed to analyze the potential role of Corin in the procession of diabetic ED and to explore the underlying mechanism. Diabetic ED rat model was constructed and the characteristics of diabetic ED and control rats were recorded at 4, 8, 12 and 16 weeks. qRT-PCR and Western bloting were used to detected the mRNA and protein levels. Intracellular cGMP detection was accomplished using a commercial radioimmunoassay method. Vascular endothelial cell from rat corpus cavernosum spiral artery was isolated and transfected with si- Corin to analyzed the potential role of Corin. Cell viability was assessed using crystal violet. The results showed that diabetic ED rats showed significantly higher glucose level, and lower body weight, ICP level and ICP/MAP ratio at 12 and 16 weeks in diabetic ED rats compared with control rats. The protein levels of Corin, atrial natriuretic peptide (ANP)and eNOS, and the level of cGMP were significantly down-regulated in corpus cavernosum in diabetic ED rats, revealing the potential role of Corin in NO-associated diabetic ED. Further studies proved that defect of Corin not only inhibited the vascular endothelial cell viability in high-glucose condition, but also suppressed ANP, eNOS and cGMP expression in vascular endothelial cells. To sum up, Corin contributes to the progression of diabetic ED and the underlying mechanism is associated with the down-regulation of ANP /NO/cGMP signal pathway. This article is protected by copyright. All rights reserved.

  7. Anti-inflammatory and antinociceptive effects of salbutamol on acute and chronic models of inflammation in rats: involvement of an antioxidant mechanism.

    Science.gov (United States)

    Uzkeser, Hulya; Cadirci, Elif; Halici, Zekai; Odabasoglu, Fehmi; Polat, Beyzagul; Yuksel, Tugba Nurcan; Ozaltin, Seda; Atalay, Fadime

    2012-01-01

    The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg) effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO) activity and lipid peroxidation (LPO) level and increased the activity of superoxide dismutase (SOD) and level of glutathione (GSH) during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

  8. Involvement of TRPV1 channels in the activity of the cannabinoid WIN 55,212-2 in an acute rat model of temporal lobe epilepsy.

    Science.gov (United States)

    Carletti, Fabio; Gambino, Giuditta; Rizzo, Valerio; Ferraro, Giuseppe; Sardo, Pierangelo

    2016-05-01

    The exogenous cannabinoid agonist WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), has revealed to play a role on modulating the hyperexcitability phenomena in the hippocampus. Cannabinoid-mediated mechanisms of neuroprotection have recently been found to imply the modulation of transient receptor potential vanilloid 1 (TRPV1), a cationic channel subfamily that regulate synaptic excitation. In our study, we assessed the influence of pharmacological manipulation of TRPV1 function, alone and on WIN antiepileptic activity, in the Maximal Dentate Activation (MDA) acute model of temporal lobe epilepsy. Our results showed that the TRPV1 agonist, capsaicin, increased epileptic outcomes; whilst antagonizing TRPV1 with capsazepine exerts a protective role on paroxysmal discharge. When capsaicin is co-administered with WIN effective dose of 10mg/kg is able to reduce its antiepileptic strength, especially on the triggering of MDA response. Accordingly, capsazepine at the protective dose of 2mg/kg managed to potentiate WIN antiepileptic effects, when co-treated. Moreover, WIN subeffective dose of 5mg/kg was turned into effective when capsazepine comes into play. This evidence suggests that systemic administration of TRPV1-active drugs influences electrically induced epilepsy, with a noticeable protective activity for capsazepine. Furthermore, results from the pharmacological interaction with WIN support an interplay between cannabinoid and TRPV1 signaling that could represent a promising approach for a future pharmacological strategy to challenge hyperexcitability-based diseases.

  9. Don’t let up: implementing and sustaining change in a new post-licensure education model for developing extended role practitioners involved in arthritis care

    Directory of Open Access Journals (Sweden)

    Lundon K

    2015-08-01

    Full Text Available Katie Lundon,1,3 Rachel Shupak,1–3 Sonya Canzian,4 Ed Ziesmann,5 Rayfel Schneider,6,71Office of Continuing Professional Development, Faculty of Medicine, University of Toronto, 2Division of Rheumatology, St Michael's Hospital, 3Department of Medicine, University of Toronto, 4Trauma/Neurosurgery and Mobility Programs, St Michael's Hospital, 5Programs and Services, The Arthritis Society, 6Division of Rheumatology, The Hospital for Sick Children, 7Department of Paediatrics, University of Toronto, Toronto, ON, CanadaKey message: Across a 9-year period, the Advanced Clinician Practitioner in Arthritis Care program has achieved a set of short-term “wins” giving direction and momentum to the development of new roles for health care practitioners providing arthritis care.Implications: This is a viable model for post-licensure training offered to multiple allied health professionals to support the development of competent extended role practitioners (extended scope practice. Challenges at this critical juncture include: retain focus, drive, and commitment; develop academic and financial partnerships transferring short-term success to long-term sustainability; advanced, context-driven, system-level evaluation including fiscal outcome; health care policy adaptation to new human health resource development.Supporting evidence: Success includes: completed 2-year health services research evaluating 37 graduates; leadership, innovation, educational excellence, and human health resource benefit awards; influential publications/presentations addressing post-licensure education/outcome, interprofessional collaboration, and improved patient care. Keywords: human health resource development, post-licensure education, arthritis, extended role practitioners, allied health professionals

  10. Reaching Parents Through Involvement

    Science.gov (United States)

    Schmerber, Ronald J.

    1974-01-01

    The parent involvement program evolved from the needs of parents. Basic to the program is the concept of parenting, which implies taking positive action to facilitate and meet the needs of the children ahe family. Parents participate in the development, implementation, and evaluation of their child's program. (Author)

  11. Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model.

    Science.gov (United States)

    Qiu, Shujuan; Sun, Guiling; Zhang, Yunxia; Li, Xiangling; Wang, Rong

    2016-05-01

    The aim of the present study was to investigate the renoprotective effects of isorhamnetin (ISO) in type 2 diabetic rats and its effects on the nuclear factor-κB (NF-κB) signaling pathway, which is associated with diabetic nephropathy. The type 2 diabetic rat model was established by a high-fat diet plus streptozocin injection and the rats were subsequently treated with two dosages of ISO, respectively. The levels of blood glucose were determined. Urinary osteopontin, kidney injury molecule-1 (KIM-1) and albumin were measured to evaluate the renal function of the rats. Renal NF-κB signaling activity was assessed by measuring the levels of NF-κB p65, phospho-NF-κB p65, inhibitor of NF-κB (IκBα) and phospho-IκBα, and the NF-κB p65 DNA-binding activity. Downstream inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-β1 (TGF-β1)] of the NF-κB signaling pathway were investigated to evaluate the renal inflammatory response. Renal levels of malondialdehyde and total superoxide dismutase were detected to access the oxidative stress. Furthermore, glomerular mesangial cells (GMCs) were treated with lipopolysaccharide and ISO. In the cellular experiment, the NF-κB signaling activity, levels of TNF-α, IL-1β, IL-6, ICAM-1 and TGF-β1, and oxidative stress were also investigated. The results showed that ISO decreased the levels of urinary osteopontin, KIM-1 and albumin. ISO also inhibited the NF-κB signaling activity, decreased the production of inflammatory mediators and attenuated oxidative stress in diabetic rats and GMCs. The present investigations revealed that ISO had ameliorative effects on diabetes-induced renal damage and the activity may be associated with the negative regulation of NF-κB signaling pathway.

  12. Microorganisms involved in MIC

    Energy Technology Data Exchange (ETDEWEB)

    Sorensen, K. [Danish Technological Institute (Denmark)

    2011-07-01

    Microbiologically influenced corrosion (MIC) is a widespread problem that is difficult to detect and assess because of its complex mechanism. This paper presents the involvement of microorganisms in MIC. Some of the mechanisms that cause MIC include hydrogen consumption, production of acids, anode-cathode formation and electron shuttling. A classic bio-corrosive microorganism in the oil and gas industry is sulphate-reducing prokaryotes (SRP). Methanogens also increase corrosion rates in metals. Some of the phylogenetic orders detected while studying SRP and methanogens are archaeoglobales, clostridiales, methanosarcinales and methanothermococcus. There were some implications, such as growth of SRP not being correlated with growth of methanogens; methanogens were included in MIC risk assessment. A few examples are used to display how microorganisms are involved in topside corrosion and microbial community in producing wells. From the study, it can be concluded that, MIC risk assessment includes system data and empirical knowledge of the distribution and number of microorganisms in the system.

  13. Involved Node Radiation Therapy

    DEFF Research Database (Denmark)

    Maraldo, Maja V; Aznar, Marianne C; Vogelius, Ivan R

    2012-01-01

    PURPOSE: The involved node radiation therapy (INRT) strategy was introduced for patients with Hodgkin lymphoma (HL) to reduce the risk of late effects. With INRT, only the originally involved lymph nodes are irradiated. We present treatment outcome in a retrospective analysis using this strategy...... to 36 Gy). Patients attended regular follow-up visits until 5 years after therapy. RESULTS: The 4-year freedom from disease progression was 96.4% (95% confidence interval: 92.4%-100.4%), median follow-up of 50 months (range: 4-71 months). Three relapses occurred: 2 within the previous radiation field......, and 1 in a previously uninvolved region. The 4-year overall survival was 94% (95% confidence interval: 88.8%-99.1%), median follow-up of 58 months (range: 4-91 months). Early radiation therapy toxicity was limited to grade 1 (23.4%) and grade 2 (13.8%). During follow-up, 8 patients died, none from HL, 7...

  14. Between Involvement and Detachment

    DEFF Research Database (Denmark)

    Thomasen, Gry

    Between Involvement and Detachment takes grasp with the Johnson administration’s (1963-1969) perceptions of and responses to the Western European realignments. Arguing that the Johnson administration set out to maintain the American unilateralist position in the transatlantic relation, not just a...... the administration maintained. Despite changed circumstances, the Nixon administration’s relation with and perceptions of the European allies largely resemble the traditionalist view of the Johnson administration....

  15. Joint involvement in Ochronosis

    OpenAIRE

    Biehl, Christoph; Thormann, U.; Madera, N.; Heiß, C

    2016-01-01

    Introduction: Ochronosis is a metabolic disorder that is usually associated with the typical brown-black colored urine and retention of phenol complexes in sclera and skin. Kidney and heart are also checked, the disease can also cause damage in these organs. The disease is less associated with degenerative changes in the joints of the limbs and the spine. Methods: We report on the progress of a patient with documented family history on alcaptonuria and joint involvement. In the age of 69 ...

  16. Involvement Without Participation?

    DEFF Research Database (Denmark)

    Olsén, Peter

    2012-01-01

    The article presents a case study of a knowledge-intensive company that launched a 2-year project to improve their psychosocial working environment. All parties agreed on the project, and the methods used aimed to promote the involvement of the employees. Surprisingly, the psychosocial working...... and participation. In order to develop a more sustainable and viable psychosocial working environment, a broader and more democratic notion of organisational learning and managing is proposed....

  17. Getting involved in research.

    Science.gov (United States)

    Banner, Davina; Grant, Lyle G

    2011-01-01

    The need for quality nursing research to promote evidence-based practice and optimize patient care is well recognized. This is particularly pertinent in cardiovascular nursing, where cardiovascular disease continues to be the leading cause of morbidity and mortality worldwide (World Health Organization, 2007). Across the spectrum of academic, clinical, and health care administration nursing roles, research remains fundamental to bridging theory, practice, and education (LoBiondo-Wood, Haber, Cameron, & Singh, 2009). Despite recognition of the importance of nursing research, the gap between research and practice continues to be an ongoing issue (Funk, Tornquist, & Champagne, 1995; Pettengill, Gillies, & Clark, 1994; Rizzuto, Bostrom, Suterm, & Chenitz, 1994; Rolfe, 1998). Nurses are appropriately situated to contribute to research that improves clinical outcomes and health service delivery. However, the majority of nurses in clinical practice do not have a significant research component structured into their nursing role. In this research column, the authors outline the importance of nurses being engaged in research and present some different levels of involvement that nurses may assume. A continuum of nursing research involvement includes asking researchable questions, being a savvy consumer of research evidence, finding your own level of research involvement, and aspiring to lead.

  18. Influences of Product Involvement, Environmental Message and ...

    African Journals Online (AJOL)

    Influences of Product Involvement, Environmental Message and Green ... The study employs an empirical research by 2x2x2 between subject factorial design. ... Advertising Appeals, Green Marketing, Elaboration Likelihood Model (ELM) ...

  19. Cellular senescence and autophagy of myoepithelial cells are involved in the progression of in situ areas of carcinoma ex-pleomorphic adenoma to invasive carcinoma. An in vitro model.

    Science.gov (United States)

    Silva, Carolina Amália Barcellos; Martinez, Elizabeth Ferreira; Demasi, Ana Paula Dias; Altemani, Albina; da Silveira Bossonaro, Jeruza Pinheiro; Araújo, Ney Soares; de Araújo, Vera Cavalcanti

    2015-09-01

    During tumor invasion, benign myoepithelial cells of carcinoma ex-pleomorphic adenoma (CXPA) surround malignant epithelial cells and disappear. The mechanisms involved in the death and disappearance of these myoepithelial cells were investigated via analysis of the expression of regulatory proteins for apoptosis, autophagy and cellular senescence in an in situ in vitro model. Protein expression relating to apoptosis (Bax, Bcl-2, Survivin), autophagy (Beclin-1, LC3B) and cellular senescence (p21, p16) was evaluated using indirect immunofluorescence. β-galactosidase expression was assessed via histochemistry. Biopsies of CXPA (ex vivo) allowed immunhistochemical evaluation of p21 and p16, whilst LC3B, p21 and p16 protein expression was analyzed by western blotting. In the in vitro model, the myoepithelial cells were positive for LC3B (cytoplasm) and p21 (nucleus), whilst in vivo positivity for p21 and p16 was observed. In vitro, β-galactosidase activity increased in the myoepithelial cells over time. Western blotting analysis revealed an increased LC3B, p16 and p21 expression in the myoepithelial cells with previous contact with the malignant cells when compared with those without contact. The investigation of behavior of benign myoepithelial cells in ductal areas of CXAP revealed that the myoepithelial cells are involved in the autophagy-senescence phenotype that subsequently leads to their disappearance.

  20. Oral treatment with Saccharomyces cerevisiae strain UFMG 905 modulates immune responses and interferes with signal pathways involved in the activation of inflammation in a murine model of typhoid fever.

    Science.gov (United States)

    Martins, Flaviano S; Elian, Samir D A; Vieira, Angélica T; Tiago, Fabiana C P; Martins, Ariane K S; Silva, Flávia C P; Souza, Ericka L S; Sousa, Lirlândia P; Araújo, Helena R C; Pimenta, Paulo F; Bonjardim, Cláudio A; Arantes, Rosa M E; Teixeira, Mauro M; Nicoli, Jacques R

    2011-04-01

    Salmonella spp. are Gram-negative, facultative, intracellular pathogens that cause several diarrheal diseases ranging from self-limiting gastroenteritis to typhoid fever. Previous results from our laboratory showed that Saccharomyces cerevisiae strain UFMG 905 isolated from 'cachaça' production presented probiotic properties due to its ability to protect against experimental infection with Salmonella enterica serovar Typhimurium. In this study, the effects of oral treatment with S. cerevisiae 905 were evaluated at the immunological level in a murine model of typhoid fever. Treatment with S. cerevisiae 905 inhibited weight loss and increased survival rate after Salmonella challenge. Immunological data demonstrated that S. cerevisiae 905 decreased levels of proinflammatory cytokines and modulated the activation of mitogen-activated protein kinases (p38 and JNK, but not ERK1/2), NF-κB and AP-1, signaling pathways which are involved in the transcriptional activation of proinflammatory mediators. Experiments in germ-free mice revealed that probiotic effects were due, at least in part, to the binding of Salmonella to the yeast. In conclusion, S. cerevisiae 905 acts as a potential new biotherapy against S. Typhimurium infection due to its ability to bind bacteria and modulate signaling pathways involved in the activation of inflammation in a murine model of typhoid fever.

  1. TOGA: A TOUGH code for modeling three-phase, multi-component, and non-isothermal processes involved in CO2-based Enhanced Oil Recovery

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Lehua [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Oldenburg, Curtis M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)

    2016-10-10

    TOGA is a numerical reservoir simulator for modeling non-isothermal flow and transport of water, CO2, multicomponent oil, and related gas components for applications including CO2-enhanced oil recovery (CO2-EOR) and geologic carbon sequestration in depleted oil and gas reservoirs. TOGA uses an approach based on the Peng-Robinson equation of state (PR-EOS) to calculate the thermophysical properties of the gas and oil phases including the gas/oil components dissolved in the aqueous phase, and uses a mixing model to estimate the thermophysical properties of the aqueous phase. The phase behavior (e.g., occurrence and disappearance of the three phases, gas + oil + aqueous) and the partitioning of non-aqueous components (e.g., CO2, CH4, and n-oil components) between coexisting phases are modeled using K-values derived from assumptions of equal-fugacity that have been demonstrated to be very accurate as shown by comparison to measured data. Models for saturated (water) vapor pressure and water solubility (in the oil phase) are used to calculate the partitioning of the water (H2O) component between the gas and oil phases. All components (e.g., CO2, H2O, and n hydrocarbon components) are allowed to be present in all phases (aqueous, gaseous, and oil). TOGA uses a multiphase version of Darcy’s Law to model flow and transport through porous media of mixtures with up to three phases over a range of pressures and temperatures appropriate to hydrocarbon recovery and geologic carbon sequestration systems. Transport of the gaseous and dissolved components is by advection and Fickian molecular diffusion. New methods for phase partitioning and thermophysical property modeling in TOGA have been validated against experimental data published in the literature for describing phase partitioning and phase behavior. Flow and transport has been verified by testing against related TOUGH2 EOS modules and

  2. Involvement in Physical Activity

    Directory of Open Access Journals (Sweden)

    James Gavin

    2013-04-01

    Full Text Available A total of 1,096 adolescents participated in 123 focus groups regarding the perceived outcomes of their involvement in sports and physical activity (PA. The groups, segmented by grade level, sex, and school types, were conducted in both public and private high schools in Montreal, Quebec. We sought to understand, through the participants’ own words, their perception of the outcome matrix of involvement in sports and PA. Focus group questions emphasized changes that adolescents associated with such engagement. In particular, participants were asked how sports and PA might influence behaviors, emotional states, personal characteristics, and other outcomes. Twelve themes were identified in the responses: Positive Health and Physical Changes (18.5%, Activity-Related Positive Emotions (15.6%, and Personal Learning (11.3% were most prevalent in the discussions. A cluster of deeper personal changes thematically described as Self-Identity, Autonomy, and Positive Character Development accounted for another 16.5% of the responses. Relatively few commentaries emphasized negative effects (7.1%. Converting the proportions of qualitative data into a quantitative index allowed us to analyze potential differences in emphasis according to sex, age, and school type. Though a few significant findings emerged, the larger pattern was of a uniform perceptual map across the variables for this adolescent sample. Implications drawn from this investigation highlight the need to clearly articulate concrete pathways to positive nonphysical changes (e.g., mood states, autonomy, positive character development from engagements in sports and PA.

