WorldWideScience

Sample records for pathway effective public

  1. Public relations effectiveness in public health institutions.

    Science.gov (United States)

    Springston, Jeffrey K; Weaver Lariscy, Ruth Ann

    2005-01-01

    This article explores public relations effectiveness in public health institutions. First, the two major elements that comprise public relations effectiveness are discussed: reputation management and stakeholder relations. The factors that define effective reputation management are examined, as are the roles of issues and crisis management in building and maintaining reputation. The article also examines the major facets of stakeholder relations, including an inventory of stakeholder linkages and key audiences, such as the media. Finally, methods of evaluating public relations effectiveness at both the program level and the institutional level are explored.

  2. Effective Public Management

    Science.gov (United States)

    Bower, Joseph L.

    1977-01-01

    Argues that public management differs from private management not just in degree but in quality, so that American business is an inappropriate analogy for evaluating public management. In particular, "purpose,""organization," and "people" have different meaning and significance in public agencies and private businesses. (JG)

  3. A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways

    Science.gov (United States)

    Han, Junwei; Li, Chunquan; Yang, Haixiu; Xu, Yanjun; Zhang, Chunlong; Ma, Jiquan; Shi, Xinrui; Liu, Wei; Shang, Desi; Yao, Qianlan; Zhang, Yunpeng; Su, Fei; Feng, Li; Li, Xia

    2015-01-01

    Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI). PMID:25551156

  4. 75 FR 61497 - Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing; Request...

    Science.gov (United States)

    2010-10-05

    ... Price Competition and Innovation Act of 2009 (BPCI Act) that amends the Public Health Service Act (PHS... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0477] Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing; Request for...

  5. Differential genomic effects on signaling pathways by two different CeO2 nanoparticles in HepG2 cells

    Data.gov (United States)

    U.S. Environmental Protection Agency — Differential genomic effects on signaling pathways by two different CeO2 nanoparticles in HepG2 cells. This dataset is associated with the following publication:...

  6. Policy Pathways: Joint Public-Private Approaches for Energy Efficiency Finance

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-09-06

    This Policy Pathway outlines, through the experiences and lessons learned from country examples, the critical elements to put in place a public-private partnership to finance energy efficiency. It focuses on three mechanisms - dedicated credit lines, risk guarantees, and energy performance service contracts and presents the planning, implementing, monitoring, and evaluating phases of implemention. Accelerating and scaling up private investment in energy efficiency is crucial to exploit the potential of energy efficiency. However many barriers remain to private investment such as access to capital, uncertainty of future energy prices, transaction costs, perceived higher risk, and lack of knowledge. As part of the IEA 25 Energy Efficiency Policy Recommendations, the IEA recommends that governments support private investment in energy efficiency. A joint public-private approach can use public finance and regulatory policy to support the scaling up of private investment in energy efficiency.

  7. The Cardiopulmonary Effects of Ambient Air Pollution and Mechanistic Pathways: A Comparative Hierarchical Pathway Analysis

    Science.gov (United States)

    Thomas, Duncan C.; Zhang, Junfeng; Kipen, Howard M.; Rich, David Q.; Zhu, Tong; Huang, Wei; Hu, Min; Wang, Guangfa; Wang, Yuedan; Zhu, Ping; Lu, Shou-En; Ohman-Strickland, Pamela; Diehl, Scott R.; Eckel, Sandrah P.

    2014-01-01

    Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001) and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005). These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours) and the hemostasis pathway responds gradually over a 2–3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system. PMID:25502951

  8. The cardiopulmonary effects of ambient air pollution and mechanistic pathways: a comparative hierarchical pathway analysis.

    Directory of Open Access Journals (Sweden)

    Ananya Roy

    Full Text Available Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001 and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005. These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours and the hemostasis pathway responds gradually over a 2-3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system.

  9. Creating Pathways to Jobs through Public-Private Partnerships: The Demands of the Workplace.

    Science.gov (United States)

    McCain, Mary

    1998-01-01

    Workplace demands for high skills, adaptability, and continuous learning require public-private partnerships to develop effective training systems. Partnerships should serve the interests of all stakeholders, establish skills and certification standards, and create infrastructures for access. (SK)

  10. Effective Instruction of Public Speaking

    OpenAIRE

    竹野, 茂; Shigeru, TAKENO

    2012-01-01

    This paper explores the instruction of public speaking in a large-size class. The author has been in charge of the speech classes,SPEECH III and SPEECH IV mainly for the second year students at Miyazaki Municipal University for several years. At the preparation stage of SPEECH III, and IV, he intended that the class size was about 30 students as one group in the lecture style. But, in reality, more than 50 students took the course. Then he had to rethink the way of teaching. To solve the prob...

  11. overhauling the national industrial court act: a pathway to effective ...

    African Journals Online (AJOL)

    DJFLEX

    GLOBAL JOURNAL OF SOCIAL SCIENCES VOL 9, NO. 1, 2010: ... PATHWAY TO EFFECTIVE LABOUR DISPUTE SETTLEMENT IN ... For more than four (4) decades, labour ... settlement machinery provides meaningful approach to ..... economy. The National Industrial Court Act 2006 would have very positive effect on our ...

  12. Public Knowledge, Private Minds: Meaning Making on the Pathways of Science Communication

    Science.gov (United States)

    Davis, Pryce R.

    Every day people are inundated with news reports about the latest scientific research. The ways in which these texts enlighten or misinform the general public is a central question in both the research literature and discussions in popular culture. However, both research and popular discussion often take on deficit views of these texts, and the capabilities of readers to critically engage with them, and treat them as static, one-way conduits that transfer information to a passive audience. In contrast, I advocate treating popular science texts as the result of a chain of consumption and production that are actively shaped by the varied perspectives of scientists, communicators, and members of the general public. My work envisions all of these actors as science learners who simultaneously act as both producers and consumers of science, and who interact with one another through in-the-moment meaning making. This dissertation examines how the meaning of scientific research is filtered and transformed in moments of interaction and knowledge construction as it moves along this pathway of science communication from scientists to the general public. I present the results of a study that attempts to follow pieces of recent scientific research as they work their way from scientists to publication as popular science news stories, and ultimately to the public. To that end, I collected data from three types of actors involved in the paths of science communication, as well as the texts they read and generate. These actors include (1) the scientists who performed the research, (2) the reporters tasked with writing about it for popular dissemination, and (3) members of the public who must read and interpret the research. The texts I analyze include: peer-reviewed scientific journal articles, university-produced news briefs, popular press science stories, and various text-based conversations between scientists and reporters. Through an analysis of texts, individual interviews, and

  13. Attentional effects in the visual pathways

    DEFF Research Database (Denmark)

    Bundesen, Claus; Larsen, Axel; Kyllingsbæk, Søren

    2002-01-01

    nucleus. Frontal activations were found in a region that seems implicated in visual short-term memory (posterior parts of the superior sulcus and the middle gyrus). The reverse, color-shape comparison showed bilateral increases in rCBF in the anterior cingulate gyri, superior frontal gyri, and superior...... and middle temporal gyri. The attentional effects found by the shape-color comparison in the thalamus and the primary visual cortex may have been generated by feedback signals preserving visual representations of selected stimuli in short-term memory....

  14. Effect of overall feedback inhibition in unbranched biosynthetic pathways.

    Science.gov (United States)

    Alves, R; Savageau, M A

    2000-11-01

    We have determined the effects of control by overall feedback inhibition on the systemic behavior of unbranched metabolic pathways with an arbitrary pattern of other feedback inhibitions by using a recently developed numerical generalization of Mathematically Controlled Comparisons, a method for comparing the function of alternative molecular designs. This method allows the rigorous determination of the changes in systemic properties that can be exclusively attributed to overall feedback inhibition. Analytical results show that the unbranched pathway can achieve the same steady-state flux, concentrations, and logarithmic gains with respect to changes in substrate, with or without overall feedback inhibition. The analytical approach also shows that control by overall feedback inhibition amplifies the regulation of flux by the demand for end product while attenuating the sensitivity of the concentrations to the same demand. This approach does not provide a clear answer regarding the effect of overall feedback inhibition on the robustness, stability, and transient time of the pathway. However, the generalized numerical method we have used does clarify the answers to these questions. On average, an unbranched pathway with control by overall feedback inhibition is less sensitive to perturbations in the values of the parameters that define the system. The difference in robustness can range from a few percent to fifty percent or more, depending on the length of the pathway and on the metabolite one considers. On average, overall feedback inhibition decreases the stability margins by a minimal amount (typically less than 5%). Finally, and again on average, stable systems with overall feedback inhibition respond faster to fluctuations in the metabolite concentrations. Taken together, these results show that control by overall feedback inhibition confers several functional advantages upon unbranched pathways. These advantages provide a rationale for the prevalence of this

  15. Assessing Natural Direct and Indirect Effects Through Multiple Pathways

    DEFF Research Database (Denmark)

    Lange, T; Rasmussen, M; Thygesen, Lau Caspar

    2014-01-01

    . The approach is an extension of the natural effect models proposed by Lange et al. (Am J Epidemiol. 2012;176(3):190-195). By allowing the analysis of distinct multiple pathways, the suggested approach adds to the capabilities of modern mediation techniques. Furthermore, the approach can be implemented using......Within the fields of epidemiology, interventions research and social sciences researchers are often faced with the challenge of decomposing the effect of an exposure into different causal pathways working through defined mediator variables. The goal of such analyses is often to understand...... the mechanisms of the system or to suggest possible interventions. The case of a single mediator, thus implying only 2 causal pathways (direct and indirect) from exposure to outcome, has been extensively studied. By using the framework of counterfactual variables, researchers have established theoretical...

  16. Protective effect of resveratrol against nigrostriatal pathway injury in striatum via JNK pathway.

    Science.gov (United States)

    Li, Dan; Liu, Nan; Zhao, Liang; Tong, Lei; Kawano, Hitoshi; Yan, Hong-Jing; Li, Hong-Peng

    2017-01-01

    Nigrostriatal pathway injury is one of the traumatic brain injury models that usually lead to neurological dysfunction or neuron necrosis. Resveratrol-induced benefits have recently been demonstrated in several models of neuronal degeneration diseases. However, the protective properties of resveratrol against neurodegeneration have not been explored definitely. Thus, we employ the nigrostriatal pathway injury model to mimic the insults on the brain. Resveratrol decreased the p-ERK expression and increased the p-JNK expression compared to the DMSO group, but not alter the p38 MAPK proteins around the lesion site by Western blot. Prior to the injury, mice were infused with resveratrol intracerebroventricularly with or without JNK-IN-8, a specific c-JNK pathway inhibitor for JNK1, JNK2 and JNK4. The study assessed modified improved neurological function score (mNSS) and beam/walking test, the level of inflammatory cytokines IL-1β, IL-6 and TNF-α, and striatal expression of Bax and Bcl-2 proteins associated with neuronal apoptosis. The results revealed that resveratrol exerted a neuroprotective effect as shown by the improved mNSS and beam latency, anti-inflammatory effects as indicated by the decreased level of IL-1β, TNF-α and IL-6. Furthermore, resveratrol up-regulated the protein expression of p-JNK and Bcl-2, down-regulated the expression of Bax and the number of Fluoro-Jade C (FJC) positive neurons. However, these advantages of resveratrol were abolished by JNK-IN-8 treatment. Overall, we demonstrated that resveratrol treatment attenuates the nigrostriatal pathway injury-induced neuronal apoptosis and inflammation via activation of c-JNK signaling. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Quality Tuberculosis Care in Indonesia: Using Patient Pathway Analysis to Optimize Public-Private Collaboration.

    Science.gov (United States)

    Surya, Asik; Setyaningsih, Budiarti; Suryani Nasution, Helmi; Gita Parwati, Cicilia; Yuzwar, Yullita E; Osberg, Mike; Hanson, Christy L; Hymoff, Aaron; Mingkwan, Pia; Makayova, Julia; Gebhard, Agnes; Waworuntu, Wiendra

    2017-11-06

    Tuberculosis (TB) is the fourth leading cause of death in Indonesia. In 2015, the World Health Organization estimated that nearly two-thirds of the TB patients in Indonesia had not been notified, and the status of their care remained unknown. As such, Indonesia is home to nearly 20% of the world's "missing" TB patients. Understanding where patients go for care may enable strategic planning of services to better reach them. A patient pathway analysis (PPA) was conducted to assess the alignment between patient care seeking and the availability of TB diagnostic and treatment services at the national and subnational level in Indonesia. The PPA results revealed that only 20% of patients encountered diagnostic capacity at the location where they first sought care. Most initial care seeking occurred in the private sector and case notification lagged behind diagnostic confirmation in the public sector. The PPA results emphasize the role that the private sector plays in TB patient care seeking and suggested a need for differentiated approaches, by province, to respond to variances in care-seeking patterns and the capacities of public and private providers. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  18. Effects of Sunphenon and Polyphenon 60 on proteolytic pathways ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... The effect of Sunphenon and Polyphenon 60 in oxidative stress response, myogenic regulatory factors, inflammatory cytokines, apoptotic and proteolytic pathways on H2O2-induced myotube atrophy was addressed. Cellular responses of H2O2-induced C2C12cells were examined, including mRNA ...

  19. Measuring effects of public procurement of innovation

    DEFF Research Database (Denmark)

    Rolfstam, Max

    Underway for quite some time now has been the discussion on using public procurement as a means to stimulate innovation. However - with some exceptions this has been mainly a conceptual discussion vastly surpassed a corresponding development of appropriate monitoring tools. Also, even if both...... qualitative and quantitative studies have been made, they tend to lack connection to the underlying mechanisms envisaged in the conceptual and/or case based literature. A challenge in this endeavour prevails in the nature of how public procurement of innovation works. Some of the effects rendered may...... about the usefulness of public procurement of innovation are at all realistic and feasible in practice. After reviewing different currently available means to measure both public procurement of innovation measures, as well as public procurement of innovation, the paper outlines a case-based approach...

  20. Integrating publicly-available data to generate computationally-predicted adverse outcome pathways for hepatic steatosis

    Science.gov (United States)

    The adverse outcome pathway (AOP) framework provides a way of organizing knowledge related to the key biological events that result in a particular health outcome. For the majority of environmental chemicals, the availability of curated pathways characterizing potential toxicity ...