  3. The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors.

    Science.gov (United States)

    Tomić, Maja A; Pecikoza, Uroš B; Micov, Ana M; Stepanović-Petrović, Radica M

    2015-12-01

    Many clinical pain states that are difficult to treat share a common feature of sensitization of nociceptive pathways. Drugs that could normalize hyperexcitable neural activity (e.g., antiepileptic drugs) may be useful in relieving these pain states. Eslicarbazepine acetate (ESL) is a novel antiepileptic drug derived from carbamazepine/oxcarbazepine with a more favorable metabolic profile and potentially better tolerability. We examined the efficacy of ESL in models of inflammatory and neuropathic pain and the potential mechanism involved in its action. The antinociceptive effects of ESL were assessed in mice models of trigeminal (orofacial formalin test), neuropathic (streptozotocin-induced diabetic neuropathy model), and visceral pain (writhing test). The influence of 5-HT1B/1D serotonin receptor (GR 127935) and CB1 (AM251) and CB2 cannabinoid receptor (AM630) antagonists on the antinociceptive effect of ESL was tested in the model of trigeminal pain. ESL exhibited significant and dose-dependent antinociceptive effects in the second phase of the orofacial formalin test (P ≤ 0.011), in the tail-flick test in diabetic mice (P ≤ 0.013), and in the writhing test (P ≤ 0.003). GR 127935 (P ≤ 0.038) and AM251 and AM630 (P ≤ 0.013 for both antagonists) significantly inhibited the antinociceptive effect of ESL in a dose-related manner. ESL exhibited efficacy in models of trigeminal, neuropathic, and visceral pain. In the trigeminal pain model, the antinociceptive effect of ESL is, at least in part, mediated by 5-HT1B/1D serotonin and CB1/CB2 cannabinoid receptors. This study indicates that ESL could be useful in the clinical treatment of inflammatory and neuropathic pain.

  4. Intervention or Involvement

    DEFF Research Database (Denmark)

    Liebst, Lasse Suonperä; Ejbye-Ernst, Peter; Heinskou, Marie Bruvik

    patrons plays in bouncers’ use of violence. To address this gap, we offer a micro-interactional analysis of violent behavior of bouncers. We observed video surveillance footage of naturally occurring barroom conflicts involving bouncers. A quantitative analysis shows that violence is relatively uncommon......, and when it occurs, it is associated with interactions where bouncers are a party to the conflict, compared to situations where they intervene as a third party. Further, a visual analysis of emotional cues identifies anger as a plausible mechanism leading bouncers to practice violent aggression. Thus......, adding to the situational and cultural interpretations in the literature, this study highlights interactional structures as a feature influencing the likelihood of violent bouncer behavior. In considering the implications of our study, we discuss strengths and weaknesses of applying video data analysis...

  5. Between Involvement and Detachment

    DEFF Research Database (Denmark)

    Thomasen, Gry

    a traditional reading of de Gaulle’s policies, and feared that if Gaullist thinking spread among the European allies, it would merit to a return to traditional European power politics. The analysis shows that, by 1964 the administration believed, according to this study, that NATO’s principle of integration......Between Involvement and Detachment takes grasp with the Johnson administration’s (1963-1969) perceptions of and responses to the Western European realignments. Arguing that the Johnson administration set out to maintain the American unilateralist position in the transatlantic relation, not just......, essentially, were detached as America rejected the European reason of state. The Western European realignments were recorded in the Johnson administration with de Gaulle’s critique of US hegemony in Western Europe in the early 1960s. The thesis argues that the administration to a large extent had...

  6. Effectiveness of citizen involvement

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, L. [Prince William Sound Regional Citizen' s Advisory Council, Anchorage, AK (United States)

    2006-07-01

    This paper reviewed the rise of citizen involvement in industry that affects their community. Following the Exxon Valdez oil spill (EVOS) in 1989, the Oil Pollution Act of 1990 provided funding by industry for a citizens group to provide oversite of the Alyeska Pipeline Service Agency terminal and associated tankers. That role is currently filled by the Prince William Sound Regional Citizen's Advisory Council, a volunteer organization that represents communities that were affected by the EVOS. The history of the Prince William Sound Regional Citizen's Advisory Council was discussed along with its structure, funding and overview of projects and research into safer transportation of oil, better oil spill response capabilities and improved environmental protection practices. Some of the successes involving citizen input include the requirement that all tankers going into Prince William Sound be double hull by 2015; a world-class system of tugs escorting tankers in Prince William Sound; installation of an ice-detection radar on a small island near the site of the EVOS; a guidebook for communities affected by man-made disasters; identification of nearshore locations that should be the first to be protected in the case of another spill; and, the installation of a system to capture crude oil vapors when tankers take on cargo. Other projects underway include the study of invasive species that can be transported in the ballast water of tankers, efficacy of dispersants, soil contamination at the tanker loading site, emissions of hazardous air pollutants from ballast water treatment processes, and continual review of emergency response plans. In the 17 years since the formation of the Prince William Sound Regional Citizen's Advisory Council, it has been shown that communication and transparency are the keys to solving complacency, which is believed to have been a contributing factor to the EVOS. 3 refs.

  7. 构建院系教学督导运行模式的探索与实践%Exploration and practice of operating model involved in teaching supervision

    Institute of Scientific and Technical Information of China (English)

    周歧新; 颜家珍; 陈颖; 李勤耕; 赵华; 蒋君好

    2008-01-01

    Teaching supervision is an important part of management system reformation and teaching quality control in the colleges and universities. Among the supervision work the teaching supervision of fac-ulty was worth exploring because of its weak position. The operating model of supervision was involved in the working model and system during the process of teaching supervision. In this article the operating model of "five combinations" about the faculty supervision was advocated according to the practice of teaching su-pervision we took part in at the pharmacy faculty, which will be important for regularization of supervision work at the level of faculty.%教学督导是深化高校管理体制改革、构建高校教学质量监控体系的重要一环.院系一级督导是当前督导工作中的薄弱环节,值得研究和探讨.督导工作运行模式是指教学督导过程中的运作方式系统.本文结合药学院教学督导实践,提出五个结合的院系督导工作运行模式,对于规范院系督导工作、提高督导质量具有重要意义.

  8. Early molecular and behavioral response to lipopolysaccharide in the WAG/Rij rat model of absence epilepsy and depressive-like behavior, involves interplay between AMPK, AKT/mTOR pathways and neuroinflammatory cytokine release.

    Science.gov (United States)

    Russo, Emilio; Andreozzi, Francesco; Iuliano, Rodolfo; Dattilo, Vincenzo; Procopio, Teresa; Fiume, Giuseppe; Mimmi, Selena; Perrotti, Nicola; Citraro, Rita; Sesti, Giorgio; Constanti, Andrew; De Sarro, Giovambattista

    2014-11-01

    The mammalian target of rapamycin (mTOR) pathway has been recently indicated as a suitable drug target for the prevention of epileptogenesis. The mTOR pathway is known for its involvement in the control of the immune system. Since neuroinflammation is recognized as a major contributor to epileptogenesis, we wished to examine whether the neuroprotective effects of mTOR modulation could involve a suppression of the neuroinflammatory process in epileptic brain. We have investigated the early molecular mechanisms involved in the effects of intracerebral administration of the lipopolysaccharide (LPS) in the WAG/Rij rat model of absence epilepsy, in relation to seizure generation and depressive-like behavior; we also tested whether the effects of LPS could be modulated by treatment with rapamycin (RAP), a specific mTOR inhibitor. We determined, in specific rat brain areas, levels of p-mTOR/p-p70S6K and also p-AKT/p-AMPK as downstream or upstream indicators of mTOR activity and tested the effects of LPS and RAP co-administration. Changes in the brain levels of pro-inflammatory cytokines IL-1β and TNF-α and their relative mRNA expression levels were measured, and the involvement of nuclear factor-κB (NF-κB) was also examined in vitro. We confirmed that RAP inhibits the aggravation of absence seizures and depressive-like/sickness behavior induced by LPS in the WAG/Rij rats through the activation of mTOR and show that this effect is correlated with the ability of RAP to dampen and delay LPS increases in neuroinflammatory cytokines IL-1β and TNF-α, most likely through inhibition of the activation of NF-κB. Our results suggest that such a mechanism could contribute to the antiseizure, antiepileptogenic and behavioral effects of RAP and further highlight the potential therapeutic usefulness of mTOR inhibition in the management of human epilepsy and other neurological disorders. Furthermore, we show that LPS-dependent neuroinflammatory effects are also mediated by a

  9. [Nail involvement in leprosy].

    Science.gov (United States)

    Belinchón Romero, I; Ramos Rincón, J M; Reyes Rabell, F

    2012-05-01

    Leprosy, a disease caused by Mycobacterium leprae, primarily affects the skin and nerves, but the nails are also involved in as many as 3 out of 4 patients .The factors that trigger nail changes in leprosy are numerous and include repeated trauma, neuropathy, vascular impairment, infections, lepra reactions, and the drugs used to manage the disease. The changes most often reported include subungual hematomas, onycholysis, onychauxis, onychogryphosis, pterygium unguis, and onychoheterotopia, most of which can be attributed to nerve damage and trauma. Furthermore, the acro-osteolysis that occurs in the advanced stages of the disease may present with brachyonychia, racquet nails, or even anonychia. Infections of the nail bed leading to paronychia and onychomycosis should also be taken into account in leprosy. Other typical changes include longitudinal striae, pitting, macrolunula, Terry nails, leukonychia, hapalonychia, and Beau lines. In this review, we describe the principal nail changes associated with leprosy. These changes, which are highly varied and diverse in origin, are in fact a reflection of the significant morbidity caused by M. leprae infection.

  10. Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease

    Science.gov (United States)

    2012-01-01

    Background Several recent studies have shown that angiotensin type 1 receptor (AT1) antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ). PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions. Methods We have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers) provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662. Results We observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co-administration of GW9662

  11. Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Garrido-Gil Pablo

    2012-02-01

    Full Text Available Abstract Background Several recent studies have shown that angiotensin type 1 receptor (AT1 antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ. PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions. Methods We have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662. Results We observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co

  12. Multidrug toxicity involving sumatriptan.

    Science.gov (United States)

    Knittel, Jessica L; Vorce, Shawn P; Levine, Barry; Hughes, Rhome L; Bosy, Thomas Z

    2015-01-01

    A multidrug fatality involving sumatriptan is reported. Sumatriptan is a tryptamine derivative that acts at 5-HT(1B/1D) receptors and is used for the treatment of migraines. The decedent was a 21-year-old white female found dead in bed by her spouse. No signs of physical trauma were observed and a large number of prescription medications were discovered at the scene. Toxicological analysis of the central blood revealed sumatriptan at a concentration of 1.03 mg/L. Following therapeutic dosing guidelines, sumatriptan concentrations do not exceed 0.095 mg/L. Sumatriptan was isolated by solid-phase extraction and analyzed using liquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode. A tissue distribution study was completed with the following concentrations measured: 0.61 mg/L in femoral blood, 0.56 mg/L in iliac blood, 5.01 mg/L in urine, 0.51 mg/kg in liver, 3.66 mg/kg in kidney, 0.09 mg/kg in heart, 0.32 mg/kg in spleen, 0.01 mg/kg in brain, 15.99 mg/kg in lung and 78.54 mg/45 mL in the stomach contents. Carisoprodol, meprobamate, fluoxetine, doxylamine, orphenadrine, dextromethorphan and hydroxyzine were also present in the blood at the following concentrations: 3.35, 2.36, 0.63, 0.19, 0.06, 0.55 and 0.16 mg/L. The medical examiner ruled the cause of death as acute mixed drug toxicity and the manner of death as accident.

  13. Charmless B decays involving baryons

    Science.gov (United States)

    Gronau, Michael; Rosner, Jonathan L.

    1988-02-01

    Predictions are made for the fraction of B-meson decays involving specific final states of NN¯+nπ (n>=0), as functions of (a) decay dynamics, (b) models for multipion production, (c) the isospin of the final state, and (d) the ratio ||Vbu/Vbc|| of Kobayashi-Maskawa matrix elements. From recent observations of B+-->pp¯π+(+c.c.) and B0-->pp¯π+π- by the ARGUS Collaboration, it is concluded that ||Vbu/Vbc||>~0.08, similar to the ARGUS Collaboration's own estimate of 0.07. However, a more likely value for this ratio is near its present experimental upper limit. Predictions are made for further final states in NN¯+nπ and in other charmless B decays. We also comment briefly on prospects for observing CP violation in B-->NN¯+nπ.

  14. Degree of multicollinearity and variables involved in linear dependence in additive-dominant models Grau de multicolinearidade e variáveis envolvidas na dependência linear em modelos aditivo-dominantes

    Directory of Open Access Journals (Sweden)

    Juliana Petrini

    2012-12-01

    Full Text Available The objective of this work was to assess the degree of multicollinearity and to identify the variables involved in linear dependence relations in additive-dominant models. Data of birth weight (n=141,567, yearling weight (n=58,124, and scrotal circumference (n=20,371 of Montana Tropical composite cattle were used. Diagnosis of multicollinearity was based on the variance inflation factor (VIF and on the evaluation of the condition indexes and eigenvalues from the correlation matrix among explanatory variables. The first model studied (RM included the fixed effect of dam age class at calving and the covariates associated to the direct and maternal additive and non-additive effects. The second model (R included all the effects of the RM model except the maternal additive effects. Multicollinearity was detected in both models for all traits considered, with VIF values of 1.03 - 70.20 for RM and 1.03 - 60.70 for R. Collinearity increased with the increase of variables in the model and the decrease in the number of observations, and it was classified as weak, with condition index values between 10.00 and 26.77. In general, the variables associated with additive and non-additive effects were involved in multicollinearity, partially due to the natural connection between these covariables as fractions of the biological types in breed composition.O objetivo deste trabalho foi avaliar o grau de multicolinearidade e identificar as variáveis envolvidas na dependência linear em modelos aditivo-dominantes. Foram utilizados dados de peso ao nascimento (n=141.567, peso ao ano (n=58.124 e perímetro escrotal (n=20.371 de bovinos de corte compostos Montana Tropical. O diagnóstico de multicolinearidade foi baseado no fator de inflação de variância (VIF e no exame dos índices de condição e dos autovalores da matriz de correlações entre as variáveis explanatórias. O primeiro modelo estudado (RM incluiu o efeito fixo de classe de idade da mãe ao parto e

  15. Combinatorial model and algorithm involving OD distribution and stochastic user equilibrium assignment%OD分布与随机均衡分配的组合模型及算法

    Institute of Scientific and Technical Information of China (English)

    周溪召

    2001-01-01

    Because the randomness of transportation information has not been considered in present practical transportation planning ,the accuracy or efficiency of transportation planning is depreciated.In order to overcome this drawback,the combinatorial model simulaneously involving OD distribution of trips in a transportation network and stochastic user equilibrium assignment(SUEA) of trips to routes in each OD pairs was developped on the basis of analysis on random ness in choices of route and destination for a given mode. It was proved that the solution of the combinatorial model was unique and it satisfied Wardropian principle of SUEA and requirement of OD distribution by introducing Langrangian function.Finally,the algorithm of model was given by using the direction hunting method.%目前交通规划实践缺乏考虑交通信息的随机性,从而降低了它所得结果的准确性.为此,通过分析出行路径选择和目标选择的随机性,建立了交通网络OD分布与随机平衡(或均衡)分配的组合模型,通过引入拉格朗日函数,证明了模型最优解满足随机用户平衡条件和OD分布的要求且最优解是唯一的;最后给出了模型的方向搜索算法.

  16. Dimensionality and Measure of Stereotype Content Model and Ifluence of Involvement%刻板印象内容模型的确认、测量及卷入的影响

    Institute of Scientific and Technical Information of China (English)

    管健; 程婕婷

    2011-01-01

    目的:采用实证研究的方法,对中国大陆群体的刻板印象内容模型和系统模型进行确认、测量,并检验心理卷入是否影响刻板印象改变.方法:预研究通过125名被试的开放式问卷收集典型群体32个,研究一通过103份有效问卷获得群体刻板印象内容模型;研究二通过112份有效问卷探索卷入对于模型改变的影响.结果:①刻板印象内容模型在中国大陆具有较好的信度和效度;②32个群体可以通过热情和能力维度聚类为四个群体类别;③以农民工群体为例,其刻板印象是混合的;④心理卷入对刻板印象内容模型具有较大影响.结论:刻板印象内容模型对中国群体有很好的预测作用,心理卷入程度改变模型的静态性.%Objective: The present research, consisting of a pilot study and two co-relational studies, investigated how stereotypes and emotions shaped behavioral tendencies toward groups, offering convergent support for the behaviors from inter-group affect and stereotypes map framework. Methods: Pilot Study (N=125) and study 1 (N=103) began with SCM questionnaire to explore Chinese participants' content stereotype in 32 groups. Study 2 (N=112) tested the effects of priming the relationship involvement. Results: ①The results indicated that the Chinese SCM questionnaire was acceptable, 2 primary dimensions of SCM were competence and warmth; ②32 groups were clustered in 4 different types; ③In the 32 groups, combinations of warmth and competence generated emotions of admiration, envy, pity, and disgust; ④When the subjects were involved, two models of inter-group bias; SCM and BIAS map were changed. Conclusion: This research provides empirical support for Chinese stereotype contents, which result from perceived structural relations, in predicting behavioral tendencies. And then, the study pointed to the stereotype change possibility under priming the relationship involvement.

  17. Cyclophosphamide cystitis as a model of visceral pain in rats: model elaboration and spinal structures involved as revealed by the expression of c-Fos and Krox-24 proteins.

    Science.gov (United States)

    Lantéri-Minet, M; Bon, K; de Pommery, J; Michiels, J F; Menétrey, D

    1995-01-01

    petechial hemorrhage. Simple chorionic edema was observed from 30 min to 3 h postinjection, but with a progressive increase in severity over time. Edema accompanied by epithelial abrasion was observed for animals that survived 3-4 h postinjection; complete inflammation was observed in animals that survived 4-5 h postinjection. The study of c-Fos- and Krox-24-encoded protein expression demonstrated that few lumbosacral spinal areas were specifically involved in the processing of visceral inputs in response to bladder stimulation. These areas were the parasympathetic column (SPN), the dorsal gray commissure (DGC as the caudal extent of lamina X), and superficial layers of the dorsal horn.(ABSTRACT TRUNCATED AT 400 WORDS)

  18. Drug hypersensitivity reactions involving skin.

    Science.gov (United States)

    Hausmann, Oliver; Schnyder, Benno; Pichler, Werner J

    2010-01-01

    Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely skin involvement to fulminant systemic diseases which may be fatal. Immunohistochemical and functional studies of drug-specific T cells in patients with delayed reactions confirmed a predominant role for T cells in the onset and maintenance of immune-mediated delayed drug hypersensitivity reactions (type IV reactions). In these reactions, drug-specific CD4+ and CD8+ T cells are stimulated by drugs through their T cell receptors (TCR). Drugs can stimulate T cells in two ways: they can act as haptens and bind covalently to larger protein structures (hapten-carrier model), inducing a specific immune response. In addition, they may accidentally bind in a labile, noncovalent way to a particular TCR of the whole TCR repertoire and possibly also major histocompatibility complex (MHC)-molecules - similar to their pharmacologic action. This seems to be sufficient to reactivate certain, probably in vivo preactivated T cells, if an additional interaction of the drug-stimulated TCR with MHC molecules occurs. The mechanism was named pharmacological interaction of a drug with (immune) receptor and thus termed the p-i concept. This new concept may explain the frequent skin symptoms in drug hypersensitivity to oral or parenteral drugs. Furthermore, the various clinical manifestations of T cell-mediated drug hypersensitivity may be explained by distinct T cell functions leading to different clinical phenotypes. These data allowed a subclassification of the delayed hypersensitivity reactions (type IV) into T cell reactions which, by releasing certain cytokines and chemokines, preferentially activate and recruit

  19. Modelo Empírico, Descriptivo y Predictivo Para el Compromiso de Identidad en el Chat en Adolescentes Escolares Chilenos Empirical, Descriptive and Predictive Model for Identity Involvement in Chat use by Chilean School Adolescents

    Directory of Open Access Journals (Sweden)

    María Paz Altuzarra

    2007-11-01

    Full Text Available Se desarrolla un modelo empírico, descriptivo y predictivo de regresión múltiple de las relaciones entre compromiso de identidad en el Chat y salud mental, sexo, curso y tipo de Chat en una muestra de 385 alumnos de ambos sexos, de I, II, III y IV Medio de tres colegios de Santiago de Chile. Se aplicó un cuestionario sobre uso de Internet, Escala de Compromiso de Identidad en el Chat y Cuestionario de Salud Mental en la Edad Juvenil. Se encontró que tanto la salud mental como el tipo de Chat predecían el compromiso de la identidad en el Chat. Se observó un mayor compromiso entre jóvenes mujeres de I y II Medio y que empleaban Chat abierto o mixto.An empirical descriptive and predictive model of multiple regression on the relationships between identity involvement in the Chat and mental health, sex, grade and modality of Chat in a sample of 385 male and female high school students, from Santiago de Chile, is presented. The instruments used were: a questionnaire about Internet usage, an Identity Compromise Scale in the Chat and a Youth Mental Health Scale. Results indicate that both, mental health and type of Chat, predicted compromise of identity in the Chat. It was observed a greater compromise among female teenagers from 9th and 10th grade who used open and mixed Chat.

  20. Cardioprotective effects of the novel Na+/H+ exchanger-1 inhibitor KR-32560 in a perfused rat heart model of global ischemia and reperfusion: Involvement of the Akt-GSK-3beta cell survival pathway and antioxidant enzyme.

    Science.gov (United States)

    Jung, In-Sang; Lee, Sung-Hun; Yang, Min-Kyu; Park, Jung-Woo; Yi, Kyu-Yang; Yoo, Sung-Eun; Kwon, Suk-Hyung; Chung, Hun-Jong; Choi, Wahn-Soo; Shin, Hwa-Sup

    2010-08-01

    To investigate the cardioprotective effects and mechanism of action of KR-32560 {[5-(2-methoxy-5-fluorophenyl)furan-2-ylcarbonyl]guanidine}, a newly synthesized NHE-1 inhibitor, we evaluated the effects of KR-32560 on cardiac function in a rat model of ischemia/reperfusion (I/R)-induced heart injury as well as the role antioxidant enzymes and pro-survival proteins play these observed effects. In isolated rat hearts subjected to 25 min of global ischemia followed by 30 min of reperfusion, KR-32560 (3 and 10 microM) significantly reversed the I/Rinduced decrease in left ventricular developed pressure and increase in left ventricular enddiastolic pressure. In rat hearts reperfused for 30 min, KR-32560 (10 microM) significantly decreased the malondialdehyde content while increasing the activities of both glutathione peroxidase and catalase, two important antioxidant enzymes. Western blotting analysis of left ventricles subjected to I/R showed that KR-32560 significantly increased phosphorylation of both Akt and GSK-3beta in a dose-dependent manner, with no effect on the phosphorylation of eNOS. These results suggest that KR-32560 exerts potent cardioprotective effects against I/Rinduced rat heart injury and that its mechanism involves antioxidant enzymes and the Akt-GSK-3beta cell survival pathway.

  1. Intergenerational Relationship Quality, Gender, and Grandparent Involvement

    Science.gov (United States)

    Barnett, Melissa A.; Scaramella, Laura V.; Neppl, Tricia K.; Ontai, Lenna; Conger, Rand D.

    2010-01-01

    This prospective, intergenerational study (N = 181) considered how parent (G1, Generation 1) and child (G2, Generation 2) relationship quality during adolescence and adulthood is associated with G1's level of involvement with their 3- to 4-year-old grandchildren (G3, Generation 3). Path model analyses indicated different patterns of results for…

  2. Sacroiliac joint involvement in psoriasis.

    Science.gov (United States)

    Kaçar, Cahit; Sezer, Ilhan; Kocabaş, Hilal; Cay, Hasan Fatih; Cevikol, Can; Alpsoy, Erkan; Melikoğlu, Meltem Alkan; Akman, Ayşe

    2010-07-01

    Psoriasis is a skin disorder that is associated with arthritis. Sacroiliac joint involvement is considered to be less frequent than the other types of psoriatic arthritis. Additionally, the psoriatic sacroiliitis is considered to be asymmetric in general. We aimed to define the frequency and type of sacroiliac involvement in patients with psoriasis. Patients with psoriasis were included the study. Characteristics of skin, nail and articular involvement were noted. Psoriasis area and severity index was calculated. Antero-posterior pelvic X-rays were obtained and graded by two rheumatologists and a radiologist independently. One hundred and thirty-three patients were included. Thirty-seven of patients (27%) have articular involvement symptomatically. The sacroiliac joint involvement was observed in 34 (26%) of patients. More than one-half of sacroiliac involvement was bilateral while less than one-half was in symptomatic patients regarding sacroiliitis. Fifty-seven percentages of all patients have psoriatic nail involvement. Sacroiliac joint involvement did not show any significant association with psoriatic nail involvement or the severity of skin disease. We found higher frequency of sacroiliac joint involvement and bilateral sacroiliitis in patients with psoriasis. This is in contrast to present information about the association of psoriasis and sacroiliitis. These findings need confirmation by further studies and with more sophisticated techniques such as magnetic resonance imaging.

  3. INVOLVEMENT

    Directory of Open Access Journals (Sweden)

    Yeşim ULUSU

    2016-01-01

    Full Text Available The concept of “Involvement” is based on social psychology and specially attitude and attitude change subjects in the area of persuasive communication. The conceptualization of the “involvement” as a phe- nomenon was started to construct especially during the years between 1965-1980 when “involvement” was discussed in many areas of social sciences related to human behavior such as marketing, consumer behavior and advertising with its different dimensions.

  4. INVOLVEMENT

    OpenAIRE

    ULUSU, Yeşim

    2016-01-01

    The concept of “Involvement” is based on social psychology and specially attitude and attitude change subjects in the area of persuasive communication. The conceptualization of the “involvement” as a phe- nomenon was started to construct especially during the years between 1965-1980 when “involvement” was discussed in many areas of social sciences related to human behavior such as marketing, consumer behavior and advertising with its different dimensions.

  5. Monoarticular Hip Involvement in Pseudogout

    Directory of Open Access Journals (Sweden)

    Figen Kocyigit

    2015-01-01

    Full Text Available Pseudogout is the acutest form of arthritis in the elderly. Although clinical manifestations vary widely, polyarticular involvement is typical mimicking osteoarthritis or rheumatoid arthritis. Monoarticular involvement is relatively rare and is generally provoked by another medical condition. There are reported cases of hip involvement by pseudogout in monoarticular form. However, all of the cases were presented as septic arthritis. In this report, we present a case of monoarticular hip involvement mimicking soft tissue abscess. We confirmed the pseudogout diagnosis after ultrasonographic evaluation of the involved hip joint and pathological and biochemical analysis of synovial fluid analysis. Diagnosis is important to avoid unnecessary medical and surgical treatment in cases of the bizarre involvement of hip in pseudogout.

  6. Skin involvement in Dupuytren's disease.

    OpenAIRE

    Wade, R.; Igali, L; Figus, A

    2016-01-01

    Whether the palmar skin has a role in the development, propagation or recurrence of Dupuytren's disease remains unclear. Clinical assessment for skin involvement is difficult and its correlation with histology uncertain. We prospectively biopsied the palmar skin of consecutive patients undergoing single digit fasciectomy (for primary Dupuytren's disease without clinically involved skin) and dermofasciectomy (for clinically involved skin or recurrence) in order to investigate this relationship...

  7. Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside in the MPTP-induced mouse model of Parkinson's disease: Involvement of reactive oxygen species-mediated JNK, P38 and mitochondrial pathways.

    Science.gov (United States)

    He, Hong; Wang, Songhai; Tian, Jiyu; Chen, Lei; Zhang, Wei; Zhao, Junjie; Tang, Haifeng; Zhang, Xiaojun; Chen, Jianzong

    2015-11-15

    Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress-induced neuron loss is thought to play a crucial role in the pathogenesis of PD. Previous work from our group suggests that 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from a traditional Chinese herb, Polygonum multiflorum thunb, can attenuate 1-methyl-4-phenyl pyridium-induced apoptosis in the neuronal cell line PC12, by inhibiting reactive oxygen species generation and modulating c-Jun N-terminal kinases (JNK) activation. Here, we investigated the protective effects of TSG against 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-induced loss of tyrosine hydroxylase positive cells in mice and the underlying mechanisms. The results showed that MPTP-induced loss of tyrosine hydroxylase positive cells and reactive oxygen species generation were prevented by TSG in a dose-dependent manner. The reactive oxygen species scavenger N-acetylcysteine could also mitigate reactive oxygen species generation. Moreover, JNK and P38 were activated by MPTP, but extracellular signal-regulated protein kinases phosphorylation did not change after MPTP treatment. TSG at different doses blocked the activation of JNK and P38. The protective effect of TSG was also associated with downregulation of the bax/bcl-2 ratio, reversed the release of cytochrome c and smac, and inhibited the activation of caspase-3, -6, and -9 induced by MPTP. In conclusion, our studies demonstrated that the protective effects of TSG in the MPTP-induced mouse model of PD are involved, at least in part, in controlling reactive oxygen species-mediated JNK, P38, and mitochondrial pathways.

  8. Citizen Involvement in Public Television.

    Science.gov (United States)

    Wenner, Lawrence A.

    The purpose of this study was to evaluate the amount and quality of citizen involvement in public television. From the perspective of the "average citizen," the concept of involvement is considered with regard to the Carnegie Commission, the Corporation for Public Broadcasting (CPB) borad of directors, the National Citizens Committee for…

  9. Preparing Teachers for Parent Involvement.

    Science.gov (United States)

    Safran, Daniel

    This paper examines the potential impact of parent involvement in the formal education of their children and suggests ways that teacher education can be restructured to prepare teachers to work with parents. This paper attempts to answer five questions: (1) Why should parents be involved in the formal education of their children? (2) Why should…

  10. Parental Involvement and Academic Achievement

    Science.gov (United States)

    Goodwin, Sarah Christine

    2015-01-01

    This research study examined the correlation between student achievement and parent's perceptions of their involvement in their child's schooling. Parent participants completed the Parent Involvement Project Parent Questionnaire. Results slightly indicated parents of students with higher level of achievement perceived less demand or invitations…

  11. Involvement of inositol in reproduction.

    NARCIS (Netherlands)

    Beemster, P.; Groenen, P.; Steegers-Theunissen, R.P.M.

    2002-01-01

    Inositol is involved in several aspects of reproduction. It affects overall embryogenesis, may prevent neural tube defects, and stimulates the production of lung surfactant. This article will review the involvement of inositol in reproduction. After describing the biologic function of inositol and i

  12. Direct Employee Involvement Quality (DEIQ)

    NARCIS (Netherlands)

    Torka, Nicole; Woerkom, van Marianne; Looise, Jan-Kees

    2008-01-01

    This paper focuses on one aspect of human resource management (HRM) that is important for innovative employee behaviour: direct employee involvement quality (DEIQ). However, research has also shown that employee involvement is often in serious need of improvement. This paper presents evidence from t

  13. Parental Involvement and Academic Achievement

    Science.gov (United States)

    Goodwin, Sarah Christine

    2015-01-01

    This research study examined the correlation between student achievement and parent's perceptions of their involvement in their child's schooling. Parent participants completed the Parent Involvement Project Parent Questionnaire. Results slightly indicated parents of students with higher level of achievement perceived less demand or invitations…

  14. Creating Learning at Conferences Through Participant Involvement

    DEFF Research Database (Denmark)

    Ravn, Ib; Elsborg, Steen

    in Denmark to introduce a variety of simple learning techniques related to the design principles at thirty real conferences of some 100-200 participants each. We present twelve of these techniques and the data evaluating them and conclude that by spending a fraction of the time at a conference on involving......The typical conference is brimming with PowerPoint presentations that leave very little time for participant involvement. Students of learning have long abandoned the transfer model that underlies this massive show of one-way communication. We propose an alternative theory of the conference...... as a forum for learning, mutual inspiration and "human co-flourishing." We offer five design principles that specify how conferences may involve participants more and hence increase their learning. In the research and development effort reported here, our team collaborated with conference organizers...

  15. Ocular involvement in pemphigus vulgaris.

    Science.gov (United States)

    Akhyani, Maryam; Keshtkar-Jafari, Alireza; Chams-Davatchi, Cheyda; Lajevardi, Vahide; Beigi, Sara; Aghazadeh, Nessa; Rayati Damavandi, Maede; Arami, Shabnam

    2014-07-01

    Pemphigus vulgaris (PV) is an autoimmune disorder affecting the skin and mucous membranes. Ocular involvement in PV has been reported but its prevalence and clinical characteristics are not well defined. This prospective cross-sectional study of 103 PV patients was designed to determine the prevalence, clinical types and epidemiological trends of ocular involvement in a population of Iranian patients with PV. Ocular involvement was present in 17 (16.5%) patients. Conjunctivitis was the most prevalent type of ocular involvement (9/17, 52.9%), followed by erosion of the palpebral conjunctiva (7/17, 41.2%). Erosion of the bulbar conjunctiva was noted in only one patient (5.9%). The most commonly reported symptoms were eye irritation (76.5%) and redness (76.5%). No significant relation was found between ocular involvement and disease activity (partial remission or relapse). Mucoid discharge was significantly more common in patients with conjunctival erosions as compared to patients with conjunctivitis (P = 0.038). We conclude that ocular involvement is not rare in PV; 16.5% of PV patients develop ocular disease independent of the disease activity and extension. Conjunctivitis is the most common type of involvement, however, palpebral conjunctival erosion is more frequent than previously realized.

  16. Road rage and collision involvement.

    Science.gov (United States)

    Mann, Robert E; Zhao, Jinhui; Stoduto, Gina; Adlaf, Edward M; Smart, Reginald G; Donovan, John E

    2007-01-01

    To assess the contribution of road rage victimization and perpetration to collision involvement. The relationship between self-reported collision involvement and road rage victimization and perpetration was examined, based on telephone interviews with a representative sample of 4897 Ontario adult drivers interviewed between 2002 and 2004. Perpetrators and victims of both any road rage and serious road rage had a significantly higher risk of collision involvement than did those without road rage experience. This study provides epidemiological evidence that both victims and perpetrators of road rage experience increased collision risk. More detailed studies of the contribution of road rage to traffic crashes are needed.

  17. Revisiting the Role of Interleukin-1 Pathway in Osteoarthritis: Interleukin-1α and -1β, and NLRP3 Inflammasome Are Not Involved in the Pathological Features of the Murine Menisectomy Model of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Sonia Nasi

    2017-06-01

    Full Text Available Background: Innate immune response components such as toll-like receptors (TLRs and NLRP3-inflammasome act in concert to increase IL-1α/β secretion by synovial macrophages. Previous results suggest that IL-1α/β could be an important mediator involved in the pathogenesis of osteoarthritis (OA.Objectives: The aim of our study was to evaluate the role of NLRP3, IL-1β, and IL-1α in the menisectomy (MNX model of murine OA.Methods: Murine chondrocytes (CHs and bone marrow-derived machrophages (BMDM were stimulated with hydroxyapatite (HA crystals, a form of calcium-containing crystal found in human OA, and IL-1β and IL-6 secretion assayed by ELISA.Conversely, the ability of IL-1β and IL-6 to induce CHs calcification was assessed in vitro by Alizarin red staining. Knees from 8 to 10 weeks old C57Bl/6J wild-type (WT (n = 7, NLRP3−/− (n = 9, IL-1α−/− (n = 5, and IL-1β−/− (n = 5 mice were menisectomized, using the sham-operated contralateral knee as control. 8 weeks later, knee cartilage degradation and synovial inflammation were evaluated by histology. In addition, apoptotic chondrocytes, metalloproteases activity, and collagen-type 2 expression were evaluated in all mice. Joint calcification and subchondral bone parameters were quantified by CT-scan in WT and IL-1β−/− menisectomized knees.Results:In vitro, HA crystals induced significant increased IL-6 secretion by CHs, while IL-1β remained undetectable.Conversely, both IL-6 and IL-1β were able to increase chondrocytes mineralization. In vivo, operated knees exhibited OA features compared to sham-operated knees as evidenced by increased cartilage degradation and synovial inflammation. In menisectomized KO mice, severity and extent of cartilage lesions were similar (IL-1α−/− mice or exacerbated (IL-1β−/− and NLRP3−/− mice compared to that of menisectomized WT mice. Metalloproteases activity, collagen-type 2 expression, chondrocytes apoptosis, and synovial

  18. 武汉城市圈政策网络治理:参与主体与治理模式%Policy Network in Wuhan Metropolis: Participants Involvement and Governance Models

    Institute of Scientific and Technical Information of China (English)

    余军华; 吕丽娜

    2012-01-01

    The purpose of developing Wuhan metropolis is to enhance regional competitiveness in mid-China as part of plan for rise of central China. Local governments between this metropolitan area who are much fragmented, however, have respective jurisdiction interest which result in goal conflict and coordination dilemma. The method to coordinate such interests' conflicts through higher-level government should increase the administrative costs, and can not change the fundamental interest demands. In addition, the complexity of public affairs in metropolis and development of the social self-organization mechanism require a bottom-up distributing of power. Network governance proved an efficient solution to these problems by practice of west countries can be used to explore how to handle the cooperation issue in this paper. After main literature review in net-work governance area, four governance models targeting at Wuhan metropolis are designed: (1)as to regional plan policy, it should be government-centered and participants should be less; (2)as for policies involved in public goods, private firms and non-profit organizations should take part in decision-making and be guided by governments; (3)policies about production of private commodities should mainly decided by private and nor-profit organizations, government steering; (4)policies decision- making about the peoples' livelihood should follow citizens' will and be taken bottom-up decision model.%武汉城市圈的发展既是提升区域竞争力的需要,也是中部崛起的中坚力量。但是,城市圈内各地方政府机构分属不同的行政区划,形成了版图利益的冲突。这种利益冲突通过更高一级的政府来协调,行政成本巨大,而且改变不了根本的利益诉求。此外,城市圈公共事务的复杂性和社会自组织机制的发展要求一种自下而上的权力分配格局。面对这种难题,经过国外大量实践证实的政策网络治理理论

  19. User involvement and the NHS reforms.

    Science.gov (United States)

    Rhodes, Penny; Nocon, Andrew

    1998-11-01

    The policy of 'user involvement' in the UK National Health Service emerged during the 1990s along with the reforms that created an internal market. Despite the official rhetoric, progress has been limited. Critics suggest that, not only was the policy flawed in its conception by the construction of service users as consumers and the conflation of consumerism with empowerment, but collaborative models of involvement have tended to legitimate rather than challenge existing provision. Some commentators have questioned the value of user involvement initiatives and proposed that alternative approaches, such as a strengthening of procedural rights or alignment with broader political campaigns, would be more appropriate. The low prominence given in the recent Government White Paper The New NHS1 to the contribution of service users, however, represents less of an ideological shift than a concentration on other, in the Government's view, more pressing priorities: namely, a concern to address the problems of public legitimacy and low staff morale by engaging in greater public participation and giving health professionals a more central role. The result has been a weakening of the users' voice by a conflation of user involvement with public participation and giving health professionals the authority to define users' needs for them. Service users risk, not only having their contribution devalued, but losing the right to an independent and distinctive voice. There is a real danger that the issues of user involvement will not be included on local agendas and the disparities between provision and need and between professionals' and users' views will increase.

  20. Third party involvement in barroom conflicts.

    Science.gov (United States)

    Parks, Michael J; Osgood, D Wayne; Felson, Richard B; Wells, Samantha; Graham, Kathryn

    2013-01-01

    This study examines the effect of situational variables on whether third parties intervene in conflicts in barroom settings, and whether they are aggressive or not when they intervene. Based on research on bystander intervention in emergencies, we hypothesized that third parties would be most likely to become involved in incidents with features that convey greater danger of serious harm. The situational variables indicative of danger were severity of aggression, whether the aggression was one-sided or mutual, gender, and level of intoxication of the initial participants in the conflict. Analyses consist of cross-tabulations and three-level Hierarchical Logistic Models (with bar, evening, and incidents as levels) for 860 incidents of verbal and physical aggression from 503 nights of observation in 87 large bars and clubs in Toronto, Canada. Third party involvement was more likely during incidents in which: (1) the aggression was more severe; (2) the aggression was mutual (vs. one-sided) aggression; (3) only males (vs. mixed gender) were involved; and (4) participants were more intoxicated. These incident characteristics were stronger predictors of non-aggressive third party involvement than aggressive third party involvement. The findings suggest that third parties are indeed responding to the perceived danger of serious harm. Improving our knowledge about this aspect of aggressive incidents is valuable for developing prevention and intervention approaches designed to reduce aggression in bars and other locations. © 2013 Wiley Periodicals, Inc.