  1. The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative pathway amplification

    DEFF Research Database (Denmark)

    Harboe, Morten; Garred, Peter; Karlstrøm, Ellen

    2009-01-01

    Complement activation plays an important role in human pathophysiology. The effect of classical pathway activation is largely dependent on alternative pathway (AP) amplification, whereas the role of AP for the down-stream effect of mannan-induced lectin pathway (LP) activation is poorly understood...... that AP amplification is quantitatively responsible for the final effect of initial specific LP activation. TCC generation on the solid phase was distinctly but less inhibited by anti-fD. C2 bypass of the LP pathway could be demonstrated, and AP amplification was also essential during C2 bypass in LP...... as shown by complete inhibition of TCC generation in C2-deficient serum by anti-fD and anti-properdin antibodies. In conclusion, the down-stream effect of LP activation depends strongly on AP amplification in normal human serum and in the C2 bypass pathway....

  2. Message Effects of Public Service Advertising.

    Science.gov (United States)

    Lynn, Jerry R.

    Public service advertisements, disseminated via the mass media, have been credited with "positive attitudinal effects" in past research, but only certain kinds of such advertisements are really effective. Of the types of appeals used in television commercials--informative, emotional, "establishment" (or status quo), and…

  3. Chernobyl: the effects on public health?

    Energy Technology Data Exchange (ETDEWEB)

    Aurengo, A. [Hopital Pitie-Salpetriere, Dept. Nucleaire Medecine, 75 - Paris (France)

    2003-07-01

    Because of its public health, ecological and industrial consequences, the Chernobyl accident has become a myth which serves as the focus of many fears, justified or not. no one can question the seriousness of the event, but after fifteen years there is still no agreement about the effect it has had or will have on public health. For example, the total number of deaths attributed to Chernobyl varies from less than a hundred to several millions and congenital malformations from negligible to cataclysmic. Effects on public health may be calculated from data on contamination, from the dose received and from the risk, all three of which are likely to be very roughly known; or they may be evaluated on the spot, either by epidemiological studies or by examining medical registers. This report makes an inventory of the different risks and takes stock on them. (N.C.)

  4. Effect of Managers on Public Service Performance

    DEFF Research Database (Denmark)

    Mikkelsen, Maria Falk

    This report provides an overview of the PhD dissertation “Effects of Managers on Public Service Performance” carried out at the Department of Political Science, Aarhus University and SFI – The Danish National Centre for Social Research. The dissertation is part of the research project “School...... Management, Teaching, and Student Performance” supported by the Danish Strategic Research Council (now Innovation Fund Denmark) and headed by professor Søren Winter. The dissertation explores the effects of managers on public service performance. By combining theoretical insights and research designs from......?”, “How can we improve organizational performance?”, and “How can we measure public service performance?” The setting for the dissertation is Danish middle schools (folkeskoler). The education system is generally considered an important service area as it affects later life outcomes of individual children...

  5. Chernobyl: the effects on public health?

    International Nuclear Information System (INIS)

    Aurengo, A.

    2003-01-01

    Because of its public health, ecological and industrial consequences, the Chernobyl accident has become a myth which serves as the focus of many fears, justified or not. no one can question the seriousness of the event, but after fifteen years there is still no agreement about the effect it has had or will have on public health. For example, the total number of deaths attributed to Chernobyl varies from less than a hundred to several millions and congenital malformations from negligible to cataclysmic. Effects on public health may be calculated from data on contamination, from the dose received and from the risk, all three of which are likely to be very roughly known; or they may be evaluated on the spot, either by epidemiological studies or by examining medical registers. This report makes an inventory of the different risks and takes stock on them. (N.C.)

  6. A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.

    Science.gov (United States)

    Lee, Jae Man; Lee, Yoon Kwang; Mamrosh, Jennifer L; Busby, Scott A; Griffin, Patrick R; Pathak, Manish C; Ortlund, Eric A; Moore, David D

    2011-05-25

    Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.

  7. Effect of nuclear education on public attitude

    International Nuclear Information System (INIS)

    Ohnishi, Teruaki

    1995-01-01

    A method is proposed to assess the effect of nuclear education. In this method, the nuclear education is treated as a part of the activities for public acceptance (PA), and a unit PA activity is assumed to give the same effect on the public, in essence, as a unit of nuclear information given by the newsmedia. Moreover, the change of attitude to nuclear energy is assumed to originate from enhanced understanding which, in turn, is brought by the stimulus given by the nuclear education. With the values of constants determined by using the data in Japan, example calculations were made for the educational time b 0 and the infiltration rate of education into minors B as parameters. It became clear from this calculation that the attitude to nuclear energy formed in the age of school children plays an essential role in shaping future public opinion since it is held in individuals without any notable modification for a long time after its formation, and that the effect of nuclear education to minors emerges depending on the variables b 0 and B in a highly non-linear manner. It was also found that there exists an optimum condition for nuclear education to attain the maximum amelioration of public opinion under a given condition of man-power for educational workers. (author)

  8. Effects of visceral adiposity on glycerol pathways in gluconeogenesis.

    Science.gov (United States)

    Neeland, Ian J; Hughes, Connor; Ayers, Colby R; Malloy, Craig R; Jin, Eunsook S

    2017-02-01

    To determine the feasibility of using oral 13 C labeled glycerol to assess effects of visceral adiposity on gluconeogenic pathways in obese humans. Obese (BMI ≥30kg/m 2 ) participants without type 2 diabetes underwent visceral adipose tissue (VAT) assessment and stratification by median VAT into high VAT-fasting (n=3), low VAT-fasting (n=4), and high VAT-refed (n=2) groups. Participants ingested [U- 13 C 3 ] glycerol and blood samples were subsequently analyzed at multiple time points over 3h by NMR spectroscopy. The fractions of plasma glucose (enrichment) derived from [U- 13 C 3 ] glycerol via hepatic gluconeogenesis, pentose phosphate pathway (PPP), and tricarboxylic acid (TCA) cycle were assessed using 13 C NMR analysis of glucose. Mixed linear models were used to compare 13 C enrichment in glucose between groups. Mean age, BMI, and baseline glucose were 49years, 40.1kg/m 2 , and 98mg/dl, respectively. Up to 20% of glycerol was metabolized in the TCA cycle prior to gluconeogenesis and PPP activity was minor (gluconeogenesis from glycerol in obese humans. Our findings provide preliminary evidence that excess visceral fat disrupts multiple pathways in hepatic gluconeogenesis from glycerol. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. More effective public communication - HLW disposal

    International Nuclear Information System (INIS)

    Green, J.W. Jr.

    1982-01-01

    Credibility can be enhanced and communication can be made somewhat more effective by informally talking to a small group of people as opposed to speaking to large groups. The more informal the situation can be, and the approximation of a one-to-one speaker-to-audience ratio assists the audience in obtaining a feeling they are being treated equitably. This also assists the speaker in getting a feel for the chief concerns of that particular audience. The authors have also found that this same principle has worked rather well in dealing with the media. So far they have experienced fewer mistakes and fewer sensationalisms from the media personnel with which they have had the opportunity to sit down one-on-one and explain the program. The media reaches a much greater segment of the public than any of us as individuals, and an informed media can communicate much more effectively with the public than an uninformed one

  10. Effects of participating in public conversation groups

    Directory of Open Access Journals (Sweden)

    Beatriz Adolfo

    2016-11-01

    Full Text Available The aim of this research was to analyze the effects of the participation of health, education and religious professionals in public conversation groups with LGBT people. Participants were interviewed some weeks after the groups for feedback. Professionals declared that this dialogic method (known as Public Conversations Project allowed a qualification of their practices, awareness about the challenges of talking about gender and sexual diversity at their professional’s contexts, and a broader contact with narratives of violence and discrimination against LGBT people. The structure of dialogue allowed participants to talk and listen in a less evaluative context. Differences in the effects produced by each group are discussed in relation to the differences in the group composition and to the specificities of the health, educational and religious contexts.

  11. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

    Science.gov (United States)

    Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Harsha, Choudhary; Banik, Kishore; Gupta, Subash C; Aggarwal, Bharat B

    2017-08-01

    Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  12. Heterogeneous Effects of Direct Hypoxia Pathway Activation in Kidney Cancer.

    Directory of Open Access Journals (Sweden)

    Rafik Salama

    Full Text Available General activation of hypoxia-inducible factor (HIF pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumor suppressor. However HIF-1α and HIF-2α have contrasting effects on experimental tumor progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1α and HIF-2α and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of canonical and non-canonical HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1α-specific binding, and genes associated with favorable prognosis and between HIF-2α-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-α isoform contributes a highly complex mix of pro- and anti-tumorigenic effects.

  13. Uptake of chemicals from indoor air: Pathways and health effects

    DEFF Research Database (Denmark)

    Bekö, Gabriel

    2016-01-01

    Building occupants are exposed to manufactured chemicals. Exposure in the indoor environment can occur via non-dietary ingestion (e.g. indoor dust), inhalation and dermal absorption including dermal uptake directly from air. The extent of dermal uptake from air has been previously studied...... for volatile organic compounds (VOC). Not much is however known about its role for semivolatile organics (SVOC) and therefore this exposure pathway is often neglected in exposure assessments. Dermal uptake received attention with regards to contact transfer from contaminated surfaces. Recent modeling efforts...... intake from inhalation. Further experiments have been conducted with nicotine and the results are similar. Some of the SVOCs present indoors may have adverse health effects or are categorized as potential endocrine-disrupting compounds. It has been suggested that the health effects of a chemical may...

  14. Different forms of effective connectivity in primate frontotemporal pathways.

    Science.gov (United States)

    Petkov, Christopher I; Kikuchi, Yukiko; Milne, Alice E; Mishkin, Mortimer; Rauschecker, Josef P; Logothetis, Nikos K

    2015-01-23

    It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex.

  15. Osmolyte Effects on the Unfolding Pathway of β-Lactoglobulin

    International Nuclear Information System (INIS)

    Meng Wei; Pan Hai; Qin Meng; Cao Yi; Wang Wei

    2013-01-01

    There are large amounts of osmolytes inside cells, which impact many physiological processes by complicated mechanisms. The osmolyte effects on the stability and folding of proteins have been studied in detail using simple two-state folding proteins. However, many important functional proteins fold in complex pathways involving various intermediates. Little is known about the osmolyte effects on the folding and unfolding of these proteins. It is noted that β-lactoglobulin (BLG) is an example of such proteins, whose unfolding involves an obvious intermediate state. Using equilibrium chemical denaturation and stopped-flow kinetics, we investigate the unfolding of BLG in the presence of different osmolytes, e.g., glycerol, ethylene glycol (EG) and poly(ethylene glycol)400 (PEG400). It is found that all these osmolytes can stabilize the unfolding intermediate by modulating the relative unfolding kinetics of the native and the intermediate states. The stabilization effects are similar for EG and PEG400 but distinct for glycerol. Since the unfolding intermediates of many proteins are directly related to protein misfolding diseases, evaluation of the osmolyte effects for the unfolding of these proteins in vitro should be beneficial for the understanding of the occurrence of the related diseases in vivo

  16. Effects of Sunphenon and Polyphenon 60 on proteolytic pathways ...

    Indian Academy of Sciences (India)

    Moreover, Sunphenon may regulate the skeletal muscle genes/promote skeletal muscle recovery by the up-regulation of myogenin and MyoD and suppression of -calpain and inflammatory pathways and may regulate the apoptosis pathways. Our findings suggest that dietary supplementation of Sunphenon might reduce ...

  17. Effective communications bring greater public acceptance

    International Nuclear Information System (INIS)

    Clawson, C.

    1992-01-01

    In 1986, GPU Nuclear Corporation announced a plan to evaporate into the atmosphere 2.3 million gal of water remaining from the Three Mile Island Unit 2 (TMI-2) accident. The water would be processed to remove most of the radioactivity, but still remaining were >1,000 Ci of tritium to be released to the atmosphere during the evaporation process. It was expected that, following regulatory approvals, it would take >2 yr to complete the process. Fed by well-established antinuclear groups, public concern about evaporating the TMI-2-accident-generated water ran high among residents living near the plant. In the years since the TMI-2 accident, GPU Nuclear had developed a highly effective communications program in the communities surrounding TMI. This ongoing program provided a solid foundation on which to create and implement a risk communications approach to community understanding and acceptance of the evaporation process

  18. Directed Motivational Currents: Using vision to create effective motivational pathways

    Directory of Open Access Journals (Sweden)

    Christine Muir

    2013-10-01

    Full Text Available Vision, that is, the mental representation of the sensory experience of a future goal state (involving imagination and imagery, is currently at the forefront of motivational innovation, and in recent years it has been seen increasingly more often in the motivational tool kit of practicing language teachers. Theories such as Dörnyei’s L2 motivational self system have explored the power that creating effective visions can harness (see, e.g., Dörnyei & Kubanyiova, 2014 and when viewed in conjunction with other current research avenues, such as future time perspective and dynamic systems theory, vision offers exciting potential. A Directed Motivational Current is a new motivational construct that we suggest is capable of integrating many current theoretical strands with vision: It can be described as a motivational drive which energises long-term, sustained behaviour (such as language learning, and through placing vision and goals as critical central components within this construct, it offers real and practical motivational potential. In this conceptual paper, we first discuss current understandings of vision and of Directed Motivational Currents, and then analyse how they may be optimally integrated and employed to create effective motivational pathways in language learning environments.

  19. Finding pathways to more equitable and meaningful public-scientist partnerships

    Science.gov (United States)

    Daniela Soleri; Jonathan W. Long; Monica D. Ramirez-Andreotta; Ruth Eitemiller; Rajul Pandyaǁ

    2016-01-01

    For many, citizen science is exciting because of the possibility for more diverse, equitable partnerships in scientific research with outcomes considered meaningful and useful by all, including public participants. This was the focus of a symposium we organized at the 2015 conference of the Citizen Science Association. Here we synthesize points made by symposium...

  20. Bone Biomarkers on the Pathway to Effective Spaceflight Countermeasures

    Science.gov (United States)

    Spatz, Jordan

    2009-01-01

    Osteocyte cells are the most abundant yet least understood bone cell type in the human body. However, recent discovers in osteocyte cell biology have shed light on their importance as key mechanosensing cells regulating the bone remodeling process. Thus, we propose the first ever in vitro gene expression evaluation of osteocytes exposed to simulated microgravity to determine mechanistic pathways of their gravity sensing ability. Improved understanding of the fundamental mechanisms at the osteocyte cellular level may lead to improved treatment options to mitigate the effects of bone loss encountered by astronauts on long duration space missions and provide tailored treatment options for maintaining bone strength of immobilized/partially paralyzed patients here on Earth. Aim 1: Characterize the gene expression patterns and protein levels following exposure of murine osteocytelike cell line (MLO-Y4) to simulated microgravity using the NASA Rotating Wall Vessel (RWV) Bioreactor. Osteocytes are theorized to be the mechanosensors and transducers of mechanical load for bones, yet the biological mechanism of this action remains elusive. We propose to investigate the genetic regulation of the mechanism of the MLO-Y4 cell in the NASA Bioreactor as it is the accepted ground-based analog for simulating vector averaged microgravity.