  1. [Hand involvement in systemic sclerosis].

    Science.gov (United States)

    Mouthon, Luc

    2013-12-01

    Hand involvement is very common in patients with systemic sclerosis and represents an important tool for the early diagnosis of the disease. Vascular involvement of the hands is at the forefront of systemic sclerosis, with Raynaud's phenomenon, which may be complicated by digital ulcers, digital necrosis causing pain, infection and significant disability. Joint inflammation can also be disabling and causes the occurrence of contractures and deformities resulting in a marked hand disability. Skin sclerosis involving fingers and hands leads to the occurrence of pain and functional impairment. Hand involvement contributes to 75 % of global disability in patients with systemic sclerosis. Only a comprehensive care, taking into account the vascular, skin and joint manifestations, including physical therapy if needed can improve hand function in patients with systemic sclerosis.

  2. Abdominal Actinomycetoma With Lymphnode Involvement

    Directory of Open Access Journals (Sweden)

    Damisetty Rajetha

    2004-01-01

    Full Text Available Actinomycotic mycetoma of the anterior abdominal wall with inguinal lymphnode involvement, an exceedingly rare entity is described here with mycological histological features. Remarkable therapeutic response was noted with Welsh regimen.

  3. User Involvement And Entrepreneurial Action

    Directory of Open Access Journals (Sweden)

    Eva Heiskanen

    2007-01-01

    Full Text Available Involving users in the innovation process is a subject of much research, experimentation, and debate. Less attention has been given to the limits to user involvement that ensue from specific organizational characteristics. This article explores barriers to the utilization of users’ input in two small companies developing interactive digital applications. We contrast our findings to earlier research involving large companies to identify features of entrepreneurial sensemaking and action that influence the utilization of users’ input. We find that the small companies follow a distinct action rationality, leading to rapid implementation of some user inputs, and defensiveness toward others. Both sets of data also reveal common features that are often overlooked in the literature. We reconceptualize user involvement as a form of interaction between users and innovating companies that is facilitated and constrained by micro-sociological processes, on the one hand, and the nature of the competitive environment, on the other.

  4. Patient involvement in hospital architecture

    DEFF Research Database (Denmark)

    Herriott, Richard

    2017-01-01

    This paper examines user-involvement in the process used to design new hospitals. Denmark is in the midst of a phase of hospital building. This recent experience is studied by means of expert interviews with senior practitioners involved in three projects. Examined thematically, the data covers......-studied area, design for hospitals. It highlights difficulties in applying the goals of user-centred design and Design for All in large projects....

  5. Innovative Pedagogical Processes Involving Educational Technology

    DEFF Research Database (Denmark)

    Weitze, Charlotte Lærke

    it experimented with gamified learning designs. This involved the students designing digital games while implementing learning goals from their curriculum. The project thus created knowledge about which learning designs and competence development models were possible in this environment, which learning designs...... about how design and learning processes can support continuous pedagogical innovation and competence development. The objective of the learning designs was to create motivating learning experiences for the students in the hybrid synchronous video-mediated learning environment, to which end...

  6. Observed Changes in the Alertness and Communicative Involvement of Students with Multiple and Severe Disability Following In-Class Mentor Modelling for Staff in Segregated and General Education Classrooms

    Science.gov (United States)

    Foreman, P.; Arthur-Kelly, M.; Bennett, D.; Neilands, J.; Colyvas, K.

    2014-01-01

    Background: The improvement of engagement and involvement in communicative and socially centred exchanges for individuals with multiple and severe disability (MSD) presents complex and urgent challenges to educators. This paper reports the findings of an intervention study designed to enhance the interactive skills of students with MSD using an…

  7. User involvement in care work

    DEFF Research Database (Denmark)

    Dybbroe, Betina; Kamp, Annette

    effectiveness and shared responsibility for care pathways. While NPM position users as consumers making their free choice, the user involvement paradigm underlines the users’ active participation in the mastering of their problems and disease. Research is scarce on this theme, and has until now primarily......In recent years user involvement has become a paradigm for transforming the health and social care sector. This development–also labelled empowerment, co-creation, partnership, patient-centeredness - is seen as a means to reform organizations in ways that enhance quality, economic cost...... addressed the way this paradigm affects the users, in specific sectors. However user involvement also affects working life. It may imply change and redistribution of tasks and identities between users and professionals, and may also transform the relations of care. In this paper we explore the possible...

  8. Strategy Innovation with Employee Involvement

    DEFF Research Database (Denmark)

    Friis, Ole Uhrskov; Koch, Christian

    2015-01-01

    if the managers still dominate, some processes of direct involvement of employees occur, in particular when employees are asked to supplement overall strategic goals and when they directly shape several sub-strategies. Strategy practices found include strategy planning, an open space workshop and organised......The purpose of this article is to investigate how employees can be involved in strategy innovation processes and how new strategy practices (new tools and procedures) are used to change strategy praxis in order to sustain value creation. In the strategizing actions, we found that even...... strategy projects. Especially the latter two are important in facilitating the employee involvement. The case, however, also exhibits enterprise-situated praxises related to unplanned events, like the mitigation of taboos....

  9. Involving Employees in Strategy innovation

    DEFF Research Database (Denmark)

    Friis, Ole Uhrskov; Koch, Christian

    2011-01-01

    some of its employees. Even if managers still dominate, some processes of direct involvement of employees occur. The employees are in particular active in supplementing overall strategic goals and directly shaping one sub strategy, that of ‘process’. Strategy practices include planning, Porterian......Strategy as a practice and continuous innovation approaches are combined to conceptualise dilemmas of short versus long term and to analyse a case of employee participation as a particular example of strategy innovation. The case is a medium size textile company developing its strategy involving...... and Balanced Score Card consultancy, an ‘open space’ workshop and organized strategy projects. Especially the latter two are important in facilitating the employee involvement. The case however also exhibit enterprise situated praxis’s like mitigation of taboos....

  10. Gastrointestinal involvement in systemic sclerosis.

    Science.gov (United States)

    Savarino, Edoardo; Furnari, Manuele; de Bortoli, Nicola; Martinucci, Irene; Bodini, Giorgia; Ghio, Massimo; Savarino, Vincenzo

    2014-10-01

    Systemic sclerosis is an autoimmune chronic disease characterised by microvascular, muscular and immunologic abnormalities that lead to progressive and systemic deposition of connective tissue in the skin and internal organs. The gastrointestinal tract is often overlooked by physicians but it is the most affected organ after the skin, from the mouth to the anus. Indeed, 80% of SSc patients may present with gastrointestinal involvement. Gastrointestinal manifestations range from bloating and heartburn to dysphagia and anorectal dysfunction to severe weight loss and malabsorption. However, the gastrointestinal involvement is rarely the direct cause of death, but has great impact on quality of life and leads to several comorbidities that subsequently affect patients' survival. Treatments, including nutritional support and prokinetics provide limited benefits and do not arrest the progressive course of the disease, but earlier detection of gastrointestinal involvement may reduce the risk of complications such as malnutrition.

  11. [Heel involvement in rheumatoid polyarthritis].

    Science.gov (United States)

    Bouysset, M; Tebib, J G; Vianey, J C; Berthier, M; Nemoz, J C; Chaumentin, G; Schnepp, J; Llorca, G; Bouvier, M

    1990-11-01

    Calcaneus involvement during the course of RA is poorly known. A clinical and radiological study of 408 consecutive rheumatoid feet are then reported. If talalgia was seldomly noted (3.7 p. cent), plantar calcaneitis was found in 29.7 p. cent as plantar spur. Similarly, posterior exostosis was displayed in 30.5 p. cent of patients. These radiological abnormalities are increased in RA but appeared more as a consequence of the statical modification of the foot secondary to RA process than as a direct involvement. Logical orthopedic therapeutics are then proposed.

  12. Multisystem involvement in neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Megan M Langille

    2015-01-01

    Full Text Available We describe a case of pediatric neuromyelitis optica (NMO with muscle and lung involvement in addition to central nervous system disease. Our patient initially presented with features of area postrema syndrome, then subsequently with optic neuritis. The patient also had recurrent hyperCKemia that responded to corticosteroids. Finally, axillary and hilar adenopathy with pulmonary consolidation were noted as well and responded to immunomodulation. Our case highlights multisystem involvement in NMO including non-infectious pulmonary findings which have not been described in the pediatric population previously.

  13. Vertebral osteomyelitis without disc involvement

    Energy Technology Data Exchange (ETDEWEB)

    Kamani, I.; Syed, I.; Saifuddin, A. E-mail: asaifuddin@aol.com; Green, R.; MacSweeney, F

    2004-10-01

    Vertebral osteomyelitis is most commonly due to pyogenic or granulomatous infection and typically results in the combined involvement of the intervertebral disc and adjacent vertebral bodies. Non-infective causes include the related conditions of chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. Occasionally, these conditions may present purely within the vertebral body, resulting in various combinations of vertebral marrow oedema and sclerosis, destructive lesions of the vertebral body and pathological vertebral collapse, thus mimicking neoplastic disease. This review illustrates the imaging features of vertebral osteomyelitis without disc involvement, with emphasis on magnetic resonance imaging (MRI) findings.

  14. Parental Involvement in Norwegian Schools

    Science.gov (United States)

    Paulsen, Jan Merok

    2012-01-01

    This article examines findings on key challenges of school-parent relations in Norway. The review is based on recent large-scale studies on several issues, including formalized school-parent cooperation, parental involvement in the pedagogical discourse, and teacher perspectives on the parents' role in the school community. Findings suggest a…

  15. Parent Involvement as Ritualized Practice

    Science.gov (United States)

    Doucet, Fabienne

    2011-01-01

    This article examines parent involvement (PI) as a ritual system using Turner's concept of root paradigms. Through a twofold analysis, I argue that the highly ritualized nature of PI practices creates a group identity among mainstream parents and schools that marginalizes diverse families. First, I point out three root paradigms in the ritual…

  16. Putaminal involvement in Rasmussen encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Rajesh, Bhagavatheeswaran; Ashalatha, Radhakrishnan [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Neurology, Trivandrum, Kerala (India); Kesavadas, Chandrasekharan; Thomas, Bejoy [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Imaging Sciences and Interventional Radiology, Trivandrum, Kerala (India)

    2006-08-15

    Rasmussen encephalitis (RE) is a rare devastating disease of childhood causing progressive neurological deficits and intractable seizures, typically affecting one hemisphere. Characteristic MRI features include progressive unihemispheric focal cortical atrophy and grey- or white-matter high-signal changes and basal ganglion involvement, particularly of the caudate nucleus. To analyse the pattern of involvement of different brain structures in a series of patients with RE and to attempt clinical correlation. We reviewed the medical records and neuroimaging data of 12 patients diagnosed with RE satisfying the European Consensus Statement diagnostic criteria. The disease manifested as seizures in all patients and was refractory; epilepsia partialis continua was a notable feature (nine patients). Hemiparesis of varying grades was noted in all but one patient; none had extrapyramidal signs. Neuroimaging showed cortical involvement in the insular/periinsular regions in 11 patients. Caudate atrophy was noted in ten patients. Putaminal atrophy was seen in nine patients, six of whom had additional hyperintense signal changes. Our study highlights frequent putaminal atrophy and signal changes in RE, which suggests a more extensive basal ganglion involvement than emphasized previously. Recognition of putaminal changes may be a useful additional tool in the radiological diagnosis of RE. (orig.)

  17. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neur...

  18. Promoting Active Involvement in Classrooms

    Science.gov (United States)

    Conderman, Greg; Bresnahan, Val; Hedin, Laura

    2012-01-01

    This article presents a rationale for using active involvement techniques, describes large- and small-group methods based on their documented effectiveness and applicability to K-12 classrooms, and illustrates their use. These approaches include ways of engaging students in large groups (e.g., unison responses, response cards, dry-erase boards,…

  19. Involving Employees in Strategy innovation

    DEFF Research Database (Denmark)

    Friis, Ole Uhrskov; Koch, Christian

    2011-01-01

    Strategy as a practice and continuous innovation approaches are combined to conceptualise dilemmas of short versus long term and to analyse a case of employee participation as a particular example of strategy innovation. The case is a medium size textile company developing its strategy involving...

  20. Managing Parent Involvement during Crisis

    Science.gov (United States)

    Merriman, Lynette S.

    2008-01-01

    In the wake of 9/11, Hurricane Katrina, and the Virginia Tech shooting tragedy, it is no surprise that concern for students' safety is the primary reason attributed to parents' increased involvement. Parents and university administrators share in their commitment to student safety. However, college and university staff who assume responsibility…

  1. Consumer involvement in oral nutritional supplements purchasing behavior

    Directory of Open Access Journals (Sweden)

    Dwi Meilia Fitriyani

    2017-06-01

    Full Text Available The paper aimed to get insight of consumer involvement in purchasing behavior towards ONS (Oral Nutritional Supplements for children. By implementing an online survey with sample size of 100, the research investigated the factors (motivation and stimulus factor influencing consumer involvement and the causality between consumer involvement with the product knowledge as well as purchasing behavior. The research tool used was a 5-points Likert questionnaire in which respondents were asked to show their agreements about 40 items of 5 constructs. A partial least square - structural equation modeling by Smart-PLS software used to test the model. The results of this research also comes to conclusion that motivation and stimulus factor had significant affects on consumer involvement, consumer involvement had significant influence to product knowledge as well as ONS purchasing behavior, however product knowledge did not have significant affects on purchasing behavior. The results also showed that the product involvement has an important influence on consumers behavior.

  2. Involving Motion Graphics in Spatial Experience Design

    DEFF Research Database (Denmark)

    Steijn, Arthur

    2013-01-01

    process, and therefore it should be constructed as such. Since the development of the design model has this double focus, I involve design students in design laboratories related to my practice as a teacher in visual communication design and production design. I also reflect on how an initial design...... conceptualization of various design elements in an analysis of the way in which these elements are integrated and used in the creation of particular experiences of space, atmosphere and artistic expression. On the basis of this analysis I present a preliminary construction of a design model including some design...... laboratory may be set-up and used. Finally I describe how this design lab can be used as a method for creating both practical knowledge of the manner in which the design model may be applied in actual design processes, as well as how these processes can be used for pointing out design elements or dimensions...

  3. GABAA receptor subtype involvement in addictive behaviour.

    Science.gov (United States)

    Stephens, D N; King, S L; Lambert, J J; Belelli, D; Duka, T

    2017-01-01

    GABAA receptors form the major class of inhibitory neurotransmitter receptors in the mammalian brain. This review sets out to summarize the evidence that variations in genes encoding GABAA receptor isoforms are associated with aspects of addictive behaviour in humans, while animal models of addictive behaviour also implicate certain subtypes of GABAA receptor. In addition to outlining the evidence for the involvement of specific subtypes in addiction, we summarize the particular contributions of these isoforms in control over the functioning of brain circuits, especially the mesolimbic system, and make a first attempt to bring together evidence from several fields to understanding potential involvement of GABAA receptor subtypes in addictive behaviour. While the weight of the published literature is on alcohol dependency, the underlying principles outlined are relevant across a number of different aspects of addictive behaviour. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  4. Multi-Dimensional Parental Involvement in Schools: A Principal's Guide

    Science.gov (United States)

    Rapp, Nicole; Duncan, Heather

    2012-01-01

    Parental involvement is an important indicator of students' success in school. When schools engage families in a manner connected to improving learning, students do make greater gains. Creating and implementing an effective parental involvement model is an essential component in increasing student achievement in school. This article addresses the…

  5. Design for Mass User Involvement

    DEFF Research Database (Denmark)

    Vianello, Giovanna; Tan, Adrian

    as it creates a closer relationship to customers as well as creating the best possibilities for reducing impact of products on our natural environment. This new way of organizing the development process in collaboration with users holds many opportunities, but also challenges for companies and researchers. We...... be broadly adopted by the masses of people in the next century. Design methods are powerful tools to create solutions that fulfill the needs of people and improve their lives. Based on emerging trends in design and development as well as projecting current trends in the world today, we propose a new design...... formalism for the future in 2030 that is suited for a high tech, global manufacturing company. The design formalism involves the user throughout the design process and involves the company in the entire lifecycle of its products. It is believed that this approach will give companies a competitive advantage...

  6. Inclusive Briefing and User Involvement

    DEFF Research Database (Denmark)

    Jensen, Per Anker

    2011-01-01

    includes a literature study on briefing and user involvement in building projects, and presents a case study of a major building project of a new headquarters and media centre for the Danish Broadcasting Corporation in Copenhagen. The building project was actively used as part of a corporate change process......Briefing is not just about specifying needs as requirements but also about evaluating how well design proposals fulfil needs and aspirations. Furthermore, briefing is not only about building design. Briefing starts at the preproject stage to create a basis for the project decision and can include...... a number of different processes with varying purposes before and during the design and construction activities. Thus, briefing can be regarded as a continuous process but it should also be an inclusive and interactive process with the involvement of all stakeholders, including end users. This article...

  7. Inclusive Briefing and User Involvement

    DEFF Research Database (Denmark)

    Jensen, Per Anker

    2011-01-01

    Briefing is not just about specifying needs as requirements but also about evaluating how well design proposals fulfil needs and aspirations. Furthermore, briefing is not only about building design. Briefing starts at the preproject stage to create a basis for the project decision and can include...... a number of different processes with varying purposes before and during the design and construction activities. Thus, briefing can be regarded as a continuous process but it should also be an inclusive and interactive process with the involvement of all stakeholders, including end users. This article...... includes a literature study on briefing and user involvement in building projects, and presents a case study of a major building project of a new headquarters and media centre for the Danish Broadcasting Corporation in Copenhagen. The building project was actively used as part of a corporate change process...

  8. Renal involvement in antiphospholipid syndrome.

    Science.gov (United States)

    Pons-Estel, Guillermo J; Cervera, Ricard

    2014-02-01

    Renal involvement can be a serious problem for patients with antiphospholipid syndrome (APS). However, this complication has been poorly recognized and studied. It can be present in patients who have either primary or systemic lupus erythematosus-associated APS. Clinical and laboratory features of renal involvement in APS include hypertension, hematuria, acute renal failure, and progressive chronic renal insufficiency with mild levels of proteinuria that can progress to nephrotic-range proteinuria. The main lesions are renal artery stenosis, venous renal thrombosis, and glomerular lesions (APS nephropathy) that may be acute (thrombotic microangiopathy) and/or chronic (arteriosclerosis, arterial fibrous intimal hyperplasia, tubular thyroidization, arteriolar occlusions, and focal cortical atrophy). APS can also cause end-stage renal disease and allograft vascular thrombosis. This article reviews the range of renal abnormalities associated with APS, and their diagnosis and treatment options.

  9. Liver involvement in systemic infection

    Institute of Scientific and Technical Information of China (English)

    Masami; Minemura; Kazuto; Tajiri; Yukihiro; Shimizu

    2014-01-01

    The liver is often involved in systemic infections,resulting in various types of abnormal liver function test results.In particular,hyperbilirubinemia in the range of 2-10 mg/dL is often seen in patients with sepsis,and several mechanisms for this phenomenon have been proposed.In this review,we summarize how the liver is involved in various systemic infections that are not considered to be primarily hepatotropic.In most patients with systemic infections,treatment for the invading microbes is enough to normalize the liver function tests.However,some patients may show severe liver injury or fulminant hepatic failure,requiring intensive treatment of the liver.

  10. Lupus panniculitis involving the breast

    Energy Technology Data Exchange (ETDEWEB)

    Sabate, Josep M.; Gomez, Antonio; Torrubia, Sofia; Salinas, Teresa; Clotet, Montse [Universitat Autonoma de Barcelona, Unity of Breast Imaging, Department of Diagnostic Radiology, Hospital de Sant Pau, Barcelona (Spain); Lerma, Enrique [Universitat Autonoma de Barcelona, Department of Pathology, Hospital de Sant Pau, Barcelona (Spain)

    2006-01-01

    Lupus panniculitis is an unusual immunological disease that characteristically affects the subcutaneous fat and occurs in 2% of patients with systemic lupus erythematosus. We report a case of lupus panniculitis involving the breast, which represents a very uncommon location. Mammographically, it presented as a suspicious irregular mass involving the subcutaneous fat pad with skin thickening. High echogenicity constituted the most relevant sonographic finding. To the best of our knowledge, the magnetic resonance (MR) features have not been previously described. High signal intensity was found on both T1- and T2-weighted precontrast MR images. A dynamic contrast-enhanced study revealed a suspicious focal mass with irregular margins and rim enhancement, with a type 3 time-signal intensity curve. Differential diagnosis with carcinoma and fat necrosis and the value of core biopsy are discussed. (orig.)

  11. Cardiac involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    V. De Gennaro Colonna

    2011-06-01

    Full Text Available Rheumatoid arthritis (RA is a systemic disease of unknown etiology characterized by a chronic inflammatory process mainly leading to destruction of synovial membrane of small and major diarthrodial joints. The prevalence of RA within the general adult population is about 1% and female subjects in fertile age result mostly involved. It’s an invalidating disease, associated with changes in life quality and a reduced life expectancy. Moreover, we can observe an increased mortality rate in this population early after the onset of the disease. The mortality excess can be partially due to infective, gastrointestinal, renal or pulmonary complications and malignancy (mainly lung cancer and non- Hodgkin lymphoma. Among extra-articular complications, cardiovascular (CV involvement represents one of the leading causes of morbidity and mortality. Every cardiac structure can be affected by different pathogenic pathways: heart valves, conduction system, myocardium, endocardium, pericardium and coronary arteries. Consequently, different clinical manifestations can be detected, including: pericarditis, myocarditis, myocardial fibrosis, arrhythmias, alterations of conduction system, coronaropathies and ischemic cardiopathy, valvular disease, pulmonary hypertension and heart failure. Considering that early cardiac involvement negatively affects the prognosis, it is mandatory to identify high CV risk RA patients to better define long-term management of this population.

  12. Laryngeal Involvement of Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Ariel B. Grobman

    2012-01-01

    Full Text Available The objectives of this paper are to discuss a rare cause of laryngeal multiple myeloma, to review unique pathologic findings associated with plasma cell neoplasms, to discuss epidemiology, differential diagnosis, and treatment options for plasma cell neoplasms of the larynx. Laryngeal multiple myeloma, also noted in the literature as “metastatic” multiple myeloma, presenting as a de novo laryngeal mass is extremely rare with few reported cases. Laryngeal involvement of extramedullary tumors is reported to be between 6% and 18% with the epiglottis, glottis, false vocal folds, aryepiglottic folds, and subglottis involved in decreasing the order of frequency. We present the case of a 58-year-old male with a history of IgA smoldering myeloma who presented to a tertiary care laryngological practice with a two-month history of dysphonia, which was found to be laryngeal involvement of multiple myeloma. We review the classification of and differentiation between different plasma cell neoplasms, disease workups, pathologic findings, and treatment options.

  13. Constraints on the Higgs Sector from Processes Involving Photons

    OpenAIRE

    Krawczyk,Maria

    1998-01-01

    The Higgs sector of the Standard Model and of the Two Higgs Doublet Extensions of SM, MSSM and the general 2HDM, can be tested in processes involving photons. A short review of the corresponding results is presented.

  14. Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat/cholesterol diet.

    Science.gov (United States)

    Yongming, Pan; Zhaowei, Cai; Yichao, Ma; Keyan, Zhu; Liang, Chen; Fangming, Chen; Xiaoping, Xu; Quanxin, Ma; Minli, Chen

    2015-01-16

    A long-term high-fat/cholesterol (HFC) diet leads to insulin resistance (IR), which is associated with inflammation, atherosclerosis (AS), cardiac sympathovagal imbalance, and cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) and nuclear factor ĸB (NF-κB) are involved in the development of IR-AS. Thus, we elucidated the pathological molecular mechanism of IR-AS by feeding an HFC diet to Tibetan minipigs to induce IR and AS. Male Tibetan minipigs were fed either a normal diet or an HFC diet for 24 weeks. Thereafter, the minipigs were tested for physiological and biochemical blood indices, blood pressure, cardiac function, glucose tolerance, heart rate variability (HRV), and PPAR-associated gene and protein expression levels. HFC-fed minipigs exhibited IR through increased body weight, fasting blood glucose levels, plasma cholesterol and its composition, and insulin and free fatty acid (FFA) levels; decreased insulin sensitivity; impaired glucose tolerance; and hypertension. Increased C-reactive protein (CRP) levels, cardiac dysfunction, depressed HRV, and the up-regulation of PPAR expression in the abdominal aorta concomitant with down-regulation in the heart tissue were observed in HFC-fed minipigs. Furthermore, the levels of NF-κBp65, IL-1β, TNF-α, MCP-1, VCAM-1, ICAM-1, MMP-9, and CRP proteins were also significantly increased. These data suggest that HFC-fed Tibetan minipigs develop IR and AS and that PPARs are involved in cardiovascular remodeling and impaired function.

  15. National Parks and social involvement - an argument

    Directory of Open Access Journals (Sweden)

    J.A. Loader

    1994-09-01

    Full Text Available Discrimination, whether institutionalised or not, is described as the expression of prejudice, which, it is argued, is derived from projectionism, or the supposition that one's own perception coincides with reality and is therefore the only valid one. It is the result of naive ignorance of the world view(s by which human attitudes are shaped. By means of the ecologically congenial concepts of interrelatedness and holism, it is here argued as an alternative that social involvement is (or, should be an intrinsic part of conservation. A possible model for the purpose and some practical considerations are suggested.

  16. DHA involvement in neurotransmission process

    Directory of Open Access Journals (Sweden)

    Vancassel Sylvie

    2007-05-01

    Full Text Available The very high enrichment of the nervous system in the polyunsaturated fatty acids, arachidonic (AA, 20: 4n-6 and docosahexaenoic acids (DHA, 22: 6n-3, is dependant of the dietary availability of their respective precursors, linoleic (18: 2n-6 and_-linolenic acids (18: 3n-3. Inadequate amounts of DHA in brain membranes have been linked to a wide variety of abnormalities ranging from visual acuity and learning irregularities, to psychopathologies. However, the molecular mechanisms involved remain unknown. Several years ago, we hypothesized that a modification of DHA contents of neuronal membranes by dietary modulation could change the neurotransmission function and then underlie inappropriate behavioural response. We showed that, in parallel to a severe loss of brain DHA concomitant to a compensatory substitution by 22:5n-6, the dietary lack of α-linolenic acid during development induced important changes in the release of neurotransmitters (dopamine, serotonin, acetylcholine in cerebral areas specifically involved in learning, memory and reward processes. Data suggested alteration of presynaptic storage process and dysregulations of reciprocal functional interactions between monoaminergic and cholinergic pathways. Moreover, we showed that recovery of these neurochemical changes was possible when the deficient diet was switched to a diet balanced in n-3 and n-6 PUFA before weaning. The next step is to understand the mechanism involved. Particularly, we focus on the study of the metabolic cooperation between the endothelial cell, the astrocyte and the neuron which regulate synaptic transmission.These works could contribute to the understanding of the link between some neuropsychiatric disorders and the metabolism of n-3 PUFA, through their action on neurotransmission.

  17. Neuronal involvement in cisplatin neuropathy

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Helweg-Larsen, Susanne Elisabeth; Schmalbruch, H

    2007-01-01

    Although it is well known that cisplatin causes a sensory neuropathy, the primary site of involvement is not established. The clinical symptoms localized in a stocking-glove distribution may be explained by a length dependent neuronopathy or by a distal axonopathy. To study whether the whole neuron...... of large dorsal root ganglion cells. Motor conduction studies, autonomic function and warm and cold temperature sensation remained unchanged at all doses of cisplatin treatment. The results of these studies are consistent with degeneration of large sensory neurons whereas there was no evidence of distal...

  18. Panic Disorder: Is the PAG Involved?

    Directory of Open Access Journals (Sweden)

    Cristina Marta Del-Ben

    2009-01-01

    Full Text Available Data from studies with humans have suggested that abnormalities of midbrain structures, including the periaqueductal gray matter (PAG, could be involved in the neurobiology of panic disorder (PD. The electrical stimulation of the PAG in neurosurgical patients induces panic-like symptoms and the effect of drugs that are effective in the treatment of PD in the simulation of public speaking model of anxiety is in agreement with data from animal models of PD. Structural neuroimaging studies have shown increases in gray matter volume of midbrain and pons of PD patients. There is also evidence of lower serotonin transporter and receptor binding, and increases of metabolism in the midbrain of PD patients. Nevertheless, these midbrain abnormalities can not be considered as specific findings, since neuroimaging data indicate that PD patients have abnormalities in other brain structures that process fear and anxiety.

  19. Panic disorder: is the PAG involved?

    Science.gov (United States)

    Del-Ben, Cristina Marta; Graeff, Frederico Guilherme

    2009-01-01

    Data from studies with humans have suggested that abnormalities of midbrain structures, including the periaqueductal gray matter (PAG), could be involved in the neurobiology of panic disorder (PD). The electrical stimulation of the PAG in neurosurgical patients induces panic-like symptoms and the effect of drugs that are effective in the treatment of PD in the simulation of public speaking model of anxiety is in agreement with data from animal models of PD. Structural neuroimaging studies have shown increases in gray matter volume of midbrain and pons of PD patients. There is also evidence of lower serotonin transporter and receptor binding, and increases of metabolism in the midbrain of PD patients. Nevertheless, these midbrain abnormalities can not be considered as specific findings, since neuroimaging data indicate that PD patients have abnormalities in other brain structures that process fear and anxiety.

  20. Renal involvement in antiphospholipid syndrome.

    Science.gov (United States)

    Sciascia, Savino; Cuadrado, Maria José; Khamashta, Munther; Roccatello, Dario

    2014-05-01

    Antiphospholipid syndrome (APS) is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for antiphospholipid antibodies (aPLs). APS can be isolated (known as primary APS) or associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE; known as secondary APS). The kidney is a major target organ in APS and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal arteries, glomerular capillaries and renal veins); events reflect the site and size of the involved vessels. Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal prognosis is affected by the presence of aPLs in patients with lupus nephritis and can be poor. In patients with SLE and aPLs, biopsy should be performed because inflammatory and thrombotic lesions require different therapeutic approaches. Renal involvement in patients with definite APS is treated by anticoagulation with long-term warfarin. The range of renal manifestations associated with APS is broadening and, therefore, aPLs have increasing relevance in end-stage renal disease, transplantation and pregnancy.

  1. Subfascial involvement in glomuvenous malformation

    Energy Technology Data Exchange (ETDEWEB)

    Shaikh, Raja; Alomari, Ahmad I.; Chaudry, Gulraiz [Boston Children' s Hospital, Division of Interventional Radiology, Boston, MA (United States); Mulliken, John B. [Boston Children' s Hospital, Division of Plastic Surgery, Boston, MA (United States); Fishman, Steven J. [Boston Children' s Hospital, Department of Surgery, Boston, MA (United States); Kozakewich, Harry P.W. [Boston Children' s Hospital, Department of Pathology, Boston, MA (United States)

    2014-07-15

    Glomuvenous malformation (GVM) is an inherited autosomal dominant trait. The lesions, which appear as bluish nodules or plaque-like cutaneous elevations, are usually tender and more firm than sporadic venous malformations. Conventionally, the lesions are thought to be limited to the cutaneous and subcutaneous tissue planes. The objective was to characterize the depth of involvement of GVM lesions. Magnetic resonance imaging (MRI) findings in GVM were retrospectively evaluated by two radiologists. The signal characteristics, tissue distribution, pattern of contrast enhancement of the lesions in GVM were documented. Thirty patients (19 female) aged 1-35 years (mean 18 years) were diagnosed with GVM based on clinical features (n = 20) and/or histopathological findings (n = 10). The lesions were present in the lower extremity (n = 15), upper extremity (n = 6), cervico-facial region (n = 6), pelvis (n = 2), and chest wall (n = 1). All patients had skin and subcutaneous lesions. Fifty percent of the patients (n = 15) demonstrated subfascial intramuscular (n = 15), intra-osseous (n = 1), and intra-articular involvement (n = 1). Contrary to the conventional belief that GVMs are generally limited to the skin and subcutaneous tissue, deep subfascial extension of the lesions is common. (orig.)

  2. (1) H NMR Spectra. Part 28: Proton chemical shifts and couplings in three-membered rings. A ring current model for cyclopropane and a novel dihedral angle dependence for (3) J(HH) couplings involving the epoxy proton.

    Science.gov (United States)

    Abraham, Raymond J; Leonard, Paul; Tormena, Cláudio F

    2012-04-01

    The (1) H chemical shifts of selected three-membered ring compounds in CDCl(3) solvent were obtained. This allowed the determination of the substituent chemical shifts of the substituents in the three-membered rings and the long-range effect of these rings on the distant protons. The substituent chemical shifts of common substituents in the cyclopropane ring differ considerably from the same substituents in acyclic fragments and in cyclohexane and were modelled in terms of a three-bond (γ)-effect. For long-range protons (more than three bonds removed), the substituent effects of the cyclopropane ring were analysed in terms of the cyclopropane magnetic anisotropy and steric effect. The cyclopropane magnetic anisotropy (ring current) shift was modelled by (a) a single equivalent dipole perpendicular to and at the centre of the cyclopropane ring and (b) by three identical equivalent dipoles perpendicular to the ring placed at each carbon atom. Model (b) gave a more accurate description of the (1) H chemical shifts and was the selected model. After parameterization, the overall root mean square error for the dataset of 289 entries was 0.068 ppm. The anisotropic effects are significant for the cyclopropane protons (ca 1 ppm) but decrease rapidly with distance. The heterocyclic rings of oxirane, thiirane and aziridine do not possess a ring current. (3) J(HH) couplings of the epoxy ring proton with side-chain protons were obtained and shown to be dependent on both the H-C-C-H and H-C-C-O orientations. Both density functional theory calculations and a simple Karplus-type equation gave general agreement with the observed couplings (root mean square error 0.5 Hz over a 10-Hz range).

  3. Cutaneous Plasmacytosis with Perineural Involvement

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Brezinski

    2014-01-01

    Full Text Available Importance. Cutaneous and systemic plasmacytosis are rare conditions of unknown etiology with characteristic red-brown skin lesions and a mature polyclonal plasma cell infiltrate within the dermis. Perineural plasma cell infiltrates may be a histologic clue to the diagnosis of cutaneous plasmacytosis. Observations. Our patient had a five-year history of persistent reddish-brown plaques on the neck and trunk without systemic symptoms. Histologic examination showed dermal perivascular and perineural plasma cells with excess lambda light chain expression. Due to decreased quality of life caused by his skin lesions, he was placed on a chemotherapeutic regimen with bortezomib. Conclusions and Relevance. The patient was diagnosed with cutaneous plasmacytosis based on classic histopathology results with a recently characterized pattern of perineural involvement. Bortezomib therapy was initiated to manage his skin eruption, which has not been previously described as a treatment for this chronic condition.

  4. CHANGE AT CERN - BE INVOLVED

    CERN Multimedia

    2002-01-01

    The encouragement of individual members of staff to contribute to the work of the task forces by making suggestions via the form on the Users'page of the web has been successful. Therefore, as announced by the Director General in his talk to the Staff in April, the management would like staff to continue to be involved in the change process by making further suggestions. Suggestions received will be distributed to the Director(s)/Division Leader(s) concerned, for reply and action where appropriate. The Director General has set up a small Panel that will ensure the proper processing of the ideas and will present a regular overview to the Director General. Members of the Panel are: Jan van der Boon, Vincent Hatton, Karl-Heinz Kissler, Thomas Pettersson, Florian Sonnemann, and Horst Wenninger.

  5. Metronidazole neurotoxicity: Sequential neuroaxis involvement

    Directory of Open Access Journals (Sweden)

    Kyung-Il Park

    2011-01-01

    Full Text Available Neurological manifestation of metronidazole toxicity include neuropathy and encephalopathy. We report a 67-year-old man with progressive painful paresthesias involving all the four limbs of 3 weeks′ duration before admission. He had been treated with metronidazole and cephalosporin for 10 weeks for a hepatic abscess. Five weeks after the symptom onset, he complained of dysarthria and limb ataxia. Magnetic resonance imaging revealed signal abnormalities in the splenium of the corpus callosum and bilateral dentate nuclei. A few hours after brain imaging, the patient exhibited excessive diaphoresis and fluctuation in blood pressure, which resolved within several hours after discontinuation of metronidazole. Whereas his speech returned to near normal within approximately 1 week, a burning sensation was not completely relieved, even 6 months after discharge.

  6. Measuring Purchase‐decision involvement ,

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2014-08-01

    Full Text Available Nowadays, increasing competition is forcing businesses to pay more attention on customer satisfaction providing strong customer services. Increased competition has also increased marketing activities. This paper presents an empirical investigation to determine important factors influencing purchase decision involvement in food industry in city of Tehran, Iran. The study designs a questionnaire in Likert scale, distributes it among 270 experts in food industry and, using principle component (PCA analysis, extracts important group of factors. The questionnaire consists of 27 questions, which is reduced to 23 questions because of sensitivity of the PCA to Skewness of data. Cronbach alpha is calculated as 0.81, which is well above the minimum acceptable level. The results indicate that there were four factors including individual differences, product validation, triggers and dependent behavior influencing purchasing decisions.

  7. Kidney involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    P. Lazzarini

    2011-09-01

    Full Text Available Rheumatoid Arthritis (RA is a widespread disease and its renal involvement, relatively common, is clinically significant because worsens course and mortality of the primary disease. There is still no agreement on the prevalence of renal disorders in RA: data analysis originates from different sources, as death certificates, autopsies, clinical and laboratory findings and kidney biopsies, each with its limitations. Histoimmunological studies on bioptical specimens of patients with RA and kidney damage, led to clarify prevalent pathologies. In order of frequency: glomerulonephritis and amyloidosis (60-65% and 20-30% respectively, followed by acute or chronic interstitial nephritis. Kidney injury during RA includes secondary renal amyloidosis, nephrotoxic effects of antirheumatic drugs and nephropathies as extra-articular manifestations (rheumatoid nephropathy. Amyloidosis affects survival, increases morbidity and is the main cause of end stage renal disease in patients with RA and nephropathy. Strong association between RA activity and amyloidosis needs the use of immunosuppressive and combined therapies, to prevent this complication and reduce risk of dialysis. Long-lasting and combined RA pharmacotherapy involves various renal side effects. In this review we describe NSAIDs and DMARDs (Disease-Modifying Antirheumatic Drugs nephrotoxicity, particularly by gold compounds, D-penicillamine, cyclosporine A and methotrexate. Rare cases of IgA glomerulonephritis during immunomodulating therapy with leflunomide and TNF blocking receptor (etanercept are reported; real clinical significance of this drug-related nephropathy will be established by development of RA treatment. In RA nephropathies, mesangial glomerulonephritis is the most frequent histological lesion (35-60 % out of biopsies from patients with urinary abnormalities and/or kidney impairment, followed by minimal change glomerulopathy (3-14% and p-ANCA positive necrotizing crescentic

  8. Involving human forecasters in numerical prediction systems

    Directory of Open Access Journals (Sweden)

    V. Homar

    2006-01-01

    Full Text Available Human forecasters routinely improve upon the output from numerical weather prediction models and often have keen insight to model biases and shortcomings. This wealth of knowledge about model performance is largely untapped, however, as it is used only at the end point in the forecast process to interpret the model-predicted fields. Yet there is no reason why human forecasters cannot intervene at other earlier times in the numerical weather prediction process, especially when an ensemble forecasting system is in use. Human intervention in ensemble creation may be particularly helpful for rare events, such as severe weather events, that are not predicted well by numerical models. The USA/NOAA SPC/NSSL Spring Program 2003 tested an ensemble generation method in which human forecasters were involved in the ensemble creation process. The forecaster highlighted structures of interest and, using an adjoint model, a set of perturbations were obtained and used to generate a 32-member ensemble. The results show that this experimental ensemble improves upon the operational numerical forecasts of severe weather. The human-generated ensemble is able to provide improved guidance on high-impact weather events, but lacks global dispersion and produces unreliable forecasts for non-hazardous weather events. Further results from an ensemble constructed by combining the operational ensemble perturbations with the human-generated perturbations shows promising skill for the forecast of severe weather while avoiding the problem of limited global dispersion. The value of human beings in the creation of ensembles designed to target specific high- impact weather events is potentially large. Further investigation of the value of forecasters being part of the ensemble creation process is strongly recommended. There remains a lot to learn about how to create ensembles for short-range forecasts of severe weather, and we need to make better use of the skill and experience of

  9. Evidence for a model of agonist-induced activation of 5-hydroxytryptamine 2A serotonin receptors that involves the disruption of a strong ionic interaction between helices 3 and 6.