  1. Patient engagement in healthcare: pathways for effective medical decision making

    Directory of Open Access Journals (Sweden)

    Serena Barello

    2015-04-01

    Full Text Available Making patients protagonists of decisions about their care is a primacy in the 21st century medical ethics. Precisely, to favor shared treatment decisions potentially enables patients’ autonomy and self-determination, and protects patients’ rights to make decisions about their own future care. To fully accomplish this goal, medicine should take into account the complexity of the healthcare decision making processes: patients may experience dilemmas when having to take decisions that not only concern their patient role/identity but also involve the psychosocial impact of treatments on their overall life quality. A deeper understanding of the patients’ expected role in the decision making process across their illness journey may favor the optimal implementation of this practice into the day-to-day medical agenda. In this paper, authors discuss the value of assuming the Patient Health Engagement Model to sustain successful pathways for effective medical decision making throughout the patient’s illness course. This model and its relational implication for the clinical encounter might be the base for an innovative “patient-doctor relational agenda” able to sustain an “engagement-sensitive” medical decision making.

  2. Ranking scientific publications: the effect of nonlinearity

    Science.gov (United States)

    Yao, Liyang; Wei, Tian; Zeng, An; Fan, Ying; di, Zengru

    2014-10-01

    Ranking the significance of scientific publications is a long-standing challenge. The network-based analysis is a natural and common approach for evaluating the scientific credit of papers. Although the number of citations has been widely used as a metric to rank papers, recently some iterative processes such as the well-known PageRank algorithm have been applied to the citation networks to address this problem. In this paper, we introduce nonlinearity to the PageRank algorithm when aggregating resources from different nodes to further enhance the effect of important papers. The validation of our method is performed on the data of American Physical Society (APS) journals. The results indicate that the nonlinearity improves the performance of the PageRank algorithm in terms of ranking effectiveness, as well as robustness against malicious manipulations. Although the nonlinearity analysis is based on the PageRank algorithm, it can be easily extended to other iterative ranking algorithms and similar improvements are expected.

  3. Ranking scientific publications: the effect of nonlinearity.

    Science.gov (United States)

    Yao, Liyang; Wei, Tian; Zeng, An; Fan, Ying; Di, Zengru

    2014-10-17

    Ranking the significance of scientific publications is a long-standing challenge. The network-based analysis is a natural and common approach for evaluating the scientific credit of papers. Although the number of citations has been widely used as a metric to rank papers, recently some iterative processes such as the well-known PageRank algorithm have been applied to the citation networks to address this problem. In this paper, we introduce nonlinearity to the PageRank algorithm when aggregating resources from different nodes to further enhance the effect of important papers. The validation of our method is performed on the data of American Physical Society (APS) journals. The results indicate that the nonlinearity improves the performance of the PageRank algorithm in terms of ranking effectiveness, as well as robustness against malicious manipulations. Although the nonlinearity analysis is based on the PageRank algorithm, it can be easily extended to other iterative ranking algorithms and similar improvements are expected.

  4. Effective public health management: The Nigerian experience | Abe ...

    African Journals Online (AJOL)

    Public health management in Nigeria is the process of mobilizing and deploying resources for the provision of effective public health services. To ensure an effective public health, population based strategies would need to be put in place and this would require proper management to yield desired results. This paper ...

  5. Private versus Public Feedback - The Incentive Effects of Symbolic Awards

    DEFF Research Database (Denmark)

    Gerhards, Leonie; Siemer, Neele

    We experimentally compare the incentive effects of rewarding individuals for outstanding performance publicly versus privately. We implement two real-effort tasks, which differ in how prestigious subjects perceive working on them. In both tasks private and public feedback similarly enhances...... experiment at a secondary school we furthermore compare the incentive effects of different forms of public recognition....

  6. A study on improving the regulatory effectiveness and public participation

    International Nuclear Information System (INIS)

    Choi, B. S.; Choi, Y. G.; Cho, B. H.; Lee, H. W.

    2006-02-01

    The scope of this study is : review the theories about public participation in nuclear safety regulation, we develop an understanding of the concept and compare the effectiveness of different approaches to public participation. Reviews the cases of public participation in foreign countries and searches for important implications. To examine the current measures of public participation in nuclear safety regulatory process and to evaluate the present demand of the public including residents nearby nuclear facilities. Based upon the discussions on the above topics, examines prerequisites for success of public participation and presents alternatives of public participation in the concrete

  7. Policy alienation of public professionals: the effects

    NARCIS (Netherlands)

    L.G. Tummers (Lars)

    2008-01-01

    textabstractNowadays, many public professionals face identification problems towards public policies they have to implement; that is, they experience policy alienation. We conceptualize policy alienation, starting from the sociological concept of alienation and showing how this can be used in the

  8. Reputation Effects in Public and Private Interactions

    Science.gov (United States)

    Ohtsuki, Hisashi; Iwasa, Yoh; Nowak, Martin A.

    2015-01-01

    We study the evolution of cooperation in a model of indirect reciprocity where people interact in public and private situations. Public interactions have a high chance to be observed by others and always affect reputation. Private interactions have a lower chance to be observed and only occasionally affect reputation. We explore all second order social norms and study conditions for evolutionary stability of action rules. We observe the competition between “honest” and “hypocritical” strategies. The former cooperate both in public and in private. The later cooperate in public, where many others are watching, but try to get away with defection in private situations. The hypocritical idea is that in private situations it does not pay-off to cooperate, because there is a good chance that nobody will notice it. We find simple and intuitive conditions for the evolution of honest strategies. PMID:26606239

  9. Health effects from swimming training in chlorinated pools and the corresponding metabolic stress pathways.

    Directory of Open Access Journals (Sweden)

    Jiang-Hua Li

    Full Text Available Chlorination is the most popular method for disinfecting swimming pool water; however, although pathogens are being killed, many toxic compounds, called disinfection by-products (DBPs, are formed. Numerous epidemiological publications have associated the chlorination of pools with dysfunctions of the respiratory system and with some other diseases. However, the findings concerning these associations are not always consistent and have not been confirmed by toxicological studies. Therefore, the health effects from swimming in chlorinated pools and the corresponding stress reactions in organisms are unclear. In this study, we show that although the growth and behaviors of experimental rats were not affected, their health, training effects and metabolic profiles were significantly affected by a 12-week swimming training program in chlorinated water identical to that of public pools. Interestingly, the eyes and skin are the organs that are more directly affected than the lungs by the irritants in chlorinated water; instead of chlorination, training intensity, training frequency and choking on water may be the primary factors for lung damage induced by swimming. Among the five major organs (the heart, liver, spleen, lungs and kidneys, the liver is the most likely target of DBPs. Through metabolomics analysis, the corresponding metabolic stress pathways and a defensive system focusing on taurine were presented, based on which the corresponding countermeasures can be developed for swimming athletes and for others who spend a lot of time in chlorinated swimming pools.

  10. The effect of chronic seaweed subsidies on herbivory: plant-mediated fertilization pathway overshadows lizard-mediated predator pathways.

    Science.gov (United States)

    Piovia-Scott, Jonah; Spiller, David A; Takimoto, Gaku; Yang, Louie H; Wright, Amber N; Schoener, Thomas W

    2013-08-01

    Flows of energy and materials link ecosystems worldwide and have important consequences for the structure of ecological communities. While these resource subsidies typically enter recipient food webs through multiple channels, most previous studies focussed on a single pathway of resource input. We used path analysis to evaluate multiple pathways connecting chronic marine resource inputs (in the form of seaweed deposits) and herbivory in a shoreline terrestrial ecosystem. We found statistical support for a fertilization effect (seaweed increased foliar nitrogen content, leading to greater herbivory) and a lizard numerical response effect (seaweed increased lizard densities, leading to reduced herbivory), but not for a lizard diet-shift effect (seaweed increased the proportion of marine-derived prey in lizard diets, but lizard diet was not strongly associated with herbivory). Greater seaweed abundance was associated with greater herbivory, and the fertilization effect was larger than the combined lizard effects. Thus, the bottom-up, plant-mediated effect of fertilization on herbivory overshadowed the top-down effects of lizard predators. These results, from unmanipulated shoreline plots with persistent differences in chronic seaweed deposition, differ from those of a previous experimental study of the short-term effects of a pulse of seaweed deposition: while the increase in herbivory in response to chronic seaweed deposition was due to the fertilization effect, the short-term increase in herbivory in response to a pulse of seaweed deposition was due to the lizard diet-shift effect. This contrast highlights the importance of the temporal pattern of resource inputs in determining the mechanism of community response to resource subsidies.

  11. Development of computationally predicted Adverse Outcome Pathway (AOP) networks through data mining and integration of publicly available in vivo, in vitro, phenotype, and biological pathway data

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  12. Generation of computationally predicted Adverse Outcome Pathway networks through integration of publicly available in vivo, in vitro, phenotype, and biological pathway data.

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is becoming a widely used tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse ecological and human health outcomes. However, the conventional process...

  13. The public and effective risk communication

    NARCIS (Netherlands)

    Frewer, L.J.

    2004-01-01

    Abstract Public perceptions of risk have often been dismissed on the basis of ¿irrationality¿, and have tended to be excluded from policy processes by risk assessors and managers. People¿s responses to different risks are determined by psychological factors. The technical risk estimates

  14. Public policy: effective treatment for tobacco disease.

    Science.gov (United States)

    Scheg, K E

    1996-01-01

    Public policy initiatives offer greater promise than other strategies for reducing the major public health problem of death and disease due to smoking. Three of the most critical public policy areas today are smoke-free environments, youth access, and advertising. While earlier laws separated smokers and nonsmokers into separate sections, the focus now is on smoke-free environments. Various places, however, most notably restaurants, often remain polluted with tobacco smoke and put women at heightened risk of disease and death. Restricting youth access to tobacco products has also gained momentum in the 1990s. The recently proposed Food and Drug Administration regulations designed to reduce smoking by minors by 50% over seven years are the most significant national public policy initiatives ever to address the problem of children smoking. Measures to counter the tobacco industry's massive advertising and promotion campaigns have also increased. The federal government has begun enforcing the prohibition on cigarette advertising on television, and local jurisdictions have restricted tobacco billboards and point-of-sale advertising.

  15. Decreasing medical complications for total knee arthroplasty: Effect of Critical Pathways on Outcomes

    Directory of Open Access Journals (Sweden)

    Solomon Daniel H

    2010-07-01

    Full Text Available Abstract Background Studies on critical pathway use have demonstrated decreased length of stay and cost without compromise in quality of care. However, pathway effectiveness is difficult to determine given methodological flaws, such as small or single center cohorts. We studied the effect of critical pathways on total knee replacement outcomes in a large population-based study. Methods We identified hospitals in four US states that performed total knee replacements. We sent a questionnaire to surgical administrators in these hospitals including items about critical pathway use and hospital characteristics potentially related to outcomes. Patient data were obtained from Medicare claims, including demographics, comorbidities, 90-day postoperative complications and length of hospital stay. The principal outcome measure was the risk of having one or more postoperative complications. Results Two hundred ninety five hospitals (73% responded to the questionnaire, with 201 reporting the use of critical pathways. 9,157 Medicare beneficiaries underwent TKR in these hospitals with a mean age of 74 years (± 5.8. After adjusting for both patient and hospital related variables, patients in hospitals with pathways were 32% less likely to have a postoperative complication compared to patients in hospitals without pathways (OR 0.68, 95% CI 0.50-0.92. Patients managed on a critical pathway had an average length of stay 0.5 days (95% CI 0.3-0.6 shorter than patients not managed on a pathway. Conclusion Medicare patients undergoing total knee replacement surgery in hospitals that used critical pathways had fewer postoperative complications than patients in hospitals without pathways, even after adjusting for patient and hospital related factors. This study has helped to establish that critical pathway use is associated with lower rates of postoperative mortality and complications following total knee replacement after adjusting for measured variables.

  16. Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.

    Directory of Open Access Journals (Sweden)

    Jian Li

    Full Text Available To date, it is widely recognized that Non-Steroidal Anti-Inflammatory Drugs (NSAIDs can exert considerable anti-tumor effects regarding many types of cancers. The prolonged use of NSAIDs is highly associated with diverse side effects. Therefore, tailoring down the NSAID application onto individual patients has become a necessary and relevant step towards personalized medicine. This study conducts the systemsbiological approach to construct a molecular model (NSAID model containing a cyclooxygenase (COX-pathway and its related signaling pathways. Four cancer hallmarks are integrated into the model to reflect different developmental aspects of tumorigenesis. In addition, a Flux-Comparative-Analysis (FCA based on Petri net is developed to transfer the dynamic properties (including drug responsiveness of individual cellular system into the model. The gene expression profiles of different tumor-types with available drug-response information are applied to validate the predictive ability of the NSAID model. Moreover, two therapeutic developmental strategies, synthetic lethality and microRNA (miRNA biomarker discovery, are investigated based on the COX-pathway. In conclusion, the result of this study demonstrates that the NSAID model involving gene expression, gene regulation, signal transduction, protein interaction and other cellular processes, is able to predict the individual cellular responses for different therapeutic interventions (such as NS-398 and COX-2 specific siRNA inhibition. This strongly indicates that this type of model is able to reflect the physiological, developmental and pathological processes of an individual. The approach of miRNA biomarker discovery is demonstrated for identifying miRNAs with oncogenic and tumor suppressive functions for individual cell lines of breast-, colon- and lung-tumor. The achieved results are in line with different independent studies that investigated miRNA biomarker related to diagnostics of cancer

  17. MODELLING OF FINANCIAL EFFECTIVENESS AND COMPARATIVE ANALYSIS OF PUBLIC-PRIVATE PARTNERSHIP PROJECTS AND PUBLIC PROCUREMENT

    Directory of Open Access Journals (Sweden)

    Kuznetsov Aleksey Alekseevich

    2017-10-01

    Full Text Available The article substantiates the necessity of extension and development of tools for methodological evaluation of effectiveness of public-private partnership (PPP projects both individually and in comparison of effectiveness of various mechanisms of projects realization on the example of traditional public procurement. The author proposed an original technique of modelling cash flows of private and public partners when realizing the projects based on PPP and on public procurement. The model enables us promptly and with sufficient accuracy to reveal comparative advantages of project forms of PPP and public procurement, and also assess financial effectiveness of the PPP projects for each partner. The modelling is relatively straightforward and reliable. The model also enables us to evaluate public partner's expenses for availability, find the terms and thresholds for interest rates of financing attracted by the partners and for risk probabilities to ensure comparative advantage of PPP project. Proposed criteria of effectiveness are compared with methodological recommendations provided by the Ministry of Economic Development of the Russian Federation. Subject: public and private organizations, financial institutions, development institutions and their theoretical and practical techniques for effectiveness evaluation of public-private partnership (PPP projects. Complexity of effectiveness evaluation and the lack of unified and accepted methodology are among the factors that limit the development of PPP in the Russian Federation nowadays. Research objectives: development of methodological methods for assessing financial efficiency of PPP projects by creating and justifying application of new principles and methods of modelling, and also criteria for effectiveness of PPP projects both individually and in comparison with the public procurement. Materials and methods: open database of ongoing PPP projects in the Russian Federation and abroad was used. The

  18. Assessing the Effect of China's National Publicity Films from the Perspective of Public Diplomacy

    Directory of Open Access Journals (Sweden)

    Cao Wei

    2015-12-01

    Full Text Available This article empirically assessed the effect of China’s national publicity film launched in Times Square in Manhattan, New York. To this end, the author gave a set of general criteria and indicators to measure the effect of national publicity films. Whether the publicity film was effective depends on whether American people’s image perceptions of China were improved after it was launched. Quantitative indicators are: the number of reports in the target country and the predispositions of the reports; the target country people’s participation and their predispositions; and the real behavior of the target country people. The analysis revealed that the 2011 national publicity film did not achieve the anticipated effect. The number of U.S. mainstream media reports was less than expected and their evaluations were quite negative; the participation of American people was low and the extent of the favorability both of the publicity film and China was not high; and the launch of the publicity film did not trigger a travel boom to China. Accordingly, this article suggested that the future implementation of China’s national publicity films focuses on two aspects: first, pay attention to cultural differences and enhance the comprehensibility of the discourse; second, practice what it preaches and strengthen the credibility of the discourse.