    Science.gov (United States)

    Shapiro, David A; Kristiansen, Kurt; Weiner, David M; Kroeze, Wesley K; Roth, Bryan L

    2002-03-29

    5-Hydroxytryptamine 2A (5-HT2A) receptors are essential for the actions of serotonin (5-hydroxytryptamine (5-HT)) on physiological processes as diverse as vascular smooth muscle contraction, platelet aggregation, perception, and emotion. In this study, we investigated the molecular mechanism(s) by which 5-HT activates 5-HT2A receptors using a combination of approaches including site-directed mutagenesis, molecular modeling, and pharmacological analysis using the sensitive, cell-based functional assay R-SAT. Alanine-scanning mutagenesis of residues close to the intracellular end of H6 of the 5-HT2A receptor implicated glutamate Glu-318(6.30) in receptor activation, as also predicted by a newly constructed molecular model of the 5-HT2A receptor, which was based on the x-ray structure of bovine rhodopsin. Close examination of the molecular model suggested that Glu-318(6.30) could form a strong ionic interaction with Arg-173(3.50) of the highly conserved "(D/E)RY motif" located at the interface between the third transmembrane segment and the second intracellular loop (i2). A direct prediction of this hypothesis, that disrupting this ionic interaction by an E318(6.30)R mutation would lead to a highly constitutively active receptor with enhanced affinity for agonist, was confirmed using R-SAT. Taken together, these results predict that the disruption of a strong ionic interaction between transmembrane helices 3 and 6 of 5-HT2A receptors is essential for agonist-induced receptor activation and, as recently predicted by ourselves (B. L. Roth and D. A. Shapiro (2001) Expert Opin. Ther. Targets 5, 685-695) and others, that this may represent a general mechanism of activation for many, but not all, G-protein-coupled receptors.

  10. Modeling VLE and GLE of Systems Involving Polymers by Using SRK Equation of State%SRK状态方程用于聚合物体系的汽液和气液平衡

    Institute of Scientific and Technical Information of China (English)

    计伟荣

    2007-01-01

    A simple extension of cubic equations of state (EOS) to polymer systems has been proposed.The Soave-Redlich-Kwong (SRK) EOS was taken as a prototype to be used to describe the PVT behavior of polymer melts in a wide temperature and pressure range.Combined with a modified Huron-Vidal 8E-mixing rule it was applied for modeling vapor-liquid equilibria of polymer-solvent solutions and the solubility of supercritical gases in polymer melts.Satisfactory results are obtained.

  11. Lyman α photolysis of solid nitromethane (CH3NO2) and D3-nitromethane (CD3NO2)--untangling the reaction mechanisms involved in the decomposition of model energetic materials.

    Science.gov (United States)

    Maksyutenko, Pavlo; Muzangwa, Lloyd G; Jones, Brant M; Kaiser, Ralf I

    2015-03-21

    Solid nitromethane (CH3NO2) along with its isotopically labelled counterpart D3-nitromethane (CD3NO2) ices were exposed to Lyman α photons to investigate the mechanism involved in the decomposition of energetic materials in the condensed phase. The chemical processes in the ices were monitored online and in situ via infrared spectroscopy complimented by temperature programmed desorption studies utilizing highly sensitive reflectron time-of-flight mass spectrometry coupled with pulsed photoionization (ReTOF-PI) at 10.49 eV. The infrared data revealed the formation of cis-methylnitrite (CH3ONO), formaldehyde (H2CO), water (H2O), carbon monoxide (CO), and carbon dioxide (CO2). Upon sublimation of the irradiated samples, three classes of higher molecular weight products, which are uniquely formed in the condensed phase, were identified via ReTOF-PI: (i) nitroso compounds [nitrosomethane (CH3NO), nitrosoethane (C2H5NO), nitrosopropane (C3H7NO)], (ii) nitrite compounds [methylnitrite (CH3ONO), ethylnitrite (C2H5ONO), propylnitrite (C3H7ONO)], and (iii) higher molecular weight molecules [CH3NONOCH3, CH3NONO2CH3, CH3OCH2NO2, ONCH2CH2NO2]. The mechanistical information obtained in the present study suggest that the decomposition of nitromethane in the condensed phase is more complex compared to the gas phase under collision-free conditions opening up not only hitherto unobserved decomposition pathways of nitromethane (hydrogen atom loss, oxygen atom loss, retro carbene insertion), but also the blocking of several initial decomposition steps due to the 'matrix cage effect'.

  12. 缺失数据下含几何分布的对数线性模型的EM算法%The EM Algorithm in Logistic Linear Models with Geometric Distribution Involving Missing Data

    Institute of Scientific and Technical Information of China (English)

    王继霞; 刘次华

    2009-01-01

    In this paper,a geometric response and normal covariace model for the missing data are assumed.We fit the model using the Monte Carlo EM(Expectation and Maximization) algorithm.The E-step is derived by Metropolis-Hastings algorithm to generate a sample for missing data,and the M-Step is done by Newton-Raphson to maximize the likelihood function.Asymptotic variances and the standard errors of the MLE of parameters are derived using the observed Fisher information.%本文研究缺失数据下对数线性模型参数的极大似然估计问题.通过Monte-Carlo EM算法去拟合所提出的模型.其中,在期望步中利用Metropolis-Hastings算法产生一个缺失数据的样本,在最大化步中利用Newton-Raphson迭代使似然函数最大化.最后,利用观测数据的Fisher信息得到参数极大似然估计的渐近方差和标准误差.

  13. Role of Electrostatic Interactions in Binding of Peptides and Intrinsically Disordered Proteins to Their Folded Targets: 2. The Model of Encounter Complex Involving the Double Mutant of the c-Crk N-SH3 Domain and Peptide Sos.

    Science.gov (United States)

    Yuwen, Tairan; Xue, Yi; Skrynnikov, Nikolai R

    2016-03-29

    In the first part of this work (paper 1, Xue, Y. et al. Biochemistry 2014 , 53 , 6473 ), we have studied the complex between the 10-residue peptide Sos and N-terminal SH3 domain from adaptor protein c-Crk. In the second part (this paper), we designed the double mutant of the c-Crk N-SH3 domain, W169F/Y186L, with the intention to eliminate the interactions responsible for tight peptide-protein binding, while retaining the interactions that create the initial electrostatic encounter complex. The resulting system was characterized experimentally by measuring the backbone and side-chain (15)N relaxation rates, as well as binding shifts and (1)H(N) temperature coefficients. In addition, it was also modeled via a series of ∼5 μs molecular dynamics (MD) simulations recorded in a large water box under an Amber ff99SB*-ILDN force field. Similar to paper 1, we have found that the strength of arginine-aspartate and arginine-glutamate salt bridges is overestimated in the original force field. To address this problem we have applied the empirical force-field correction described in paper 1. Specifically, the Lennard-Jones equilibrium distance for the nitrogen-oxygen pair across Arg-to-Asp/Glu salt bridges has been increased by 3%. This modification led to MD models in good agreement with the experimental data. The emerging picture is that of a fuzzy complex, where the peptide "dances" over the surface of the protein, making transient contacts via salt-bridge interactions. Every once in a while the peptide assumes a certain more stable binding pose, assisted by a number of adventitious polar and nonpolar contacts. On the other hand, occasionally Sos flies off the protein surface; it is then guided by electrostatic steering to quickly reconnect with the protein. The dynamic interaction between Sos and the double mutant of c-Crk N-SH3 gives rise to only small binding shifts. The peptide retains a high degree of conformational mobility, although it is appreciably slowed down due

  14. 信号交叉口右转机动车与行人冲突运动模型%A Conflict Model Involving Right-turning Vehicles and Cross-walking Pedestrians at Signalized Intersections

    Institute of Scientific and Technical Information of China (English)

    鲍怡婷; 周竹萍; 徐永能

    2016-01-01

    Normally,the right-turning movement of vehicles at signalized intersections is not controlled.Thus, there are potential risks of conflicts between the right-turning vehicles and cross-walking pedestrians.Current studies ad-dressed on the identification and classification of such conflicts,no theoretical model is proposed to analyze such processes of conflicts.With the purpose to reduce conflicts and improve safety of pedestrians,a new simulation model to describe the conflict processes between right-turning vehicles and cross-walking pedestrians is proposed in this study.The decision-making process of right-turning vehicles is studied.Then the mechanism of conflicts between vehicles and pedestrians is analyzed.Finally,a vehicle-pedestrian conflict model is established.Meanwhile,the coefficients for this model are calibra-ted using actual data including vehicle speed and gap acceptance.A simulation study is then conducted to optimize the measurements for safety evaluation:time-to-collision (TTC),post-encroachment time (PET),safety braking decelera-tion,and gap time.The results reveal that PET is the most significant measurement to evaluate vehicle-pedestrian con-flict.The accuracy analysis results show that the deviation of vehicle speed and PET between simulation and actual data is less than 5%,which indicates the validity of this model.An implementation of sensitivity analysis shows that PET of small size intersections increases 10% compared with large size of intersections,which indicates that small intersections have the advantage to reduce the severity of conflicts.%在一些信号交叉口,右转机动车的转弯行为不受信号控制,容易与过街行人发生冲突。现有冲突研究的内容多为冲突判别和冲突分级研究,对人车冲突运动过程研究相对较少。为减少交通冲突,提高行人过街安全性,提出一种新的右转机动车与行人冲突运动过程的仿真模型。研究右转车辆的决策过程,

  15. Quantitative T2 combined with texture analysis of nuclear magnetic resonance images identify different degrees of muscle involvement in three mouse models of muscle dystrophy: mdx, Largemyd and mdx/Largemyd.

    Directory of Open Access Journals (Sweden)

    Aurea B Martins-Bach

    Full Text Available Quantitative nuclear magnetic resonance imaging (MRI has been considered a promising non-invasive tool for monitoring therapeutic essays in small size mouse models of muscular dystrophies. Here, we combined MRI (anatomical images and transverse relaxation time constant-T2-measurements to texture analyses in the study of four mouse strains covering a wide range of dystrophic phenotypes. Two still unexplored mouse models of muscular dystrophies were analyzed: The severely affected Largemyd mouse and the recently generated and worst double mutant mdx/Largemyd mouse, as compared to the mildly affected mdx and normal mice. The results were compared to histopathological findings. MRI showed increased intermuscular fat and higher muscle T2 in the three dystrophic mouse models when compared to the wild-type mice (T2: mdx/Largemyd: 37.6±2.8 ms; mdx: 35.2±4.5 ms; Largemyd: 36.6±4.0 ms; wild-type: 29.1±1.8 ms, p<0.05, in addition to higher muscle T2 in the mdx/Largemyd mice when compared to mdx (p<0.05. The areas with increased muscle T2 in the MRI correlated spatially with the identified histopathological alterations such as necrosis, inflammation, degeneration and regeneration foci. Nevertheless, muscle T2 values were not correlated with the severity of the phenotype in the 3 dystrophic mouse strains, since the severely affected Largemyd showed similar values than both the mild mdx and worst mdx/Largemyd lineages. On the other hand, all studied mouse strains could be unambiguously identified with texture analysis, which reflected the observed differences in the distribution of signals in muscle MRI. Thus, combined T2 intensity maps and texture analysis is a powerful approach for the characterization and differentiation of dystrophic muscles with diverse genotypes and phenotypes. These new findings provide important noninvasive tools in the evaluation of the efficacy of new therapies, and most importantly, can be directly applied in human

  16. Bcl-2, Bcl-xL, and p-AKT are involved in neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma

    Science.gov (United States)

    Phatak, Nitasha R.; Stankowska, Dorota L.

    2016-01-01

    Purpose Brn3b is a class IV POU domain transcription factor that plays an important role in the development of retinal ganglion cells (RGCs), RGC survival, and particularly axon growth and pathfinding. Our previous study demonstrated that recombinant adenoassociated virus serotype 2 (rAAV-2)–mediated overexpression of Brn3b in RGCs promoted neuroprotection in a rodent model of glaucoma. However, the mechanisms underlying neuroprotection of RGCs in rats overexpressing Brn3b in animal models of glaucoma remain largely unknown. The goal of this study was to understand some of the mechanisms underlying the neuroprotection of RGCs overexpressing Brn3b during intraocular pressure (IOP) elevation in Brown Norway rats. Methods One eye of Brown Norway rats (Rattus norvegicus) was injected with an AAV construct encoding either green fluorescent protein (GFP; recombinant adenoassociated virus–green fluorescent protein, rAAV-hSyn-GFP) or Brn3b (rAAV-hSyn-Brn3b). Expression of antiapoptotic proteins, including B cell lymphoma/leukemia-2 (Bcl-2) family proteins (Bcl-2 and Bcl-xL), and p-AKT, was observed following immunostaining of rat retinas that overexpress Brn3b. In a different set of experiments, intraocular pressure was elevated in one eye of Brown Norway rats, which was followed by intravitreal injection with AAV constructs encoding either GFP (rAAV-CMV-GFP) or Brn3b (rAAV-CMV-Brn3b). Retinal sections were stained for prosurvival factors, including Bcl-2, Bcl-XL, and p-AKT. Results AAV-mediated expression of transcription factor Brn3b promoted statistically significant upregulation of the Bcl-2 protein and increased expression of p-AKT in RGCs of Brown Norway rats. In addition, following IOP elevation, AAV-mediated Brn3b expression also statistically significantly increased levels of Bcl-2 in the RGC layer in Brown Norway rats. Conclusions Adenoassociated virus–mediated Brn3b protein overexpression may promote neuroprotection by upregulating key antiapoptotic

  17. Quantitative T2 Combined with Texture Analysis of Nuclear Magnetic Resonance Images Identify Different Degrees of Muscle Involvement in Three Mouse Models of Muscle Dystrophy: mdx, Largemyd and mdx/Largemyd

    Science.gov (United States)

    Martins-Bach, Aurea B.; Malheiros, Jackeline; Matot, Béatrice; Martins, Poliana C. M.; Almeida, Camila F.; Caldeira, Waldir; Ribeiro, Alberto F.; Loureiro de Sousa, Paulo; Azzabou, Noura; Tannús, Alberto; Carlier, Pierre G.; Vainzof, Mariz

    2015-01-01

    Quantitative nuclear magnetic resonance imaging (MRI) has been considered a promising non-invasive tool for monitoring therapeutic essays in small size mouse models of muscular dystrophies. Here, we combined MRI (anatomical images and transverse relaxation time constant—T2—measurements) to texture analyses in the study of four mouse strains covering a wide range of dystrophic phenotypes. Two still unexplored mouse models of muscular dystrophies were analyzed: The severely affected Largemyd mouse and the recently generated and worst double mutant mdx/Largemyd mouse, as compared to the mildly affected mdx and normal mice. The results were compared to histopathological findings. MRI showed increased intermuscular fat and higher muscle T2 in the three dystrophic mouse models when compared to the wild-type mice (T2: mdx/Largemyd: 37.6±2.8 ms; mdx: 35.2±4.5 ms; Largemyd: 36.6±4.0 ms; wild-type: 29.1±1.8 ms, p<0.05), in addition to higher muscle T2 in the mdx/Largemyd mice when compared to mdx (p<0.05). The areas with increased muscle T2 in the MRI correlated spatially with the identified histopathological alterations such as necrosis, inflammation, degeneration and regeneration foci. Nevertheless, muscle T2 values were not correlated with the severity of the phenotype in the 3 dystrophic mouse strains, since the severely affected Largemyd showed similar values than both the mild mdx and worst mdx/Largemyd lineages. On the other hand, all studied mouse strains could be unambiguously identified with texture analysis, which reflected the observed differences in the distribution of signals in muscle MRI. Thus, combined T2 intensity maps and texture analysis is a powerful approach for the characterization and differentiation of dystrophic muscles with diverse genotypes and phenotypes. These new findings provide important noninvasive tools in the evaluation of the efficacy of new therapies, and most importantly, can be directly applied in human translational research

  18. Lymphoblastic lymphoma involving multiple vertebrae.

    Science.gov (United States)

    Li, Da; Xu, Yu-Lun; Wu, Zhen

    2017-09-26

    Acute lymphoblastic lymphoma (ALL) was a malignant hematological disease in childhood but rarely, initially involved epidural compartment in adult. A 20-year-old male presented with progressive osphyalgia for 2 months and left lower motor weakness for 2 weeks with constipation. Physical examination revealed decreased muscle strength and numbness of left lower limb, and abnormal gait. Contrasted MRI showed multiple vertebrae of hypointense T1 signals (C2/C4/C7/T5/T8/T9/T12/L2/L4) and an intraspinal epidural lesion (L2-4). Subtotal resection was achieved. Histopathology suggested malignant B-cell lymphoma with Ki-67 of 90% and positivity of leukocyte common antigen (LCA). A bone marrow biopsy was unequivocally diagnostic of B-cell ALL followed by chemotherapy (Methotrexate) and partial recovery was observed. The present case was the oldest patient with epidural ALL. The radiographic changes in multiple vertebrae suggested metabolic, hematological, or granulomatous disease. The marrow biopsy was necessary if without hypercalcemia and abnormal peripheral blood examination. Accurate pathological diagnosis was essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. PULMONARY INVOLVEMENT IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    D. V. Bestaev

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA is an autoimmune disease with erosive and destructive polyarthritis and systemic manifestations. Pulmonary involvement (PI is common in RA. With high-resolution computed tomography, the detection rate of PI in RA is as high as 50%. PI is a direct cause of death in 10–20% of patients with RA. Autoimmune mechanisms play a leading part in the development of PI in RA. Under the hypothesis advanced by M. Selman et al., that impaired alveolocyte regeneration processes after injury rather inflammation underlie the pathogenesis of pulmonary fibrosis. The pathological process is triggered by damaged alveolocytes and characterized by the migration and proliferation of fibroblasts and myofibroblasts, the suppressed apoptosis of the latter, and the enhanced activity of pneumofibrosis-stimulating cytokines. This gives rise to remodeling of the extracellular matrix, including destruction of the basement membrane, angiogenesis, and fibrosis. The paper considers the types of lung injury in RA and main methods for diagnosis and therapy.