  19. To what extent can the nuclear public relations be effective?

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, Teruaki [CRC Research Institute, Tokyo (Japan)

    1996-06-01

    The effect of public relations (PRs) on the public`s attitude to nuclear energy was assessed using a model developed under the assumption that the extent of attitude change of the public by the PRs activity is essentially the same as that by the nuclear information released by the newsmedia. The attitude change of the public was quantitatively estimated by setting variables explicitly manifesting the activities such as the circulation of exclusive publicity and the area of advertising messages in the newspaper as parameters. The public`s attitude became clear to have a nonlinear dependence on the amount of activity, the extent of its change being varied considerably with demographic classes. Under a given financial condition, the offer of PRs information to the people, as many as possible in a target region, in spite of its little force of appeal, was found to be more effective for the amelioration of public attitude than the repeated offer of the information to a limited member of the public. It also became clear that there exists the most effective media mix for the activity depending on the extent of target region and on the target class of demography, therefore, it is quite significant to determine beforehand the proper conditions for the activity to be executed, such a situation indicating the need for the introduction of nuclear PRs management. (Author).

  20. Effective radiological communications with the public

    International Nuclear Information System (INIS)

    Jones, C.G.; Roessler, G.S.; Brent, R.L.

    2004-01-01

    About the Health Physics Society. The Health Physics Society (HPS) is a professional organization whose mission is excellence in the science and practice of radiation safety. Since its formation in 1956, the Society has grown to approximately 6,000 scientists, physicians, engineers, lawyers, and other professionals representing academia, industry, government, national laboratories, and other organizations. Society activities include encouraging research in radiation science, developing standards, and disseminating radiation safety information. Society members are involved in understanding, evaluating, and controlling the potential risks from radiation relative to the benefits. Although the Society already was publishing the Health Physics Journal and Newsletter, in 1996, as part of furthering the HPS mission of information communication and radiological protection education, an HPS Web site was created at www.hps.org to disseminate information on the Society's activities, objectives, membership, news and events, publications, education, and public information. In September 2001, Web structure for the site was further developed and refined, and it was during this development phase that the concept of the ask the experts (ATE) feature was born. (orig.)

  1. Effective radiological communications with the public

    Energy Technology Data Exchange (ETDEWEB)

    Jones, C.G. [US Nuclear Regulatory Commission, Washington, DC (United States); Roessler, G.S. [Healthy Physics Society, Elysian, MN (United States); Brent, R.L. [Alfred I. duPont Hospital for Children, Environmental and Clinical Teratology Lab., Wilmington, DE (United States)

    2004-07-01

    About the Health Physics Society. The Health Physics Society (HPS) is a professional organization whose mission is excellence in the science and practice of radiation safety. Since its formation in 1956, the Society has grown to approximately 6,000 scientists, physicians, engineers, lawyers, and other professionals representing academia, industry, government, national laboratories, and other organizations. Society activities include encouraging research in radiation science, developing standards, and disseminating radiation safety information. Society members are involved in understanding, evaluating, and controlling the potential risks from radiation relative to the benefits. Although the Society already was publishing the Health Physics Journal and Newsletter, in 1996, as part of furthering the HPS mission of information communication and radiological protection education, an HPS Web site was created at www.hps.org to disseminate information on the Society's activities, objectives, membership, news and events, publications, education, and public information. In September 2001, Web structure for the site was further developed and refined, and it was during this development phase that the concept of the ask the experts (ATE) feature was born. (orig.)

  2. New public diplomacy and its effects on international level

    OpenAIRE

    Elena Gurgu; Aristide Dumitru Cociuban

    2016-01-01

    Abstract. The purpose of this article is to make known the new type of public diplomacy and the effects this new diplomacy can have internationally. The objectives of our article refer to the context of change, the role of the media in public diplomacy, new approaches and elements of public diplomacy, current diplomacy in scientific and technical way and the use of scientific cooperation to improve bilateral relations between countries.

  3. New public diplomacy and its effects on international level

    Directory of Open Access Journals (Sweden)

    Elena Gurgu

    2016-09-01

    Full Text Available Abstract. The purpose of this article is to make known the new type of public diplomacy and the effects this new diplomacy can have internationally. The objectives of our article refer to the context of change, the role of the media in public diplomacy, new approaches and elements of public diplomacy, current diplomacy in scientific and technical way and the use of scientific cooperation to improve bilateral relations between countries.

  4. The effective use of fluorides in public health

    DEFF Research Database (Denmark)

    Jones, Sheila; Burt, Brian A; Petersen, Poul Erik

    2005-01-01

    , systematic reviews summarizing these extensive databases have indicated that water fluoridation and fluoride toothpastes both substantially reduce the prevalence and incidence of dental caries. We present four case studies that illustrate the use of fluoride in modern public health practice, focusing on......Dental caries remain a public health problem for many developing countries and for underprivileged populations in developed countries. This paper outlines the historical development of public health approaches to the use of fluoride and comments on their effectiveness. Early research...

  5. Development of a pluripotent stem cell derived neuronal model to identify chemically induced pathway perturbations in relation to neurotoxicity: Effects of CREB pathway inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Pistollato, Francesca; Louisse, Jochem; Scelfo, Bibiana; Mennecozzi, Milena [Institute for Health and Consumer Protection (IHCP), JRC, Ispra (Italy); Accordi, Benedetta; Basso, Giuseppe [Oncohematology Laboratory, Department of Woman and Child Health, University of Padova, Padova (Italy); Gaspar, John Antonydas [Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Cologne (Germany); Zagoura, Dimitra; Barilari, Manuela; Palosaari, Taina [Institute for Health and Consumer Protection (IHCP), JRC, Ispra (Italy); Sachinidis, Agapios [Center of Physiology and Pathophysiology, Institute of Neurophysiology, University of Cologne, Cologne (Germany); Bremer-Hoffmann, Susanne, E-mail: susanne.bremer@jrc.ec.europa.eu [Institute for Health and Consumer Protection (IHCP), JRC, Ispra (Italy)

    2014-10-15

    According to the advocated paradigm shift in toxicology, acquisition of knowledge on the mechanisms underlying the toxicity of chemicals, such as perturbations of biological pathways, is of primary interest. Pluripotent stem cells (PSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), offer a unique opportunity to derive physiologically relevant human cell types to measure molecular and cellular effects of such pathway modulations. Here we compared the neuronal differentiation propensity of hESCs and hiPSCs with the aim to develop novel hiPSC-based tools for measuring pathway perturbation in relation to molecular and cellular effects in vitro. Among other fundamental pathways, also, the cAMP responsive element binding protein (CREB) pathway was activated in our neuronal models and gave us the opportunity to study time-dependent effects elicited by chemical perturbations of the CREB pathway in relation to cellular effects. We show that the inhibition of the CREB pathway, using 2-naphthol-AS-E-phosphate (KG-501), induced an inhibition of neurite outgrowth and synaptogenesis, as well as a decrease of MAP2{sup +} neuronal cells. These data indicate that a CREB pathway inhibition can be related to molecular and cellular effects that may be relevant for neurotoxicity testing, and, thus, qualify the use of our hiPSC-derived neuronal model for studying chemical-induced neurotoxicity resulting from pathway perturbations. - Highlights: • HESCs derived neuronal cells serve as benchmark for iPSC based neuronal toxicity test development. • Comparisons between hESCs and hiPSCs demonstrated variability of the epigenetic state • CREB pathway modulation have been explored in relation to the neurotoxicant exposure KG-501 • hiPSC might be promising tools to translate theoretical AoPs into toxicological in vitro tests.

  6. Job Performance Effectiveness: A Comparison of Teachers in Public ...

    African Journals Online (AJOL)

    Job Performance Effectiveness: A Comparison of Teachers in Public and Private Schools ... Teachers in the two types of schools were about the same in classroom ... Also that public school teachers must be provided with conducive teaching/learning environment to enable them meet up the ... AJOL African Journals Online.

  7. Public education on sources and effects of radioactive waste disposal

    International Nuclear Information System (INIS)

    Martin, J.E.; Rengan, K.

    1993-01-01

    A six-day workshop, developed for providing information on sources and effects of radioactive waste disposal to the general public, is described. The materials were used successfully with a group representing the general public. An extension of the workshop for high school and junior high school science teachers is discussed. (author) 1 tab

  8. Effectively selling astronomy to the public -- fusing lessons learned from education, entertainment, advertising and public relations

    Science.gov (United States)

    Pallone, Arthur; Day, Jacque

    2010-03-01

    A great celestial story is only as effective as the teller of the tale. With passion and knowledge at the helm, we must search for ways to pass on enthusiasm to others while conveying sound science. Based on our experiences, we present an integrated approach -- one that borrows elements from education, entertainment, advertising, and public relations -- to choose an event, hook and keep the public's attention while making them want more, and provide some tips for increasing media presence.

  9. Measuring the effect of Sustainable Public Procurement

    NARCIS (Netherlands)

    Zijp MC; Kok L; Valk E de; DMG; M&V; M&V

    2018-01-01

    Many purchasing services of the Dutch local and central governments, aim to include the effects of products and services on human health and the environment in the procurement process. Sustainable procurement (SP) encompasses more than just price and quality considerations. SP can result, for

  10. Greenhouse effect economic simulation and public decision

    International Nuclear Information System (INIS)

    Giraud, P.N.

    2002-03-01

    As the other countries, engaged in the greenhouse effect fight, the France has to evaluate the greenhouse gases emissions and the corrective actions. Meanwhile the today models are not enough impressive. The economic tools authorize today a better evaluation. The technical working Group, presided by Pierre-Noel Giraud, proposes to use them largely and provides four main recommendations. (A.L.B.)

  11. To what extent can the nuclear public relations be effective?

    International Nuclear Information System (INIS)

    Ohnishi, Teruaki

    1996-01-01

    The effect of public relations (PRs) on the public's attitude to nuclear energy was assessed using a model developed under the assumption that the extent of attitude change of the public by the PRs activity is essentially the same as that by the nuclear information released by the newsmedia. The attitude change of the public was quantitatively estimated by setting variables explicitly manifesting the activities such as the circulation of exclusive publicity and the area of advertising messages in the newspaper as parameters. The public's attitude became clear to have a nonlinear dependence on the amount of activity, the extent of its change being varied considerably with demographic classes. Under a given financial condition, the offer of PRs information to the people, as many as possible in a target region, in spite of its little force of appeal, was found to be more effective for the amelioration of public attitude than the repeated offer of the information to a limited member of the public. It also became clear that there exists the most effective media mix for the activity depending on the extent of target region and on the target class of demography, therefore, it is quite significant to determine beforehand the proper conditions for the activity to be executed, such a situation indicating the need for the introduction of nuclear PRs management. (Author)

  12. Effect of the depreciation of public goods in spatial public goods games

    Science.gov (United States)

    Shi, Dong-Mei; Zhuang, Yong; Wang, Bing-Hong

    2012-02-01

    In this work, the depreciation effect of public goods is considered in the public goods games, which is realized by rescaling the multiplication factor r of each group as r‧=r( (β≥0). It is assumed that each individual enjoys the full profit r of the public goods if all the players of this group are cooperators. Otherwise, the value of public goods is reduced to r‧. It is found that compared with the original version (β=0), the emergence of cooperation is remarkably promoted for β>0, and there exist intermediate values of β inducing the best cooperation. Particularly, there exists a range of β inducing the highest cooperative level, and this range of β broadens as r increases. It is further presented that the variation of cooperator density with noise has close relations with the values of β and r, and cooperation at an intermediate value of β=1.0 is most tolerant to noise.

  13. Effect of curcumin on aged Drosophila melanogaster: a pathway prediction analysis.

    Science.gov (United States)

    Zhang, Zhi-guo; Niu, Xu-yan; Lu, Ai-ping; Xiao, Gary Guishan

    2015-02-01

    To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis. A total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Genes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

  14. Effects of clinical pathways in the joint replacement: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Faggiano F

    2009-07-01

    Full Text Available Abstract Background A meta-analysis was performed to evaluate the use of clinical pathways for hip and knee joint replacements when compared with standard medical care. The impact of clinical pathways was evaluated assessing the major outcomes of in-hospital hip and knee joint replacement processes: postoperative complications, number of patients discharged at home, length of in-hospital stay and direct costs. Methods Medline, Cinahl, Embase and the Cochrane Central Register of Controlled Trials were searched. The search was performed from 1975 to 2007. Each study was assessed independently by two reviewers. The assessment of methodological quality of the included studies was based on the Jadad methodological approach and on the New Castle Ottawa Scale. Data analysis abided by the guidelines set out by The Cochrane Collaboration regarding statistical methods. Meta-analyses were performed using RevMan software, version 4.2. Results Twenty-two studies met the study inclusion criteria and were included in the meta-analysis for a total sample of 6,316 patients. The aggregate overall results showed significantly fewer patients suffering postoperative complications in the clinical pathways group when compared with the standard care group. A shorter length of stay in the clinical pathway group was also observed and lower costs during hospital stay were associated with the use of the clinical pathways. No significant differences were found in the rates of discharge to home. Conclusion The results of this meta-analysis show that clinical pathways can significantly improve the quality of care even if it is not possible to conclude that the implementation of clinical pathways is a cost-effective process, because none of the included studies analysed the cost of the development and implementation of the pathways. Based on the results we assume that pathways have impact on the organisation of care if the care process is structured in a standardised way

  15. The investigation of substituent effects on the fragmentation pathways of pentacoordinated phenoxyspirophosphoranes by ESI-MSn.

    Science.gov (United States)

    Cui, Xiaoyan; Sun, Can; Zhao, Pei; Wang, Yanyan; Guo, Yanchun; Zhao, Yufen; Cao, Shuxia

    2018-04-01

    The fragmentation pathways of pentacoordinated phenoxyspirophosphoranes were investigated in the positive mode by electrospray ionization multistage mass spectrometry. The results demonstrate that the sodium adducts of the title compounds undergo two competitive fragmentation pathways, and the fragmentation patterns are heavily dependent on the various substituent patterns at the phenolic group. An electron-withdrawing substituent at the ortho-position always results in the removal of a corresponding phenol analogue, while cleavage by spiroring opening becomes the predominant fragmentation pathway if an electron-donating substituent is at the phenolic group. The substituent effects on the competitive fragmentation pathways were further elucidated by theoretical calculations, single crystal structure analysis, and high-resolution mass spectrometry. The results contribute to the understanding of the gas-phase fragmentation reactions and the structure identification of spirophosphorane analogues by electrospray ionization multistage mass spectrometry. Copyright © 2018 John Wiley & Sons, Ltd.

  16. Publicity.

    Science.gov (United States)

    Chisholm, Joan

    Publicity for preschool cooperatives is described. Publicity helps produce financial support for preschool cooperatives. It may take the form of posters, brochures, newsletters, open house, newspaper coverage, and radio and television. Word of mouth and general good will in the community are the best avenues of publicity that a cooperative nursery…

  17. Research on Effective Supply Mode of Rural Public Goods

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    On the basis of definition and classification of rural public goods, this paper analyses the status quo of public goods supply in vast rural areas of China, and it indicates that the electricity and communication facility in rural areas have not yet been popularized; the culture and education facility is critically backward; the medical care and social warfare institutions are short. It points out the rational supply model of public goods as follows: the government plays dominant role in the public goods supply with a large amount of investments, related to the quality of living and production of multitudinous farmers; small wieldy quasi-public goods that can be easily supplied and marginalized public goods can introduce multiplex supply main body under the framework of government guidance. According to this model, corresponding policy suggestions are put forward as follows: increase financial inputs, and perfect local financial system; actively encourage the majority of farmers in rural areas to participate in public goods supply mechanism, so that the supply has pertinence; vigorously develop multiplex supply system of rural public goods, to ensure effective supply.

  18. Directed Motivational Currents: Using vision to create effective motivational pathways

    OpenAIRE

    Christine Muir; Zoltán Dörnyei

    2013-01-01

    Vision, that is, the mental representation of the sensory experience of a future goal state (involving imagination and imagery), is currently at the forefront of motivational innovation, and in recent years it has been seen increasingly more often in the motivational tool kit of practicing language teachers. Theories such as Dörnyei’s L2 motivational self system have explored the power that creating effective visions can harness (see, e.g., Dörnyei & Kubanyiova, 2014) and when viewed in conju...

  19. Error framing effects on performance: cognitive, motivational, and affective pathways.

    Science.gov (United States)

    Steele-Johnson, Debra; Kalinoski, Zachary T

    2014-01-01

    Our purpose was to examine whether positive error framing, that is, making errors salient and cuing individuals to see errors as useful, can benefit learning when task exploration is constrained. Recent research has demonstrated the benefits of a newer approach to training, that is, error management training, that includes the opportunity to actively explore the task and framing errors as beneficial to learning complex tasks (Keith & Frese, 2008). Other research has highlighted the important role of errors in on-the-job learning in complex domains (Hutchins, 1995). Participants (N = 168) from a large undergraduate university performed a class scheduling task. Results provided support for a hypothesized path model in which error framing influenced cognitive, motivational, and affective factors which in turn differentially affected performance quantity and quality. Within this model, error framing had significant direct effects on metacognition and self-efficacy. Our results suggest that positive error framing can have beneficial effects even when tasks cannot be structured to support extensive exploration. Whereas future research can expand our understanding of error framing effects on outcomes, results from the current study suggest that positive error framing can facilitate learning from errors in real-time performance of tasks.

  20. Improving the effectiveness of public entities procurement practices

    OpenAIRE

    2013-01-01

    M. Com. (Business Management) The media and the Auditor General have extensively reported on the ineffective and unethical conduct of public sector employees regarding the procurement of goods and services. The Auditor General’s report demonstrates that there is evidence that public sector procurement processes are less than adequate to achieve constitutional procurement goals, which are to conduct processes that are fair, equitable, transparent, competitive and cost-effective The delivery...

  1. Mercury as a Global Pollutant: Sources, Pathways, and Effects

    Science.gov (United States)

    2013-01-01

    Mercury (Hg) is a global pollutant that affects human and ecosystem health. We synthesize understanding of sources, atmosphere-land-ocean Hg dynamics and health effects, and consider the implications of Hg-control policies. Primary anthropogenic Hg emissions greatly exceed natural geogenic sources, resulting in increases in Hg reservoirs and subsequent secondary Hg emissions that facilitate its global distribution. The ultimate fate of emitted Hg is primarily recalcitrant soil pools and deep ocean waters and sediments. Transfers of Hg emissions to largely unavailable reservoirs occur over the time scale of centuries, and are primarily mediated through atmospheric exchanges of wet/dry deposition and evasion from vegetation, soil organic matter and ocean surfaces. A key link between inorganic Hg inputs and exposure of humans and wildlife is the net production of methylmercury, which occurs mainly in reducing zones in freshwater, terrestrial, and coastal environments, and the subsurface ocean. Elevated human exposure to methylmercury primarily results from consumption of estuarine and marine fish. Developing fetuses are most at risk from this neurotoxin but health effects of highly exposed populations and wildlife are also a concern. Integration of Hg science with national and international policy efforts is needed to target efforts and evaluate efficacy. PMID:23590191

  2. School-Based Management and Effectiveness of Public Secondary ...

    African Journals Online (AJOL)

    ... to achieve its statutory roles, objectives and aspirations. We suggest that the adoption of School-based management by way of increasing the principals' sphere of influence would facilitate effective service delivery in schools. Keywords: school-based management, principals' effectiveness, public secondary schools.

  3. Effect of demographic variables on public attitudes towards ...

    African Journals Online (AJOL)

    In conclusion, background variables do have a significant effect on some of the dimensions of Malaysians' attitudes towards modern biotechnology. The research findings will be useful for understanding the effect of background variables on public attitudes towards the application of gene technology in medicine.

  4. Evaluating the effect of clinical care pathways on quality of cancer care: analysis of breast, colon and rectal cancer pathways.

    Science.gov (United States)

    Bao, Han; Yang, Fengjuan; Su, Shaofei; Wang, Xinyu; Zhang, Meiqi; Xiao, Yaming; Jiang, Hao; Wang, Jiaying; Liu, Meina

    2016-05-01

    Substantial gaps exist between clinical practice and evidence-based cancer care, potentially leading to adverse clinical outcomes and decreased quality of life for cancer patients. This study aimed to evaluate the usefulness of clinical pathways as a tool for improving quality of cancer care, using breast, colon, and rectal cancer pathways as demonstrations. Newly diagnosed patients with invasive breast, colon, and rectal cancer were enrolled as pre-pathway groups, while patients with the same diagnoses treated according to clinical pathways were recruited for post-pathway groups. Compliance with preoperative core biopsy or fine-needle aspiration, utilization of sentinel lymph node biopsy, and proportion of patients whose tumor hormone receptor status was stated in pathology report were significantly increased after implementation of clinical pathway for breast cancer. For colon cancer, compliance with two care processes was significantly improved: surgical resection with anastomosis and resection of at least 12 lymph nodes. Regarding rectal cancer, there was a significant increase in compliance with preoperative evaluation of depth of tumor invasion, total mesorectal excision treatment of middle- or low-position rectal cancer, and proportion of patients who had undergone rectal cancer surgery whose pathology report included margin status. Moreover, total length of hospital stay was decreased remarkably for all three cancer types, and postoperative complications remained unchanged following implementation of the clinical pathways. Clinical pathways can improve compliance with standard care by implementing evidence-based quality indicators in daily practice, which could serve as a useful tool for narrowing the gap between clinical practice and evidence-based care.

  5. Effectively incorporating selected multimedia content into medical publications.

    Science.gov (United States)

    Ziegler, Alexander; Mietchen, Daniel; Faber, Cornelius; von Hausen, Wolfram; Schöbel, Christoph; Sellerer, Markus; Ziegler, Andreas

    2011-02-17

    Until fairly recently, medical publications have been handicapped by being restricted to non-electronic formats, effectively preventing the dissemination of complex audiovisual and three-dimensional data. However, authors and readers could significantly profit from advances in electronic publishing that permit the inclusion of multimedia content directly into an article. For the first time, the de facto gold standard for scientific publishing, the portable document format (PDF), is used here as a platform to embed a video and an audio sequence of patient data into a publication. Fully interactive three-dimensional models of a face and a schematic representation of a human brain are also part of this publication. We discuss the potential of this approach and its impact on the communication of scientific medical data, particularly with regard to electronic and open access publications. Finally, we emphasise how medical teaching can benefit from this new tool and comment on the future of medical publishing.

  6. Live-cell microscopy reveals small molecule inhibitor effects on MAPK pathway dynamics.

    Directory of Open Access Journals (Sweden)

    Daniel J Anderson

    Full Text Available Oncogenic mutations in the mitogen activated protein kinase (MAPK pathway are prevalent in human tumors, making this pathway a target of drug development efforts. Recently, ATP-competitive Raf inhibitors were shown to cause MAPK pathway activation via Raf kinase priming in wild-type BRaf cells and tumors, highlighting the need for a thorough understanding of signaling in the context of small molecule kinase inhibitors. Here, we present critical improvements in cell-line engineering and image analysis coupled with automated image acquisition that allow for the simultaneous identification of cellular localization of multiple MAPK pathway components (KRas, CRaf, Mek1 and Erk2. We use these assays in a systematic study of the effect of small molecule inhibitors across the MAPK cascade either as single agents or in combination. Both Raf inhibitor priming as well as the release from negative feedback induced by Mek and Erk inhibitors cause translocation of CRaf to the plasma membrane via mechanisms that are additive in pathway activation. Analysis of Erk activation and sub-cellular localization upon inhibitor treatments reveals differential inhibition and activation with the Raf inhibitors AZD628 and GDC0879 respectively. Since both single agent and combination studies of Raf and Mek inhibitors are currently in the clinic, our assays provide valuable insight into their effects on MAPK signaling in live cells.

  7. A comment on framing effects in linear public good games

    OpenAIRE

    Cartwright, Edward

    2016-01-01

    A number of recent papers have looked at framing effects in linear public good games. In this comment, I argue that, within this literature, the distinction between give-take and positive–negative framing effects has become blurred, and that this is a barrier towards understanding the experimental evidence on framing effects. To make these points, I first illustrate that frames can differ along both an externality and choice dimension. I then argue that the existing evidence is consistent wit...

  8. From recovery-oriented care to public health: Case studies of participatory public art as a pathway to wellness for persons with behavioral health challenges.

    Science.gov (United States)

    Mohatt, Nathaniel Vincent; Hunter, Bronwyn A; Matlin, Samantha L; Golden, Jane; Evans, Arthur C; Tebes, Jacob Kraemer

    2015-06-01

    The objective of this study is to identify individual mechanisms of change that result from engaging in an innovative participatory public art project for persons with significant behavioral health challenges. We present two case studies that examine how participatory public art promotes recovery and wellness. This research is part of a larger, multilevel comparative outcome trial on the impact of participatory public art on the health and well-being of adults in recovery from mental illness and addiction and on the distressed city neighborhoods in which they live. The case studies describe the unique ways in which participatory public art contributed to key recovery domains of growth in friendship, self-discovery, giving back, and hope. The two cases indicate that the development of a strengths-based sense of self through art was accompanied by a growth in personal social responsibility. The two cases also indicate that participatory public art may have a profound impact on the internalization of stigma. The findings support the value of participatory public art as a strategy for blending recovery and public health perspectives to promote both individual and community wellness.