  20. Ego, Alter and Object: explaining Personal Involvement with a Social Object Based on Perceived Collective Involvement and Group Identification

    Directory of Open Access Journals (Sweden)

    Joao Wachelke

    2016-01-01

    Full Text Available The present paper aims at testing a model to predict personal involvement with a social object which was inspired by the social psychological triangle proposed by Moscovici. The triangle bridges three essential aspects of social psychology: the individual, the Other and a social object. It was operationalized as an empirical model to explain personal involvement with a social topic from two predictors: perceived collective involvement of group members with the same topic and group identification. The sample was formed by 805 Brazilian undergraduates. The participants completed scales that measured their identification with university students, their perception of students' involvement with two social objects, university course or job, and their own personal involvement with those topics. Regression analyses supported the hypothesis that group identification, perceived collective involvement and their interaction maintained positive relations with personal involvement. Discussion focuses on the relativity of results to specific objects, the complexity of determinant factors of personal involvement and the pertinence of the triangular look to characterize social psychological research.

  1. Evaluating Parent Involvement. Issue Paper No. 1.

    Science.gov (United States)

    Safran, Daniel

    This paper poses a series of questions to assist programs in deciding what it is about parent involvement that they wish to evaluate. The questions focus on the nature of parent involvement, why parent involvement is needed, and what evaluation of parent involvement should include. A conceptual framework for research on the impact of parent…

  2. Defining Parental Involvement: Perception of School Administrators

    Science.gov (United States)

    Young, Clara Y.; Austin, Sheila M.; Growe, Roslin

    2013-01-01

    There remains a plaguing question of how to get parents involved with their child's education. Many parents and educators have different perceptions of what parental involvement means. Miscommunication between the two groups often exists because of how parental involvement is conceptualized. While educators define parental involvement as…

  3. Spatiotemporal chaos involving wave instability

    Science.gov (United States)

    Berenstein, Igal; Carballido-Landeira, Jorge

    2017-01-01

    In this paper, we investigate pattern formation in a model of a reaction confined in a microemulsion, in a regime where both Turing and wave instability occur. In one-dimensional systems, the pattern corresponds to spatiotemporal intermittency where the behavior of the systems alternates in both time and space between stationary Turing patterns and traveling waves. In two-dimensional systems, the behavior initially may correspond to Turing patterns, which then turn into wave patterns. The resulting pattern also corresponds to a chaotic state, where the system alternates in both space and time between standing wave patterns and traveling waves, and the local dynamics may show vanishing amplitude of the variables.

  4. Pilot programs increase men's involvement.

    Science.gov (United States)

    Finger, W R

    1992-08-01

    The UN Population Fund contends that it is the need for family planning (FP) information and services instead of lack of interest that prevents men from participating more in FP. 3 pilot projects in Pakistan, Zimbabwe, and Colombia have acted on this belief. In geographically isolated Mardan, Pakistan, the all male Urban Community Developing Council (UCDC) started a community education project to involve men in FP. 5 UCDC member form 1 community educator team of which there are 60. The teams visit families in Mardan. In 1988, 1 team reported that some men in the households wanted a women to inform their wives about FP. Eventually UCDC located enough women free to be members on 40 teams. In 4 years, contraceptive prevalence among married couples rose from 9% to 21%. Initially the methods tended to be temporary methods but are now longer lasting methods (IUDs, sterilization, injectables, and even a few vasectomies). Other community groups donate about US$541/month to the project. In 1988, the Zimbabwean National Family Planning Council (ZNFPC) began its national education/male motivation project which included sending messages via popular radio soap opera, discussions, and leaflet distribution. The program reached many rural men since they tend to have radios. In 1 year, more men were taking part in decisions about FP (25-35%). ZNFPC has learned it needs to design 2 campaigns to promote condom use: 1 for single and 1 for married men. PROFAMILIA in Colombia began its 1st male clinic in 1985 in Bogota. By 1992, it had 8 male clinics. The key to its success is attractive clinics, low cost vasectomy, individualized care, wide range of services such as condom distribution and treatment of sexually transmitted diseases, and Saturday hours. Despite the 3 projects' successes, they face many obstacles that need to be addressed.

  5. Cardiovascular involvement in psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    V. De Gennaro Colonna

    2011-11-01

    Full Text Available Psoriasis is a chronic, genetically determined and immunomediated inflammatory skin disease that affects 2-3% of the Caucasian population. A considerable proportion of these patients develop a form of inflammatory arthritis known as psoriatic arthritis (PsA, although the prevalence of this has not been well defined. Patients with PsA have a higher mortality rate than the general population and the risk of mortality is related to disease severity at the time of presentation. Endothelial dysfunction and early atherosclerosis have been found in patients with PsA without any cardiovascular disease (CVD risk factors, and experts believe that CVD is one of the leading causes of death, as it is in patients with rheumatoid arthritis (RA. Various disease-related mechanisms may be involved in the development of premature vascular damage in both cases, including an increased synthesis of proinflammatory mediators (such as cytokines, chemokines and adhesion molecules, autoantibodies against endothelial cell components, perturbations in T-cell subsets, genetic polymorphisms, hyperhomocysteinemia, oxidative stress, abnormal vascular repair, and iatrogenic factors. In a recent study of 22 patients with PsA without any signs of CVD, we found that the plasma concentration of asymmetric dimethylarginine (ADMA levels were significantly high and coronary flow reserve (CFR was significantly reduced. Moreover, there was a significant correlation between CFR and plasma ADMA levels in the PsA group. The significant correlation between the reduced CRF and increased ADMA levels suggests that, like patients with early RA, PsA patients suffer from endothelial dysfunction and impaired coronary microcirculation. Active PsA is a risk factor for CVD, and so PsA patients should be screened for subclinical forms of the disease and its risk factors, and an early treatment approach should be adopted.

  6. Cardiac involvement in myotonic dystrophy

    Directory of Open Access Journals (Sweden)

    Koroush Khalighi

    2015-02-01

    Full Text Available Background: Myotonic dystrophy (DM is an inherited progressive muscle disorder caused by defects in muscle proteins. As the incidence of this condition is low, not many are familiar with the multisystem involvement. At times, cardiac disease may even be the predominant manifestation in the form of arrhythmias, conduction defects, and cardiomyopathies. The progression of the disease can lead to sudden, unpredictable death. Thus, it is important to identify this subgroup and treat accordingly. Objective: To identify patients with DM and assess their risk for sudden cardiac death. Methods: Nine patients previously diagnosed with muscular dystrophy were evaluated by cardiologists for various reasons, from a general follow-up to cardiac arrest. All of them had electrocardiograms (EKG and 2-D echocardiograms, and seven of them had further electrophysiological (EP studies. Results: Of the nine patients with DM, eight had EKG evidence of conduction abnormalities ranging from first-degree heart block to complete heart block. Of the seven who had EP studies, five had inducible ventricular tachycardia requiring immediate cardioversion and implantable cardioverter defibrillator (ICD implant. Two of them underwent permanent pacemaker placement due to complete heart block and infra-Hissian block. The remaining two patients opted for a conservative approach with yearly EKG monitoring. Conclusion: Because one-third of the cardiac deaths in patients with DM are sudden, there is a strong need to identify these patients and intervene in those at high risk. Prophylactic pacemaker placement is recommended even in those with minimal conduction system abnormality. However, the common practice is to identify patients at high risk of conduction abnormalities by EP studies and then provide them with prophylactic invasive strategies.

  7. Innovative Pedagogical Processes Involving Educational Technology

    DEFF Research Database (Denmark)

    Weitze, Charlotte Lærke

    it experimented with gamified learning designs. This involved the students designing digital games while implementing learning goals from their curriculum. The project thus created knowledge about which learning designs and competence development models were possible in this environment, which learning designs......This design-based research project investigates the elements, methods, processes and practices that can contribute to the creation of reflected, innovative and motivating learning designs for teachers and students in a hybrid synchronous video-mediated teaching context, with a focus on how...... to create motivating learning for the students. This was done by examining the three actors in the educational institution (students, teachers and the surrounding organisation) individually and relationally. The design-based research project developed knowledge in co-design processes with the three actors...

  8. Yeast ABC proteins involved in multidrug resistance.

    Science.gov (United States)

    Piecuch, Agata; Obłąk, Ewa

    2014-03-01

    Pleiotropic drug resistance is a complex phenomenon that involves many proteins that together create a network. One of the common mechanisms of multidrug resistance in eukaryotic cells is the active efflux of a broad range of xenobiotics through ATP-binding cassette (ABC) transporters. Saccharomyces cerevisiae is often used as a model to study such activity because of the functional and structural similarities of its ABC transporters to mammalian ones. Numerous ABC transporters are found in humans and some are associated with the resistance of tumors to chemotherapeutics. Efflux pump modulators that change the activity of ABC proteins are the most promising candidate drugs to overcome such resistance. These modulators can be chemically synthesized or isolated from natural sources (e.g., plant alkaloids) and might also be used in the treatment of fungal infections. There are several generations of synthetic modulators that differ in specificity, toxicity and effectiveness, and are often used for other clinical effects.

  9. Magnetoreception through Cryptochrome may involve superoxide

    DEFF Research Database (Denmark)

    Solov'yov, Ilia; Schulten, Klaus

    2009-01-01

    is still not understood. One theory for magnetoreception in birds invokes the so-called radical-pair model. This mechanism involves a pair of reactive radicals, whose chemical fate can be influenced by the orientation with respect to the magnetic field of the Earth through Zeeman and hyperfine interactions....... The fact that the geomagnetic field is weak, i.e., ~0.5 G, puts a severe constraint on the radical pair that can establish the magnetic compass sense. For a noticeable change of the reaction yield in a redirected geomagnetic field, the hyperfine interaction has to be as weak as the Earth field Zeeman...... interaction, i.e., unusually weak for an organic compound. Such weak hyperfine interaction can be achieved if one of the radicals is completely devoid of this interaction as realized in a radical pair containing an oxygen molecule as one of the radicals. Accordingly, we investigate here a possible radical...

  10. FIBROBLAST INVOLVEMENT IN SOFT CONNECTIVE TISSUE CALCIFICATION

    Directory of Open Access Journals (Sweden)

    Ivonne eRonchetti

    2013-03-01

    Full Text Available Soft connective tissue calcification is not a passive process, but the consequence of metabolic changes of local mesenchymal cells that, depending on both genetic and environmental factors, alter the balance between pro- and anti-calcifying pathways. While the role of smooth muscle cells and pericytes in ectopic calcifications has been widely investigated, the involvement of fibroblasts is still elusive. Fibroblasts isolated from the dermis of PXE patients and of patients exhibiting PXE-like clinical and histopathological findings offer an attractive model to investigate the mechanisms leading to the precipitation of mineral deposits within elastic fibres and to explore the influence of the genetic background and of the extracellular environment on fibroblast-associated calcifications, thus improving the knowledge on the role of mesenchymal cells on pathologic mineralization.

  11. Scaling Consumers' Purchase Involvement: A New Approach

    Directory of Open Access Journals (Sweden)

    Jörg Kraigher-Krainer

    2012-06-01

    Full Text Available A two-dimensional scale, called ECID Scale, is presented in this paper. The scale is based on a comprehensive model and captures the two antecedent factors of purchase-related involvement, namely whether motivation is intrinsic or extrinsic and whether risk is perceived as low or high. The procedure of scale development and item selection is described. The scale turns out to perform well in terms of validity, reliability, and objectivity despite the use of a small set of items – four each – allowing for simultaneous measurements of up to ten purchases per respondent. The procedure of administering the scale is described so that it can now easily be applied by both, scholars and practitioners. Finally, managerial implications of data received from its application which provide insights into possible strategic marketing conclusions are discussed.

  12. Computational Hemodynamics Involving Artificial Devices

    Science.gov (United States)

    Kwak, Dochan; Kiris, Cetin; Feiereisen, William (Technical Monitor)

    2001-01-01

    This paper reports the progress being made towards developing complete blood flow simulation capability in human, especially, in the presence of artificial devices such as valves and ventricular assist devices. Devices modeling poses unique challenges different from computing the blood flow in natural hearts and arteries. There are many elements needed such as flow solvers, geometry modeling including flexible walls, moving boundary procedures and physiological characterization of blood. As a first step, computational technology developed for aerospace applications was extended in the recent past to the analysis and development of mechanical devices. The blood flow in these devices is practically incompressible and Newtonian, and thus various incompressible Navier-Stokes solution procedures can be selected depending on the choice of formulations, variables and numerical schemes. Two primitive variable formulations used are discussed as well as the overset grid approach to handle complex moving geometry. This procedure has been applied to several artificial devices. Among these, recent progress made in developing DeBakey axial flow blood pump will be presented from computational point of view. Computational and clinical issues will be discussed in detail as well as additional work needed.

  13. What gets dad involved? A longitudinal study of change in parental child caregiving involvement.

    Science.gov (United States)

    Wood, Jeffrey J; Repetti, Rena L

    2004-03-01

    Predictors of change in fathers' and mothers' perceptions of child caregiving involvement were examined. Middle-class 2-parent families (131 mothers and 98 fathers) with a target school-age child participated. Fathers and mothers completed annual questionnaires for 3 consecutive years. Latent growth curve modeling suggested that fathers were likely to increase their relative contribution to child caregiving over the course of 3 years when they had a greater proportion of male children in the family and when life events-particularly changes in employment and financial status-were experienced by the family. Although mothers were responsible for more of the caregiving, their relative level of involvement tended to decrease when there were no young children in the family. Two-parent families may adapt to varying family contexts and life circumstances by shifting caregiving roles and responsibilities over the course of years.

  14. Oxovanadium(IV complexes of bioinorganic and medicinal relevance: Synthesis, characterization and 3D molecular modeling of some oxovanadium(IV complexes involving O, N-donor environment of salicylaldehyde-based sulfa drug Schiff bases

    Directory of Open Access Journals (Sweden)

    R.C. Maurya

    2016-11-01

    Full Text Available The present paper reports the synthesis and characterization of some new sulfa drug based Schiff base oxovanadium(IV complexes of composition, [VO(sal-sdz2(H2O]·H2O, [VO(sal-sgn2(H2O]·H2O, [VO(sal-snm(H2O]·H2O, [VO(sal-smr2(H2O]·H2O and [VO(dadps(H2O]2·2H2O, where sal-sdzH = N-(salicylidenesulfadizine, sal-sgnH = N-(salicylidenesulfaguanidine, sal-snmH = N-(salicylidenesulfanilamide, sal-smrH = N-(salicylidenesulfamerizine, sal-dadpsH2 = N,N′-bis(salicylidene-4,4′-diaminodiphenylsulfone, respectively. Complexes, (1–(4 were prepared by the reaction of VOSO4·5H2O with the Schiff bases in 1:2 metal-ligand ratio while complex (5 in 2:2 metal-ligand ratio in DMF-ethanol medium. The compounds so obtained were characterized by different physico-chemical studies, such as, elemental analysis, molar conductance and magnetic measurements, infrared, ESR, thermogravimetric studies, mass and electronic spectral studies. The overall IR studies conclude that the ligand in complex (1–(4 behave as monobasic bidentate ON donor, while the ligand in the complex (5 behaves as dibasic tetradentate O2N2 donor. The 3D-molecular modeling and analysis for bond lengths and bond angles have also been carried out for two representative compounds, [VO(sal-snm2(H2O]·H2O (3 and [VO(dadps(H2O]2·2H2O (5 to substantiate the proposed structures. Based on these studies suitable octahedral structures have been proposed for these complexes.

  15. Subcellular localization and functional domain studies of DEFECTIVE KERNEL1 in maize and Arabidopsis suggest a model for aleurone cell fate specification involving CRINKLY4 and SUPERNUMERARY ALEURONE LAYER1.

    Science.gov (United States)

    Tian, Qing; Olsen, Lene; Sun, Beimeng; Lid, Stein Erik; Brown, Roy C; Lemmon, Betty E; Fosnes, Kjetil; Gruis, Darren Fred; Opsahl-Sorteberg, Hilde-Gunn; Otegui, Marisa S; Olsen, Odd-Arne

    2007-10-01

    DEFECTIVE KERNEL1 (DEK1), which consists of a membrane-spanning region (DEK1-MEM) and a calpain-like Cys proteinase region (DEK1-CALP), is essential for aleurone cell formation at the surface of maize (Zea mays) endosperm. Immunolocalization and FM4-64 dye incubation experiments showed that DEK1 and CRINKLY4 (CR4), a receptor kinase implicated in aleurone cell fate specification, colocalized to plasma membrane and endosomes. SUPERNUMERARY ALEURONE LAYER1 (SAL1), a negative regulator of aleurone cell fate encoding a class E vacuolar sorting protein, colocalized with DEK1 and CR4 in endosomes. Immunogold localization, dual-axis electron tomography, and diffusion of fluorescent dye tracers showed that young aleurone cells established symplastic subdomains through plasmodesmata of larger dimensions than those connecting starchy endosperm cells and that CR4 preferentially associated with plasmodesmata between aleurone cells. Genetic complementation experiments showed that DEK1-CALP failed to restore wild-type phenotypes in maize and Arabidopsis thaliana dek1 mutants, and DEK1-MEM also failed to restore wild-type phenotypes in Arabidopsis dek1-1 mutants. Instead, ectopic expression of DEK1-MEM under the control of the cauliflower mosaic virus 35S promoter gave a dominant negative phenotype. These data suggest a model for aleurone cell fate specification in which DEK1 perceives and/or transmits a positional signal, CR4 promotes the lateral movement of aleurone signaling molecules between aleurone cells, and SAL1 maintains the proper plasma membrane concentration of DEK1 and CR4 proteins via endosome-mediated recycling/degradation.

  16. Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways

    Directory of Open Access Journals (Sweden)

    Ferrari Stefano

    2009-12-01

    Full Text Available Abstract Background Osteosarcoma (OS is the most common primary bone tumour in children and young adults. Despite improved prognosis, metastatic or relapsed OS remains largely incurable and no significant improvement has been observed in the last 20 years. Therefore, the search for alternative agents in OS is mandatory. Results We investigated phospho-ERK 1/2, MCL-1, and phospho-Ezrin/Radixin/Moesin (P-ERM as potential therapeutic targets in OS. Activation of these pathways was shown by immunohistochemistry in about 70% of cases and in all OS cell lines analyzed. Mutational analysis revealed no activating mutations in KRAS whereas BRAF gene was found to be mutated in 4/30 OS samples from patients. Based on these results we tested the multi-kinase inhibitor sorafenib (BAY 43-9006 in preclinical models of OS. Sorafenib inhibited OS cell line proliferation, induced apoptosis and downregulated P-ERK1/2, MCL-1, and P-ERM in a dose-dependent manner. The dephosphorylation of ERM was not due to ERK inhibition. The downregulation of MCL-1 led to an increase in apoptosis in OS cell lines. In chick embryo chorioallantoic membranes, OS supernatants induced angiogenesis, which was blocked by sorafenib and it was also shown that sorafenib reduced VEGF and MMP2 production. In addition, sorafenib treatment dramatically reduced tumour volume of OS xenografts and lung metastasis in SCID mice. Conclusion In conclusion, ERK1/2, MCL-1 and ERM pathways are shown to be active in OS. Sorafenib is able to inhibit their signal transduction, both in vitro and in vivo, displaying anti-tumoural activity, anti-angiogenic effects, and reducing metastatic colony formation in lungs. These data support the testing of sorafenib as a potential therapeutic option in metastatic or relapsed OS patients unresponsive to standard treatments.