  9. Comprehensive effective and efficient global public health surveillance

    Directory of Open Access Journals (Sweden)

    McNabb Scott JN

    2010-12-01

    Full Text Available Abstract At a crossroads, global public health surveillance exists in a fragmented state. Slow to detect, register, confirm, and analyze cases of public health significance, provide feedback, and communicate timely and useful information to stakeholders, global surveillance is neither maximally effective nor optimally efficient. Stakeholders lack a globa surveillance consensus policy and strategy; officials face inadequate training and scarce resources. Three movements now set the stage for transformation of surveillance: 1 adoption by Member States of the World Health Organization (WHO of the revised International Health Regulations (IHR[2005]; 2 maturation of information sciences and the penetration of information technologies to distal parts of the globe; and 3 consensus that the security and public health communities have overlapping interests and a mutual benefit in supporting public health functions. For these to enhance surveillance competencies, eight prerequisites should be in place: politics, policies, priorities, perspectives, procedures, practices, preparation, and payers. To achieve comprehensive, global surveillance, disparities in technical, logistic, governance, and financial capacities must be addressed. Challenges to closing these gaps include the lack of trust and transparency; perceived benefit at various levels; global governance to address data power and control; and specified financial support from globa partners. We propose an end-state perspective for comprehensive, effective and efficient global, multiple-hazard public health surveillance and describe a way forward to achieve it. This end-state is universal, global access to interoperable public health information when it’s needed, where it’s needed. This vision mitigates the tension between two fundamental human rights: first, the right to privacy, confidentiality, and security of personal health information combined with the right of sovereign, national entities

  10. Comprehensive effective and efficient global public health surveillance.

    Science.gov (United States)

    McNabb, Scott J N

    2010-12-03

    At a crossroads, global public health surveillance exists in a fragmented state. Slow to detect, register, confirm, and analyze cases of public health significance, provide feedback, and communicate timely and useful information to stakeholders, global surveillance is neither maximally effective nor optimally efficient. Stakeholders lack a globa surveillance consensus policy and strategy; officials face inadequate training and scarce resources.Three movements now set the stage for transformation of surveillance: 1) adoption by Member States of the World Health Organization (WHO) of the revised International Health Regulations (IHR[2005]); 2) maturation of information sciences and the penetration of information technologies to distal parts of the globe; and 3) consensus that the security and public health communities have overlapping interests and a mutual benefit in supporting public health functions. For these to enhance surveillance competencies, eight prerequisites should be in place: politics, policies, priorities, perspectives, procedures, practices, preparation, and payers.To achieve comprehensive, global surveillance, disparities in technical, logistic, governance, and financial capacities must be addressed. Challenges to closing these gaps include the lack of trust and transparency; perceived benefit at various levels; global governance to address data power and control; and specified financial support from globa partners.We propose an end-state perspective for comprehensive, effective and efficient global, multiple-hazard public health surveillance and describe a way forward to achieve it. This end-state is universal, global access to interoperable public health information when it's needed, where it's needed. This vision mitigates the tension between two fundamental human rights: first, the right to privacy, confidentiality, and security of personal health information combined with the right of sovereign, national entities to the ownership and stewardship

  11. The effect of care pathways for hip fractures: a systematic review.

    Science.gov (United States)

    Leigheb, Fabrizio; Vanhaecht, Kris; Sermeus, Walter; Lodewijckx, Cathy; Deneckere, Svin; Boonen, Steven; Boto, Paulo Alexandre Faria; Mendes, Rita Veloso; Panella, Massimiliano

    2012-07-01

    We performed a systematic review for primary studies on care pathways (CPs) for hip fracture (HF). The online databases MEDLINE-PubMed, Ovid-EMBASE, CINAHL-EBSCO host, and The Cochrane Library (Cochrane Central Register of Clinical Trials, Health Technology Assessment Database, NHS Economic Evaluation Database) were searched. Two researchers reviewed the literature independently. Primary studies that met predefined inclusion criteria were assessed for their methodological quality. A total of 15 publications were included: 15 primary studies corresponding with 12 main investigations. Primary studies were evaluated for clinical outcomes, process outcomes, and economic outcomes. The studies assessed a wide range of outcome measures. While a number of divergent clinical outcomes were reported, most studies showed positive results of process management and health-services utilization. In terms of mortality, the results provided evidence for a positive impact of CPs on in-hospital mortality. Most studies also showed a significantly reduced risk of complications, including medical complications, wound infections, and pressure sores. Moreover, time-span process measures showed that an improvement in the organization of care was achieved through the use of CPs. Conflicting results were observed with regard to functional recovery and mobility between patients treated with CPs compared to usual care. Although our review suggests that CPs can have positive effects in patients with HF, the available evidence is insufficient for formal recommendations. There is a need for more research on CPs with selected process and outcome indicators, for in-hospital and postdischarge management of HF, with an emphasis on well-designed randomized trials.

  12. Effects of matrine on JAK-STAT signaling transduction pathways in ...

    African Journals Online (AJOL)

    The current study aims to investigate the effects of matrine on the JAK-STAT signaling transduction pathways in bleomycin (BLM)-induced pulmonary fibrosis (PF) and to explore its action mechanism. A total of 72 male C57BL/6 mice were randomized into the control, model, and treatment groups. PF models were ...

  13. Antitumor effects of traditional Chinese medicine targeting the cellular apoptotic pathway

    Directory of Open Access Journals (Sweden)

    Xu HL

    2015-05-01

    Full Text Available Huanli Xu,1 Xin Zhao,2 Xiaohui Liu,1 Pingxiang Xu,1 Keming Zhang,2 Xiukun Lin11Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, 2Department of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation Army, Beijing, People’s Republic of ChinaAbstract: Defects in apoptosis are common phenomena in many types of cancer and are also a critical step in tumorigenesis. Targeting the apoptotic pathway has been considered an intriguing strategy for cancer therapy. Traditional Chinese medicine (TCM has been used in the People’s Republic of China for thousands of years, and many of the medicines have been confirmed to be effective in the treatment of a number of tumors. With increasing cancer rates worldwide, the antitumor effects of TCMs have attracted more and more attention globally. Many of the TCMs have been shown to have antitumor activity through multiple targets, and apoptosis pathway-related targets have been extensively studied and defined to be promising. This review focuses on several antitumor TCMs, especially those with clinical efficacy, based on their effects on the apoptotic signaling pathway. The problems with and prospects of development of TCMs as anticancer agents are also presented.Keywords: traditional Chinese medicine, antitumor effects, apoptotic pathway

  14. Perceived public health effects of occupational and residential ...

    African Journals Online (AJOL)

    This study was aimed at assessing the perceived public health effects of occupational and residential exposures to e-wastes in Alaba International and Computer Village markets, the two largest electronic markets in Lagos, Nigeria. A cross sectional, comparative study was carried out using questionnaire survey of randomly ...

  15. Public Management and Organizational Performance: The Effect of Managerial Quality

    NARCIS (Netherlands)

    O'Toole, Laurence J.; Meier, Kenneth J.

    2002-01-01

    This paper presents the first large study of public management quality and its effect on program performance. Using 5 years of data from more than 1000 Texas school districts, the authors measure quality as the additional salary paid to school superintendents over and above the normal determinants

  16. Effects of selling public intervention stocks of skimmed milk powder

    NARCIS (Netherlands)

    Jongeneel, Roel; Silvis, Huib; Verhoog, David; Daatselaar, Co

    2018-01-01

    At the request of the Dutch Ministry of Agriculture, Nature and Food Quality, this report analyses the potential market impacts and budgetary effects of different strategies of selling EU public intervention stocks of skimmed milk powder
    (SMP). A gradual phasing out of the EU's SMP stocks over

  17. The effectiveness of the Expanded Public Works Programme on job ...

    African Journals Online (AJOL)

    The effectiveness of the Expanded Public Works Programme on job creation: a look at a South African ... Open Access DOWNLOAD FULL TEXT ... This paper reports of a study that examined how the eThekwini Municipality's EPWP has been ...

  18. Effectiveness of infrastructure asset management: challenges for public agencies

    NARCIS (Netherlands)

    Schraven, Daan; Hartmann, Andreas; Dewulf, Geert P.M.R.

    2011-01-01

    Purpose: The aim of this research is to better understand the decisions in infrastructure asset management at public agencies and the challenges of these agencies to improve the effectiveness of their decision making. Design/methodology/approach: Based on a literature review on asset management at

  19. Assessing the full effects of public investment in space

    NARCIS (Netherlands)

    Clark, J.; Koopmans, C.C.; Hof, B.; Knee, P.; Lieshout, R.; Simmonds, P.; Wokke, F.

    2014-01-01

    Many space-related impact studies have been carried out in the past, but there is no conclusive, comprehensive evaluation of the economic and social effects of public investments in space. Such evaluations are not easy to perform, for several reasons: the space sector is not a recognised category in

  20. Branding your medical practice with effective public relations.

    Science.gov (United States)

    Trent, Nancy

    2009-01-01

    Whether you think of it as your image, your standing in the community, or your reputation, your medical practice is also a brand. While many organizations, companies, products, and services are known for specific attributes that make them stand out from competitors, most use a combination of marketing disciplines to communicate who and what they are to their customers, consumers, and patients. Public relations is often considered the most powerful, cost-effective, and efficacious of the marketing disciplines, surpassing advertising, promotion, and direct mail in molding and developing brands. Your practice can benefit from a well-crafted branding public relations program.

  1. Cost-effectiveness analysis of a postoperative clinical care pathway in head and neck surgery with microvascular reconstruction

    OpenAIRE

    Dautremont, Jonathan F; Rudmik, Luke R; Yeung, Justin; Asante, Tiffany; Nakoneshny, Steve C; Hoy, Monica; Lui, Amanda; Chandarana, Shamir P; Matthews, Thomas W; Schrag, Christiaan; Dort, Joseph C

    2013-01-01

    Background The objective of this study is to evaluate the cost-effectiveness of a postoperative clinical care pathway for patients undergoing major head and neck oncologic surgery with microvascular reconstruction. Methods This is a comparative trial of a prospective treatment group managed on a postoperative clinical care pathway and a historical group managed prior to pathway implementation. Effectiveness outcomes evaluated were total hospital days, return to OR, readmission to ICU and rate...

  2. Characterization of the Antioxidant Effects of γ-Oryzanol: Involvement of the Nrf2 Pathway

    OpenAIRE

    W. Rungratanawanich; G. Abate; M. M. Serafini; M. Guarienti; M. Catanzaro; M. Marziano; M. Memo; C. Lanni; D. Uberti

    2018-01-01

    γ-Oryzanol (ORY) is well known for its antioxidant potential. However, the mechanism by which ORY exerts its antioxidant effect is still unclear. In this paper, the antioxidant properties of ORY were investigated for its potential effects as a reactive oxygen and nitrogen species (ROS/RNS) scavenger and in activating antioxidant-promoting intracellular pathways utilizing the human embryonic kidney cells (HEK-293). The 24 h ORY exposure significantly prevented hydrogen peroxide- (H2O2-) induce...

  3. Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution

    OpenAIRE

    Shen, Yu-Sheng; Lung, Shih-Chun Candice

    2017-01-01

    Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, ...

  4. On the use of age-specific effective dose coefficients in radiation protection of the public

    International Nuclear Information System (INIS)

    Kocher, D.C.; Eckerman, K.F.

    1998-01-01

    Current radiation protection standards for the public include a limit on effective dose in any year for individuals in critical groups. This paper considers the question of how the annual dose limit should be applied in controlling routine exposures of populations consisting of individuals of all ages. We assume that the fundamental objective of radiation protection is limitation of lifetime risk and, therefore, that standards for controlling routine exposures of the public should provide a reasonable correspondence with lifetime risk, taking into account the age dependence of intakes and doses and the variety of radionuclides and exposure pathways of concern. Using new calculations of the per capita (population-averaged) risk of cancer mortality per unit activity inhaled or ingested in the U.S. Environmental Protection Agency's Federal Guidance Report No. 13, we show that applying a limit on annual effective dose only to adults, which was the usual practice in radiation protection of the public before the development of age-specific effective dose coefficients, provides a considerably better correspondence with lifetime risk that applying the annual dose limit to the critical group of any age. (author)

  5. On the use of age-specific effective dose coefficients in radiation protection of the public

    International Nuclear Information System (INIS)

    Kocher, D.C.; Eckerman, K.F.

    1998-01-01

    Current radiation protection standards for the public include a limit on effective dose in any year for individuals in critical groups. This paper considers the question of how the annual dose limit should be applied in controlling routine exposures of populations consisting of individuals of all ages. The authors assume that the fundamental objective of radiation protection is limitation of lifetime risk and, therefore, that standards for controlling routine exposures of the public should provide a reasonable correspondence with lifetime risk, taking into account the age dependence of intakes and doses and the variety of radionuclides and exposure pathways of concern. Using new calculations of the per capita (population-averaged) risk of cancer mortality per unit activity inhaled or ingested in the US Environmental Protection Agency's Federal Guidance Report No. 13, the authors show that applying a limit on annual effective dose only to adults, which was the usual practice in radiation protection of the public before the development of age-specific effective dose coefficients, provides a considerably better correspondence with lifetime risk than applying the annual dose limit to the critical group of any age

  6. Effect of assistive technology in a public school setting.

    Science.gov (United States)

    Watson, Anne H; Ito, Max; Smith, Roger O; Andersen, Lori T

    2010-01-01

    The Individuals With Disabilities Education Improvement Act of 2004 (IDEA) requires assistive technology (AT) be considered at the yearly individualized education program (IEP) meeting of every student in special education. IDEA also directs that AT be implemented on the basis of peer-reviewed literature despite a paucity of research on AT's effectiveness in the public schools. This repeated-measures quasi-experimental study explored AT's effect in a public school special education setting. Participants (N=13) were a heterogeneous group of students in 1 school system who had newly provided AT to address academic and communication goals in one school year. Results suggest that relative to other interventions, AT provided by a multidisciplinary team may have a significant effect on IEP goal improvement (t[12] = 5.54, p= .00) for students in special education (F[2] = 9.35, p= .00), which may support AT's use in special education by occupational therapists as directed by IDEA.

  7. Environmental remediation: Addressing public concerns through effective community relations

    International Nuclear Information System (INIS)

    Davis, S.; Heywood, J.; Wood, M.B.; Arellano, M.; Pfister, S.

    1998-01-01

    The public's perception of risk drives their response to any potential environmental remediation project. Even if the actual environmental and health risks may be relatively low, public perception of high risk may doom the project to an uphill struggle characterized by heated public meetings, negative media coverage, reluctant regulators, project delays and increased costs. The ultimate Catch 22 in such a case is that the contamination remains in-place until the public drama is concluded. This paper explores the development and implementation of a Community Relations Plan for the clean up of a Manufactured Gas Plant (MGP) site owned and operated by corporate predecessors of Arizona Public Service Company (APS) near the turn of the century. The unique challenges associated with this project were that the former MGP was located in downtown Phoenix at the site of a future federal courthouse. Although the MGP site had been under investigation for some time, the clean-up schedule was driven by a tight courthouse construction schedule. Compounding these challenges were the logistics associated with conducting a large-scale cleanup in a congested, highly visible downtown location. An effective Community Relations Plan can mean the difference between the success and failure of an environmental remediation project. Elements of an effective plan are: identifying key stakeholders and involving them in the project from the beginning; providing timely information and being open and honest about the potential environmental and health risks; involving your company's community relations and media staff; and educating affected company employees. The Community Relations Plan developed for this project was designed to alleviate public concern about potential risks (perceived or real) associated with the project by keeping key stakeholders informed of all activities well in advance

  8. The antitumor effects of geraniol: Modulation of cancer hallmark pathways (Review).

    Science.gov (United States)

    Cho, Minsoo; So, Insuk; Chun, Jung Nyeo; Jeon, Ju-Hong

    2016-05-01

    Geraniol is a dietary monoterpene alcohol that is found in the essential oils of aromatic plants. To date, experimental evidence supports the therapeutic or preventive effects of geraniol on different types of cancer, such as breast, lung, colon, prostate, pancreatic, and hepatic cancer, and has revealed the mechanistic basis for its pharmacological actions. In addition, geraniol sensitizes tumor cells to commonly used chemotherapy agents. Geraniol controls a variety of signaling molecules and pathways that represent tumor hallmarks; these actions of geraniol constrain the ability of tumor cells to acquire adaptive resistance against anticancer drugs. In the present review, we emphasize that geraniol is a promising compound or chemical moiety for the development of a safe and effective multi-targeted anticancer agent. We summarize the current knowledge of the effects of geraniol on target molecules and pathways in cancer cells. Our review provides novel insight into the challenges and perspectives with regard to geraniol research and to its application in future clinical investigation.

  9. Effect of Short-Circuit Pathways on Water Quality in Selected Confined Aquifers (Invited)

    Science.gov (United States)

    McMahon, P. B.

    2010-12-01

    Confined aquifers in the United States generally contain fewer anthropogenic contaminants than unconfined aquifers because confined aquifers often contain water recharged prior to substantial human development and redox conditions are more reducing, which favors degradation of common contaminants like nitrate and chlorinated solvents. Groundwater in a confined part of the High Plains aquifer near York, Nebraska had an adjusted radiocarbon age of about 2,000 years, and groundwater in a confined part of the Floridan aquifer near Tampa, Florida had apparent ages greater than 60 years on the basis of tritium measurements. Yet compounds introduced more recently into the environment (anthropogenic nitrate and volatile organic compounds) were detected in selected public-supply wells completed in both aquifers. Depth-dependent measurements of flow and chemistry in the pumping supply wells, groundwater age dating, numerical modeling of groundwater flow, and other monitoring data indicated that the confined aquifers sampled by the supply wells were connected to contaminated unconfined aquifers by short-circuit pathways. In the High Plains aquifer, the primary pathways appeared to be inactive irrigation wells screened in both the unconfined and confined aquifers. In the Floridan aquifer, the primary pathways were karst sinkholes and conduits. Heavy pumping in both confined systems exacerbated the problem by reducing the potentiometric surface and increasing groundwater velocities, thus enhancing downward gradients and reducing reaction times for processes like denitrification. From a broader perspective, several confined aquifers in the U.S. have experienced large declines in their potentiometric surfaces because of groundwater pumping and this could increase the potential for contamination in those aquifers, particularly where short-circuit pathways connect them to shallower, contaminated sources of water, such as was observed in York and Tampa.

  10. Kinase inhibitors can produce off-target effects and activate linked pathways by retroactivity

    Directory of Open Access Journals (Sweden)

    Wynn Michelle L

    2011-10-01

    Full Text Available Abstract Background It has been shown in experimental and theoretical work that covalently modified signaling cascades naturally exhibit bidirectional signal propagation via a phenomenon known as retroactivity. An important consequence of retroactivity, which arises due to enzyme sequestration in covalently modified signaling cascades, is that a downstream perturbation can produce a response in a component upstream of the perturbation without the need for explicit feedback connections. Retroactivity may, therefore, play an important role in the cellular response to a targeted therapy. Kinase inhibitors are a class of targeted therapies designed to interfere with a specific kinase molecule in a dysregulated signaling pathway. While extremely promising as anti-cancer agents, kinase inhibitors may produce undesirable off-target effects by non-specific interactions or pathway cross-talk. We hypothesize that targeted therapies such as kinase inhibitors can produce off-target effects as a consequence of retroactivity alone. Results We used a computational model and a series of simple signaling motifs to test the hypothesis. Our results indicate that within physiologically and therapeutically relevant ranges for all parameters, a targeted inhibitor can naturally induce an off-target effect via retroactivity. The kinetics governing covalent modification cycles in a signaling network were more important for propagating an upstream off-target effect in our models than the kinetics governing the targeted therapy itself. Our results also reveal the surprising and crucial result that kinase inhibitors have the capacity to turn "on" an otherwise "off" parallel cascade when two cascades share an upstream activator. Conclusions A proper and detailed characterization of a pathway's structure is important for identifying the optimal protein to target as well as what concentration of the targeted therapy is required to modulate the pathway in a safe and effective

  11. The policy debate over public investment in comparative effectiveness research.

    Science.gov (United States)

    Rich, Eugene C

    2009-06-01

    Policy makers across the political spectrum, as well as many clinicians and physician professional associations, have proposed that better information on comparative clinical effectiveness should be a key element of any solution to the US health-care cost crisis. This superficial consensus hides intense disagreements over critical issues essential to any new public effort to promote more comparative effectiveness research (CER). This article reviews the background for these disputes, summarizes the different perspectives represented by policy makers and advocates, and offers a framework to aid both practicing and academic internists in understanding the key elements of the emerging debate. Regarding the fundamental question of "what is CER," disagreements rage over whether value or cost effectiveness should be a consideration, and how specific patient perspectives should be reflected in the development and the use of such research. The question of how to pay for CER invokes controversies over the role of the market in producing such information and the private (e.g., insurers and employers) versus public responsibility for its production. The financing debate further highlights the high stakes of comparative effectiveness research, and the risks of stakeholder interests subverting any public process. Accordingly there are a range of proposals for the federal government's role in prioritization, development, and dissemination of CER. The internal medicine community, with its long history of commitment to scientific medical practice and its leadership in evidence-based medicine, should have a strong interest and play an active role in this debate.

  12. A cost-effective method of achieving meaningful citizen participation in public roadway pipeline studies

    Energy Technology Data Exchange (ETDEWEB)

    Buszynski, M.E.

    1996-12-31

    Many proponents of gas pipeline studies using the public roadway for their facilities have trouble encouraging public participation. Problems resulting from a lack of public involvement are documented. A public participation process designed to gather meaningful public input is presented through a case study of a public roadway pipeline study in southern Ontario. Techniques are outlined to effectively stimulate public interest and document the public involvement process. Recommendations are made as to the transferability of this process to other jurisdictions.

  13. Role of nitric oxide pathway in the conditioned rewarding effects of MDMA in mice.

    Science.gov (United States)

    García-Pardo, M P; Rodríguez-Arias, M; Miñarro, J; Aguilar, M A

    2017-07-14

    It is estimated that 2.1 million young adults used MDMA/Ecstasy in the last year in Europe. Vulnerable subjects can develop dependence after MDMA abuse but currently there does not exist an effective treatment for this disorder. The nitric oxide (NO) pathway seems to have an important role on the rewarding effects of different drugs and has been proposed as a new pharmacological treatment for psychostimulant addiction. In the present study, we intend to evaluate whether the blockade of the NO synthesis (NOS) interferes with the rewarding effects of MDMA in the conditioned preference place (CPP) paradigm in young adult male mice. Our results indicated that mice treated with 7-nitroindazole (a NOS inhibitor) did not show CPP after conditioning with MDMA (1.25mg/kg). These results demonstrated the role of the NO pathway in the rewarding effects of MDMA and suggested that the manipulation of this pathway could be a new therapeutic option for MDMA abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Effects of deep brain stimulation of the cerebellothalamic pathways on the sense of smell.

    Science.gov (United States)

    Kronenbuerger, M; Zobel, S; Ilgner, J; Finkelmeyer, A; Reinacher, P; Coenen, V A; Wilms, H; Kloss, M; Kiening, K; Daniels, C; Falk, D; Schulz, J B; Deuschl, G; Hummel, T

    2010-03-01

    The cerebellum and the motor thalamus, connected by cerebellothalamic pathways, are traditionally considered part of the motor-control system. Yet, functional imaging studies and clinical studies including patients with cerebellar disease suggest an involvement of the cerebellum in olfaction. Additionally, there are anecdotal clinical reports of olfactory disturbances elicited by electrical stimulation of the motor thalamus and its neighbouring subthalamic region. Deep brain stimulation (DBS) targeting the cerebellothalamic pathways is an effective treatment for essential tremor (ET), which also offers the possibility to explore the involvement of cerebellothalamic pathways in the sense of smell. This may be important for patient care given the increased use of DBS for the treatment of tremor disorders. Therefore, 21 none-medicated patients with ET treated with DBS (13 bilateral, 8 unilateral) were examined with "Sniffin' Sticks," an established and reliable method for olfactory testing. Patients were studied either with DBS switched on and then off or in reversed order. DBS impaired odor threshold and, to a lesser extent, odor discrimination. These effects were sub-clinical as none of the patients reported changes in olfactory function. The findings, however, demonstrate that olfaction can be modulated in a circumscribed area of the posterior (sub-) thalamic region. We propose that the impairment of the odor threshold with DBS is related to effects on an olfacto-motor loop, while disturbed odor discrimination may be related to effects of DBS on short-term memory. Copyright 2009 Elsevier Inc. All rights reserved.

  15. In the Name of Effective Consumer Protection and Public Policy!

    DEFF Research Database (Denmark)

    Sørensen, Marie Jull

    2016-01-01

    I. The CJEU has established that under certain circumstances national courts have an obligation, ex officio, to apply specific consumer protection provisions. This article presents a model derived from the argumentation for this obligation in CJEU case law. The model consists of four steps...... that include the specific ideas behind consumer protection provisions as well as the interaction between the principle of effectiveness and principle of equivalence. It is found that the principle of effectiveness is stretched very long and is often not set aside by the “rule of reason”. It is also found...... that the CJEU is open to the idea of regarding consumer protection provisions as (EU) public policy rules which seems to challenge the traditional principle of equivalence. Based on the findings, the author elaborates on the concept of an European public policy doctrine....

  16. A procurement-based pathway for promoting public health: innovative purchasing approaches for state and local government agencies.

    Science.gov (United States)

    Noonan, Kathleen; Miller, Dorothy; Sell, Katherine; Rubin, David

    2013-11-01

    Through their purchasing powers, government agencies can play a critical role in leveraging markets to create healthier foods. In the United States, state and local governments are implementing creative approaches to procuring healthier foods, moving beyond the traditional regulatory relationship between government and vendors. They are forging new partnerships between government, non-profits, and researchers to increase healthier purchasing. On the basis of case examples, this article proposes a pathway in which state and local government agencies can use the procurement cycle to improve healthy eating.

  17. Effects of ambroxol on the autophagy-lysosome pathway and mitochondria in primary cortical neurons.

    Science.gov (United States)

    Magalhaes, J; Gegg, M E; Migdalska-Richards, A; Schapira, A H

    2018-01-23

    Glucocerebrosidase (GBA1) mutations are the major genetic risk factor for Parkinson's Disease (PD). The pathogenic mechanism is still unclear, but alterations in lysosomal-autophagy processes are implicated due to reduction of mutated glucocerebrosidase (GCase) in lysosomes. Wild-type GCase activity is also decreased in sporadic PD brains. Small molecule chaperones that increase lysosomal GCase activity have potential to be disease-modifying therapies for GBA1-associated and sporadic PD. Therefore we have used mouse cortical neurons to explore the effects of the chaperone ambroxol. This chaperone increased wild-type GCase mRNA, protein levels and activity, as well as increasing other lysosomal enzymes and LIMP2, the GCase transporter. Transcription factor EB (TFEB), the master regulator of the CLEAR pathway involved in lysosomal biogenesis was also increased upon ambroxol treatment. Moreover, we found macroautophagy flux blocked and exocytosis increased in neurons treated with ambroxol. We suggest that ambroxol is blocking autophagy and driving cargo towards the secretory pathway. Mitochondria content was also found to be increased by ambroxol via peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α). Our data suggest that ambroxol, besides being a GCase chaperone, also acts on other pathways, such as mitochondria, lysosomal biogenesis, and the secretory pathway.

  18. Public Health Effects of Medical Marijuana Legalization in Colorado.

    Science.gov (United States)

    Davis, Jonathan M; Mendelson, Bruce; Berkes, Jay J; Suleta, Katie; Corsi, Karen F; Booth, Robert E

    2016-03-01

    The public health consequences of the legalization of marijuana, whether for medical or recreational purposes, are little understood. Despite this, numerous states are considering medical or recreational legalization. In the context of abrupt changes in marijuana policy in 2009 in Colorado, the authors sought to investigate corresponding changes in marijuana-related public health indicators. This observational, ecologic study used an interrupted time-series analysis to identify changes in public health indicators potentially related to broad policy changes that occurred in 2009. This was records-based research from the state of Colorado and Denver metropolitan area. Data were collected to examine frequency and trends of marijuana-related outcomes in hospital discharges and poison center calls between time periods before and after 2009 and adjusted for population. Analyses were conducted in 2014. Hospital discharges coded as marijuana-dependent increased 1% per month (95% CI=0.8, 1.1, pcenter calls mentioning marijuana (pcenter calls increased 0.8% per month (95% CI=0.2, 1.4, pcenter calls also increased 56% (95% CI=49%, 63%, p<0.001) in the period following the policy change. Further, there was one hospital discharge coded as dependent for every 3,159 (95% CI=2465, 3853, p<0.001) medical marijuana registrant applications. The abrupt nature of these changes suggests public health effects related to broad policy changes associated with marijuana. This report may be used to assist in policy decisions regarding the short-term public health effects of marijuana legalization. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  19. [Public music concerts in a psychiatric hospital: effects on public opinion and as therapy for patients].

    Science.gov (United States)

    Takasaka, Y; Yokota, O; Tanioka, T; Nagata, K; Yasuoka, K; Toda, H

    2001-01-01

    We investigate the effects of music therapy concerts, which were held 60 times over a four year period, 1992 to 1996, in Geiyo Psychiatric Hospital, Kochi Prefecture and found that; 1) Musicians who performed at the concerts were not only from Kochi prefecture but also from other prefectures (10 times) and from four foreign countries (7 times). 2) Live concerts in a small hall had a positive influence on patients and drew the patient's attention and interest away from their hallucinations and delusions to the real world. Moreover, the concerts provided the patients with chances to acquire social graces such as being well-groomed. 3) Explanations by the musicians, interviews with the musicians and the seasonal choruses accompanied by the musicians were helpful to give the patients motives for recovering communication skills and to interact with society. 4) Inquiries to the patients about the concerts indicated discrepancies between the poor observed estimations during the concerts (83.3%) and the good subjective impressions expressed by the patients (82.0%), suggesting that the patients were not good at expressing their internal emotions through facial expressions or attitudes. 5) Many citizens including children came to the concerts and/or gave aid to the hospital because the concerts were open to the public and we suggest that this contributed to improving the general publics' image of psychiatric hospitals. Questionnaires revealed that 90% of people in a control group had a bad image of psychiatric hospitals in Japan, but only 32% of the members of the general public who attended our concerts had a bad image of psychiatric hospitals. In addition, the revolving ratio of the hospital beds rose from 0.4 to 1.2 over the four years, which also suggests a beneficial effect on the patients.