  17. [GASTROINTESTINAL INVOLVEMENT IN HUMAN BARTONELLOSIS

    Science.gov (United States)

    Maguiña, Ciro; Gotuzzo, Eduardo; Carcelén, Amador; Salinas, César; Cok, Jaime; Recavarren, Sixto; Bussalleu, Alejandro

    1997-01-01

    We present a prospective study of 68 patients with the acute phase of human bartonellosis, admitted to Cayetano Heredia National Hospital.Gastrointestinal symptoms were reported as follows: abdominal pain 46,3%, coluria 44,4%, vomiting 40,3%, jaundice 38,5%, diarrhea 29,9%, constipation 8,9%. The more common signs were pallor 97%, hepatomegaly 82%, fever 79,1%, malnutrition 75,2%, systolic heart murmur 77,9%, jaundice 71,6%, lymph node enlargement 70,1%.Signs observed during the hospital course were 29,4% lower extremities edema, 22,6% myalgia, 16,4% pericardial effusion, 16,4% generalized edema. The more common gastrointestinal signs were hepatomegaly 82%(52/68), jaundice 71,6% (48/68) and splenomegaly 29,4%(20/68).The -lower liver border was found between 1 to 4 below the lower rib border in 71,6%(48/67) and below 5 cm b. l. r. b. in 11,9%(8/67).60% had abnormal liver function tests, 54,6% had mainly direct bilirrubin elevationand 45,4% mainly indirect.SGOT was elevated in 28,5% and SGPT in 25%, 28,3% had elevated alkaline phosphatase. The bilirrubin media was 3,5 mg/dI (range 0,6-21), the indirect bilirrubin media was 1,6 mg/dI (range 0,5-11,5), the direct bilirrubin media was 1,9 mg/dI (range 0,3-18), The SGOT media 73,9 U/L (range 9-1250), SGPT media 65,5U/L (range 6-1596). Alkaline phosphatase 5,9 mui/ml (range 3-497). Albumin media 3,09 (range 2-4,2).Patients with bacterial coinfection (salmonella, staphilococcus, enterobacter, shigella) had a higher increase in bilirrubin and transaminases.Three patients had liver biopsies, two revealed Küpffer cells hyperplasia (moderate to severe), one revealed intracellular hyperplasia, one patient coinfected with diseminated hystoplasmosis had granulomas in the liver.Mortality(8,8%) was associated to hepatocellular involvement (SGOT media 330U/L, SGPT media 207 U/L, alkaline phosphatase media 183 mui/ml), hypoalbuminemia media = 2,4 gr/1) and generalized edema.

  18. Parental involvement and mental well-being of Indian adolescents.

    Science.gov (United States)

    Hasumi, Takahiro; Ahsan, Fatimah; Couper, Caitlin M; Aguayo, Jose L; Jacobsen, Kathryn H

    2012-11-01

    This study examined the association between parental involvement and mental well being among the 6721 school going adolescents aged 13 to 15 years who participated in Indias nationally representative Global School based Student Health Survey (GSHS) in 2007. Parental involvement (homework checking, parental understanding of their childrens problems, and parental knowledge of their childrens freetime activities) was reported by students to decrease with age, while poor mental health (loneliness, insomnia due to anxiety, and sadness and hopelessness) increased with age. Age adjusted Logistic regression models showed that high levels of reported parental involvement were significantly associated with a decreased likelihood of poor mental health.

  19. Patient involvement in Danish health care

    DEFF Research Database (Denmark)

    Vrangbaek, Karsten

    2015-01-01

    PURPOSE: The purpose of this paper is to investigate different types of patient involvement in Denmark, and to discuss the potential implications of pursuing several strategies for patient involvement simultaneously. DESIGN/METHODOLOGY/APPROACH: The paper presents a preliminary framework...... for analysis of patient involvement in health care. This framework is used to analyze key governance features of patient involvement in Denmark based on previous research papers and reports describing patient involvement in Danish health care. FINDINGS: Patient involvement is important in Denmark...... implications for the development of patient involvement in health care. ORIGINALITY/VALUE: This paper fulfills a need to study different types of patient involvement and to develop a theoretical framework for characterizing and analyzing such involvement strategies....

  20. Models

    DEFF Research Database (Denmark)

    Juel-Christiansen, Carsten

    2005-01-01

    Artiklen fremhæver den visuelle rotation - billeder, tegninger, modeller, værker - som det privilligerede medium i kommunikationen af ideer imellem skabende arkitekter......Artiklen fremhæver den visuelle rotation - billeder, tegninger, modeller, værker - som det privilligerede medium i kommunikationen af ideer imellem skabende arkitekter...

  1. Involving Corporate Functions: Who Contributes to Sustainable Development?

    Directory of Open Access Journals (Sweden)

    Stefan Schaltegger

    2014-05-01

    Full Text Available A large body of literature claims that corporate sustainable development is a cross-functional challenge, which requires all functional units to be involved. However, it remains uncertain to what extent and in which way different corporate functions are actually involved in corporate sustainability management. To bridge this research gap, our paper draws on a concept of involvement introduced in the field of consumer behavior. Based on this previous research, our paper distinguishes two components of involvement: first, a cognitive-affective component, incorporating being affected by sustainability issues and being supportive of corporate sustainability; and second, a behavioral component, represented by the application of sustainability management tools. We use this concept to empirically analyze the involvement of corporate functions in sustainability management and find considerable differences in large German companies. Whereas public relations and strategic management are heavily involved, finance, accounting and management control appear not to be involved. A multinomial logistic regression shows that the cognitive-affective component significantly influences the behavioral component, with a functional unit being affected influencing the application of tools the most. Building on the model proposed, the paper provides implications on how to increase a functional unit’s involvement in sustainability management.

  2. Involvement of notch signaling in wound healing.

    Directory of Open Access Journals (Sweden)

    Srinivasulu Chigurupati

    Full Text Available The Notch signaling pathway is critically involved in cell fate decisions during development of many tissues and organs. In the present study we employed in vivo and cell culture models to elucidate the role of Notch signaling in wound healing. The healing of full-thickness dermal wounds was significantly delayed in Notch antisense transgenic mice and in normal mice treated with gamma-secretase inhibitors that block proteolytic cleavage and activation of Notch. In contrast, mice treated with a Notch ligand Jagged peptide showed significantly enhanced wound healing compared to controls. Activation or inhibition of Notch signaling altered the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in a scratch wound healing model in ways consistent with roles for Notch signaling in wound healing functions all three cell types. These results suggest that Notch signaling plays important roles in wound healing and tissue repair, and that targeting the Notch pathway might provide a novel strategy for treatment of wounds and for modulation of angiogenesis in other pathological conditions.

  3. Genes involved in cell division in mycoplasmas

    Directory of Open Access Journals (Sweden)

    Frank Alarcón

    2007-01-01

    Full Text Available Bacterial cell division has been studied mainly in model systems such as Escherichia coli and Bacillus subtilis, where it is described as a complex process with the participation of a group of proteins which assemble into a multiprotein complex called the septal ring. Mycoplasmas are cell wall-less bacteria presenting a reduced genome. Thus, it was important to compare their genomes to analyze putative genes involved in cell division processes. The division and cell wall (dcw cluster, which in E. coli and B. subtilis is composed of 16 and 17 genes, respectively, is represented by only three to four genes in mycoplasmas. Even the most conserved protein, FtsZ, is not present in all mycoplasma genomes analyzed so far. A model for the FtsZ protein from Mycoplasma hyopneumoniae and Mycoplasma synoviae has been constructed. The conserved residues, essential for GTP/GDP binding, are present in FtsZ from both species. A strong conservation of hydrophobic amino acid patterns is observed, and is probably necessary for the structural stability of the protein when active. M. synoviae FtsZ presents an extended amino acid sequence at the C-terminal portion of the protein, which may participate in interactions with other still unknown proteins crucial for the cell division process.

  4. The emotional involvement in the workplace: An empirical study

    Directory of Open Access Journals (Sweden)

    Ana María Lucia-Casademunt

    2012-06-01

    Full Text Available Purpose: In a multitude of studies, it is verified that the generation of positive attitudes for employees such as job satisfaction or job involvement, have a positive influence on productivity levels of companies. The current investigation focus on the identification of employee-profile -who is emotionally involved with their work activity- through the use of a set of individual, job related and attitudinal factors.Design/methodology: A review of the literature about the main factors that affect the job involvement particularly on its emotional dimension has been completed. For its measurement at the empirical level, various items related to psychological well being of employees included in the IV European Working Conditions Survey-2010 are used. Moreover, those items are identified in Job Involvement Questionnaire (Lodahl & Kejner, 1965. Since then, an empirical and multidimensional study is carried out by applying a logistic regression model on the sample of 11,149 employees obtained with European survey cited previously.Findings: The logistic regression model identifies the factors, which are directly related to emotional involvement at the workplace. Ultimately, is raised a definitive model that define the European employee-profile -who is emotionally involved at the workplace-: a rather aged person who has been working at his/her present place of employment for several years in a medium-sized company where possibly there exist a good working relationship between workers and their superiors –social support-. These employees are “white-collar” workers, have career advancement opportunities in the organizational hierarchy. They perform variety, flexible and complex tasks, which leads to satisfaction in terms of pay and working conditions.Research limitations/implications: Emotional involvement has been measured through self-awareness and, therefore, the corresponding bias in the key variable must be assumed. In addition, the casual

  5. Problems and Challenges for Cosmology involving Massive Neutrinos

    CERN Document Server

    Krauss, L M

    1996-01-01

    I review the challenges and problems facing the standard cosmological model, involving an $\\Omega=1$ Universe dominated by non-baryonic dark matter, which arise due to: age estimates of the universe, estimates of the baryon fraction of the universe, and structure formation. Certain of these problems are exacerbated, and certain of these are eased, by the inclusion of some component to the energy density of matter from massive neutrinos. I conclude with a comparison of the two favored current cosmological models, involving either a mixture of cold dark matter and hot dark matter, or the inclusion of a cosmological constant.

  6. The role of Customer Involvement in Library E-services

    DEFF Research Database (Denmark)

    Scupola, Ada; Nicolajsen, Hanne Westh

    2009-01-01

    We investigate customer involvement in the development of e-service within research Libraries. By revisiting earlier research on innovation processes as well as newer research on new product and new service development we derive a conceptual model on different actors that are important in the pro......We investigate customer involvement in the development of e-service within research Libraries. By revisiting earlier research on innovation processes as well as newer research on new product and new service development we derive a conceptual model on different actors that are important...

  7. Quality assurance - how to involve the employees

    DEFF Research Database (Denmark)

    Jørgensen, Michael Søgaard

    1996-01-01

    An overview of strategies for involvement of employees in quality assurance developement and implementation.......An overview of strategies for involvement of employees in quality assurance developement and implementation....

  8. Cyber Incidents Involving Control Systems

    Energy Technology Data Exchange (ETDEWEB)

    Robert J. Turk

    2005-10-01

    The Analysis Function of the US-CERT Control Systems Security Center (CSSC) at the Idaho National Laboratory (INL) has prepared this report to document cyber security incidents for use by the CSSC. The description and analysis of incidents reported herein support three CSSC tasks: establishing a business case; increasing security awareness and private and corporate participation related to enhanced cyber security of control systems; and providing informational material to support model development and prioritize activities for CSSC. The stated mission of CSSC is to reduce vulnerability of critical infrastructure to cyber attack on control systems. As stated in the Incident Management Tool Requirements (August 2005) ''Vulnerability reduction is promoted by risk analysis that tracks actual risk, emphasizes high risk, determines risk reduction as a function of countermeasures, tracks increase of risk due to external influence, and measures success of the vulnerability reduction program''. Process control and Supervisory Control and Data Acquisition (SCADA) systems, with their reliance on proprietary networks and hardware, have long been considered immune to the network attacks that have wreaked so much havoc on corporate information systems. New research indicates this confidence is misplaced--the move to open standards such as Ethernet, Transmission Control Protocol/Internet Protocol, and Web technologies is allowing hackers to take advantage of the control industry's unawareness. Much of the available information about cyber incidents represents a characterization as opposed to an analysis of events. The lack of good analyses reflects an overall weakness in reporting requirements as well as the fact that to date there have been very few serious cyber attacks on control systems. Most companies prefer not to share cyber attack incident data because of potential financial repercussions. Uniform reporting requirements will do much to make this

  9. 36 CFR 1010.12 - Public involvement.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Public involvement. 1010.12 Section 1010.12 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010.12 Public involvement. The Trust will make public involvement an essential part of its environmental review...

  10. Community Involvement and Disadvantaged Students: A Review.

    Science.gov (United States)

    Nettles, Saundra Murray

    1991-01-01

    Community involvement is conceptualized as a typology of the following processes of social change: (1) conversion; (2) mobilization; (3) allocation of resources; and (4) instruction. The effects of these forms of involvement are considered in a review of 13 evaluations of programs for disadvantaged youth involving the community. (SLD)

  11. Involving Nepali academics in health research

    DEFF Research Database (Denmark)

    Neupane, Dinesh; van Teijlingen, E; Khanal, V;

    2013-01-01

    Many academics from Nepal do not involve in research activities. There are several factors hindering the involvement such as inadequate human resources and lack of financial resources. Despite limited human and financial resources, we believe it is still possible to attract many Nepali academics...... in health research. This paper purposes some ideas to increase involvement of Nepali academics in health research....

  12. Parental Involvement in Traditional and Online Education

    Science.gov (United States)

    Chang, Cheng-Sian; Chen, Hsi-Mei

    2011-01-01

    While parental involvement benefits the learning performance of elementary students and the internet changes the learning environment, few studies have examined how parents are involved in the virtual world. This two-year project analysed the effects of parental involvement at home, in school and on internet use. The first stage of our research…

  13. Parental Involvement in Special Education Curriculum

    Science.gov (United States)

    Westwood-Robinette, Nicole M.

    2014-01-01

    Educators and researchers have long considered parental involvement an integral part in the success of students and researchers have concluded that there is a connection between parental involvement and the retention rates of students who are involved in regular education curriculum. However, much less information is available regarding the…

  14. In vitro model suggests oxidative stress involved in keratoconus disease

    Science.gov (United States)

    Karamichos, D.; Hutcheon, A. E. K.; Rich, C. B.; Trinkaus-Randall, V.; Asara, J. M.; Zieske, J. D.

    2014-04-01

    Keratoconus (KC) affects 1:2000 people and is a disorder where cornea thins and assumes a conical shape. Advanced KC requires surgery to maintain vision. The role of oxidative stress in KC remains unclear. We aimed to identify oxidative stress levels between human corneal keratocytes (HCKs), fibroblasts (HCFs) and keratoconus cells (HKCs). Cells were cultured in 2D and 3D systems. Vitamin C (VitC) and TGF-β3 (T3) were used for 4 weeks to stimulate self-assembled extracellular matrix (ECM). No T3 used as controls. Samples were analyzed using qRT-PCR and metabolomics. qRT-PCR data showed low levels of collagen I and V, as well as keratocan for HKCs, indicating differentiation to a myofibroblast phenotype. Collagen type III, a marker for fibrosis, was up regulated in HKCs. We robustly detected more than 150 metabolites of the targeted 250 by LC-MS/MS per condition and among those metabolites several were related to oxidative stress. Lactate levels, lactate/malate and lactate/pyruvate ratios were elevated in HKCs, while arginine and glutathione/oxidized glutathione ratio were reduced. Similar patterns found in both 2D and 3D. Our data shows that fibroblasts exhibit enhanced oxidative stress compared to keratocytes. Furthermore the HKC cells exhibit the greatest level suggesting they may have a myofibroblast phenotype.

  15. Inquiry Role Approach: A Model for Counselor Involvement in Learning.

    Science.gov (United States)

    Bingman, Richard M.; And Others

    The Inquiry Role Approach (IRA) is a strategy for classroom learning in which students work as 4-member teams and assume roles as Team Coordinator, Process Advisor, Data Recorder, and Technical Advisor. Cognitive as well as affective objectives are identified which relate to optimum learning and personal growth in the classroom. The counselor's…

  16. Parent involvement and student academic performance: a multiple mediational analysis.

    Science.gov (United States)

    Topor, David R; Keane, Susan P; Shelton, Terri L; Calkins, Susan D

    2010-01-01

    Parent involvement in a child's education is consistently found to be positively associated with a child's academic performance. However, there has been little investigation of the mechanisms that explain this association. The present study examines two potential mechanisms of this association: the child's perception of cognitive competence and the quality of the student-teacher relationship. This study used a sample of 158 seven-year-old participants, their mothers, and their teachers. Results indicated a statistically significant association between parent involvement and a child's academic performance, over and above the impact of the child's intelligence. A multiple mediation model indicated that the child's perception of cognitive competence fully mediated the relation between parent involvement and the child's performance on a standardized achievement test. The quality of the student-teacher relationship fully mediated the relation between parent involvement and teacher ratings of the child's classroom academic performance. Limitations, future research directions, and implications for public policy initiatives are discussed.

  17. Democratizing Process Innovation? On Citizen Involvement in Public Sector BPM

    Science.gov (United States)

    Niehaves, Björn; Malsch, Robert

    ‘Open Innovation’ has been heavily discussed for product innovations; however, an information systems (IS) perspective on ‘process innovation’ has not yet been taken. Analyzing the example of the public sector in Germany, the paper seeks to investigate the factors that hinder and support ‘open process innovation’, a concept we define as the involvement of citizens in business process management (BPM) activities. With the help of a quantitative study (n=358), six factors are examined for their impact on citizen involvement in local government BPM initiatives. The results show that citizen involvement in reform processes is not primarily motivated by the aim of cost reduction, but rather related to legitimacy reasons and the intent to increase employee motivation. Based on these findings, implications for (design) theory and practice are discussed: Instead of detailed collaborative business processes modeling, the key of citizen involvement in public sector BPM lies in communication and mutual understanding.

  18. Involvement and Loyalty in Recreation Swimming in Greece: Investigating Relationships

    Directory of Open Access Journals (Sweden)

    Evangelia Kontogianni

    2011-12-01

    Full Text Available Present study tested the validity of involvement scale (Kyle et al., 2004, examined differences according demographic characteristics and investigated possible relationships between involvement and attitudinal loyalty in context of recreational swimming. Three hundred and forty nine participants (61.9% females from a major swimming sport center in northern Greece, completed the three dimensional involvement model of Kyle’s et al (2004, and Armitage & Conner’s (1999 attitudinal loyalty’s instrument. Demographics of the sample and frequency of participation were also recorded. The results indicated high differences (p<.01 between dimensions of involvement and the frequency of participation levels supporting the predictive validity of the scale. Female subgroup and married subgroup scored significantly higher in all involvement dimensions (attraction, centrality, self-expression than males and singles respectively. Significant statistical differences existed also between involvement dimensions and age subgroups. Finally, involvement concept only partially (centrality, β=.13 and attraction, β=.47 dimensions predicted swimmers loyalty (p<.001. Marketing implications are discussed toward the development of appropriate promotion strategies from sport managers toward overcoming swimmer’s needs and broadening participants net.

  19. Across frequency processes involved in auditory detection of coloration

    DEFF Research Database (Denmark)

    Buchholz, Jörg; Kerketsos, P

    2008-01-01

    When an early wall reflection is added to a direct sound, a spectral modulation is introduced to the signal's power spectrum. This spectral modulation typically produces an auditory sensation of coloration or pitch. Throughout this study, auditory spectral-integration effects involved in coloration...... detection are investigated. Coloration detection thresholds were therefore measured as a function of reflection delay and stimulus bandwidth. In order to investigate the involved auditory mechanisms, an auditory model was employed that was conceptually similar to the peripheral weighting model [Yost, JASA......, 1982, 416-425]. When a “classical” gammatone filterbank was applied within this spectrum-based model, the model largely underestimated human performance at high signal frequencies. However, this limitation could be resolved by employing an auditory filterbank with narrower filters. This novel...

  20. Modelling

    CERN Document Server

    Spädtke, P

    2013-01-01

    Modeling of technical machines became a standard technique since computer became powerful enough to handle the amount of data relevant to the specific system. Simulation of an existing physical device requires the knowledge of all relevant quantities. Electric fields given by the surrounding boundary as well as magnetic fields caused by coils or permanent magnets have to be known. Internal sources for both fields are sometimes taken into account, such as space charge forces or the internal magnetic field of a moving bunch of charged particles. Used solver routines are briefly described and some bench-marking is shown to estimate necessary computing times for different problems. Different types of charged particle sources will be shown together with a suitable model to describe the physical model. Electron guns are covered as well as different ion sources (volume ion sources, laser ion sources, Penning ion sources, electron resonance ion sources, and H$^-$-sources) together with some remarks on beam transport.