  20. Informing the public on technical effectiveness of international safeguards

    International Nuclear Information System (INIS)

    Hunt, H.M.

    1994-01-01

    In recent years, public interest regarding IAEA (International Atomic Energy Agency) safeguards effectiveness has partially shifted to detection of undeclared nuclear facilities. Nevertheless, important segments of the public remain vitally interested in whether international safeguards would be able to reliably and definitively detect diversion of bomb quantities of plutonium or highly enriched uranium from open-quotes bulk handlingclose quotes facilities. There now exists a sizable body of unclassified technical reports, based on experimental results over many years, written by various experts, describing actual capabilities and limitations of safeguards techniques and systems, which collectively lead to definitive evaluations of technical safeguards effectiveness. For a large-scale operation of spent fuel reprocessing, plutonium fuel fabrication, or gas centrifuge uranium enrichment, an undisputable conclusion is that international safeguards systems would be unable to reliably and definitively detect the diversion in a one-year period of a significant quantity of plutonium or enriched uranium; moreover, diversion of many significant quantities per year (from such an operation) would have negligible probability of definitive detection if conducted in accordance with particle diversion scenarios. To properly inform the public and government agencies, reports on technical effectiveness of international safeguards should incorporate these basic conclusions

  1. Gender dimensions of rural employment in agriculture and public works programmes experiences from South Africa: Differentiated pathways out of poverty

    CSIR Research Space (South Africa)

    Mashiri, M

    2010-12-01

    Full Text Available rural livelihoods (Department of Public Works, 1997). It also addresses gender dimensions of the projects. As methodology, a mixed-method approach was employed to assess the experiences and impacts of the Siyatentela 56 (Mpumalanga Province), Gundo Lashu...

  2. A cluster randomized trial to assess the impact of clinical pathways for patients with stroke: rationale and design of the Clinical Pathways for Effective and Appropriate Care Study [NCT00673491

    Directory of Open Access Journals (Sweden)

    Barbieri Antonella

    2008-11-01

    Full Text Available Abstract Background Patients with stroke should have access to a continuum of care from organized stroke units in the acute phase, to appropriate rehabilitation and secondary prevention measures. Moreover to improve the outcomes for acute stroke patients from an organizational perspective, the use of multidisciplinary teams and the delivery of continuous stroke education both to the professionals and to the public, and the implementation of evidence-based stroke care are recommended. Clinical pathways are complex interventions that can be used for this purpose. However in stroke care the use of clinical pathways remains questionable because little prospective controlled data has demonstrated their effectiveness. The purpose of this study is to determine whether clinical pathways could improve the quality of the care provided to the patients affected by stroke in hospital and through the continuum of the care. Methods Two-arm, cluster-randomized trial with hospitals and rehabilitation long-term care facilities as randomization units. 14 units will be randomized either to arm 1 (clinical pathway or to arm 2 (no intervention, usual care. The sample will include 238 in each group, this gives a power of 80%, at 5% significance level. The primary outcome measure is 30-days mortality. The impact of the clinical pathways along the continuum of care will also be analyzed by comparing the length of hospital stay, the hospital re-admissions rates, the institutionalization rates after hospital discharge, the patients' dependency levels, and complication rates. The quality of the care provided to the patients will be assessed by monitoring the use of diagnostic and therapeutic procedures during hospital stay and rehabilitation, and by the use of key quality indicators at discharge. The implementation of organized care will be also evaluated. Conclusion The management of patients affected by stroke involves the expertise of several professionals, which can

  3. The cost-effectiveness of public postsecondary education subsidies.

    Science.gov (United States)

    Muennig, P; Fahs, M

    2001-02-01

    Although educational attainment is a well-recognized covariate of health status, it is rarely thought of as a tool to be used to improve health. Since fewer than 40% of U.S. citizens have a college degree, it may be possible for the government to improve the health status of the population by assuming a larger burden of the cost of postsecondary education. This paper examines the costs and health effects of a government subsidy for public postsecondary education institutions. All high school graduates in 1997 were included in a decision analysis model as a hypothetical cohort. Data from the U.S. Department of Education, the World Health Organization, and the National Center for Health Statistics were used as model inputs. Results. Relative to the present educational system, a federal subsidy for public and private colleges equal to the amount now paid by students for tuition and living expenses would save $6,176 and avert 0.0018 of a disability-adjusted life-year (DALY) per person annually if enrollment increased 5%. The overall savings among 1997 high school graduates would be $17.1 billion and 4,992 DALYs would be averted per year relative to the present educational system. If enrollment increased by just 3%, $3,743 would be saved and 0.0011 DALYs would be averted per person. An enrollment increase of 7% would lead to savings of $8,610 and 0.0025 DALYs would be averted per person relative to the present educational system. If the government were to offer a full subsidy for college tuition at public universities, both lives and money would be saved, so long as enrollment levels increased. Providing a free postsecondary education for students attending public schools may be more cost-effective than most health investments. Copyright 2001 American Health Foundation and Academic Press.

  4. Sesamol induced apoptotic effect in lung adenocarcinoma cells through both intrinsic and extrinsic pathways.

    Science.gov (United States)

    Siriwarin, Boondaree; Weerapreeyakul, Natthida

    2016-07-25

    Sesamol is a phenolic lignan found in sesame seeds (Sesamum indicum L.) and sesame oil. The anticancer effects and molecular mechanisms underlying its apoptosis-inducing effect were investigated in human lung adenocarcinoma (SK-LU-1) cells. Sesamol inhibited SK-LU-1 cell growth with an IC50 value of 2.7 mM and exhibited less toxicity toward normal Vero cells after 48 h of treatment (Selective index = 3). Apoptotic bodies-the hallmark of apoptosis-were observed in sesamol-treated SK-LU-1 cells, stained with DAPI. Sesamol increased the activity of caspase 8, 9, and 3/7, indicating that apoptotic cell death occurred through both extrinsic and intrinsic pathways. Sesamol caused the loss of mitochondrial transmembrane potential signifying intrinsic apoptosis induction. Decreasing Bid expression revealed crosstalk between the intrinsic and extrinsic apoptotic pathways; demonstrating clearly that sesamol induces apoptosis through both pathways in human lung adenocarcinoma (SK-LU-1) cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Organophosphate pesticides exposure among farmworkers: pathways and risk of adverse health effects.

    Science.gov (United States)

    Suratman, Suratman; Edwards, John William; Babina, Kateryna

    2015-01-01

    Organophosphate (OP) compounds are the most widely used pesticides with more than 100 OP compounds in use around the world. The high-intensity use of OP pesticides contributes to morbidity and mortality in farmworkers and their families through acute or chronic pesticides-related illnesses. Many factors contributing to adverse health effects have been investigated by researchers to determine pathways of OP-pesticide exposure among farmers in developed and developing countries. Factors like wind/agricultural pesticide drift, mixing and spraying pesticides, use of personal protective equipment (PPE), knowledge, perceptions, washing hands, taking a shower, wearing contaminated clothes, eating, drinking, smoking, and hot weather are common in both groups of countries. Factors including low socioeconomic status areas, workplace conditions, duration of exposure, pesticide safety training, frequency of applying pesticides, spraying against the wind, and reuse of pesticide containers for storage are specific contributors in developing countries, whereas housing conditions, social contextual factors, and mechanical equipment were specific pathways in developed countries. This paper compares existing research in environmental and behavioural exposure modifying factors and biological monitoring between developing and developed countries. The main objective of this review is to explore the current depth of understanding of exposure pathways and factors increasing the risk of exposure potentially leading to adverse health effects specific to each group of countries.

  6. Effect of a redesigned fracture management pathway and 'virtual' fracture clinic on ED performance.

    Science.gov (United States)

    Vardy, J; Jenkins, P J; Clark, K; Chekroud, M; Begbie, K; Anthony, I; Rymaszewski, L A; Ireland, A J

    2014-06-13

    Collaboration between the orthopaedic and emergency medicine (ED) services has resulted in standardised treatment pathways, leaflet supported discharge and a virtual fracture clinic review. Patients with minor, stable fractures are discharged with no further follow-up arranged. We aimed to examine the time taken to assess and treat these patients in the ED along with the rate of unplanned reattendance. A retrospective study was undertaken that covered 1 year before the change and 1 year after. Prospectively collected administrative data from the electronic patient record system were analysed and compared before and after the change. An ED and orthopaedic unit, serving a population of 300 000, in a publicly funded health system. 2840 patients treated with referral to a traditional fracture clinic and 3374 patients managed according to the newly redesigned protocol. Time for assessment and treatment of patients with orthopaedic injuries not requiring immediate operative management, and 7-day unplanned reattendance. Where plaster backslabs were replaced with removable splints, the consultation time was reduced. There was no change in treatment time for other injuries treated by the new discharge protocol. There was no increase in unplanned ED attendance, related to the injury, within 7 days (p=0.149). There was a decrease in patients reattending the ED due to a missed fracture clinic appointment. This process did not require any new time resources from the ED staff. This process brought significant benefits to the ED as treatment pathways were agreed. The pathway reduced unnecessary reattendance of patients at face-to-face fracture clinics for a review of stable, self-limiting injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. The effect of giant lateral collapses on magma pathways and the location of volcanism.

    Science.gov (United States)

    Maccaferri, Francesco; Richter, Nicole; Walter, Thomas R

    2017-10-23

    Flank instability and lateral collapse are recurrent processes during the structural evolution of volcanic edifices, and they affect and are affected by magmatic activity. It is known that dyke intrusions have the potential to destabilise the flanks of a volcano, and that lateral collapses may change the style of volcanism and the arrangement of shallow dykes. However, the effect of a large lateral collapse on the location of a new eruptive centre remains unclear. Here, we use a numerical approach to simulate the pathways of magmatic intrusions underneath the volcanic edifice, after the stress redistribution resulting from a large lateral collapse. Our simulations are quantitatively validated against the observations at Fogo volcano, Cabo Verde. The results reveal that a lateral collapse can trigger a significant deflection of deep magma pathways in the crust, favouring the formation of a new eruptive centre within the collapse embayment. Our results have implications for the long-term evolution of intraplate volcanic ocean islands.

  8. Effect of deregulation of Sonic Hedgehog pathway on responses to DNA damage and cancer predisposition

    International Nuclear Information System (INIS)

    Charazac, Aurelie

    2015-01-01

    The Gorlin syndrome is a rare genetic disorder characterized by several developmental abnormalities. Due to mutations in PTCH1, a key player of the sonic hedgehog signaling pathway, clinical manifestations also includes hyper-radiosensitivity and an increased predisposition to the development of basal cell carcinomas. Given the implication of DNA repair system defects in hyper-radiosensitivity pathologies, we decided to study the effect of PTCH1 mutations on the DNA damage response in order to better understand the cellular and molecular mechanisms leading to Gorlin's phenotype.This study demonstrate a global failure of the DNA damage repair systems in Gorlin fibroblasts with respect to controls. It highlights in particular the collapse of the base excision repair pathway (BER) responsible for the repair of oxidative DNA damage. (author) [fr

  9. The effect of aquaporin 5 overexpression on the Ras signaling pathway

    International Nuclear Information System (INIS)

    Woo, Janghee; Lee, Juna; Kim, Myoung Sook; Jang, Se Jin; Sidransky, David; Moon, Chulso

    2008-01-01

    Human aquaporin 5 (AQP5) has been shown to be overexpressed in multiple cancers, such as pancreatic cancer and colon cancer. Furthermore, it has been reported that ectopic expression of AQP5 leads to many phenotypic changes characteristic of transformation. However, the biochemical mechanism leading to transformation in AQP5-overexpressing cells has not been clearly elucidated. In this report, the overexpression of AQP5 in NIH3T3 cells demonstrated a significant effect on Ras activity and, thus, cell proliferation. Furthermore, this influence was shown to be mediated by phosphorylation of the PKA consensus site of AQP5. This is the first evidence demonstrating an association between AQP5 and a signaling pathway, namely the Ras signal transduction pathway, which may be the basis of the oncogenic properties seen in AQP-overexpressing cells

  10. An Association Map on the Effect of Flavonoids on the Signaling Pathways in Colorectal Cancer.

    Science.gov (United States)

    Koosha, Sanaz; Alshawsh, Mohammed A; Looi, Chung Yeng; Seyedan, Atefehalsadat; Mohamed, Zahurin

    2016-01-01

    Colorectal cancer (CRC) is the third most common type of cancer in the world, causing thousands of deaths annually. Although chemotherapy is known to be an effective treatment to combat colon cancer, it produces severe side effects. Natural products, on the other hand, appear to generate fewer side effects than do chemotherapeutic drugs. Flavonoids are polyphenolic compounds found in various fruits and vegetables known to possess antioxidant activities, and the literature shows that several of these flavonoids have anti-CRC propertiesFlavonoids are classified into five main subclasses: flavonols, flavanones, flavones, flavan-3-ols, and flavanonols. Of these subclasses, the flavanonols have a minimum effect against CRC, whereas the flavones play an important role. The main targets for the inhibitory effect of flavonoids on CRC signaling pathways are caspase; nuclear factor kappa B; mitogen-activated protein kinase/p38; matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9; p53; β-catenin; cyclin-dependent kinase (CDK)2 and CDK4; and cyclins A, B, D, and E. In this review article, we summarize the in vitro and in vivo studies that have been performed since 2000 on the anti-CRC properties of flavonoids. We also describe the signaling pathways affected by flavonoids that have been found to be involved in CRC. Some flavonoids have the potential to be an effective alternative to chemotherapeutic drugs in the treatment of colon cancer; well-controlled clinical studies should, however, be conducted to support this proposal.

  11. Molecular Signaling Pathways Behind the Biological Effects of Salvia Species Diterpenes in Neuropharmacology and Cardiology.

    Science.gov (United States)

    Akaberi, M; Iranshahi, M; Mehri, S

    2016-06-01

    The genus Salvia, from the Lamiaceae family, has diverse biological properties that are primarily attributable to their diterpene contents. There is no comprehensive review on the molecular signaling pathways of these active components. In this review, we investigated the molecular targets of bioactive Salvia diterpenes responsible for the treatment of nervous and cardiovascular diseases. The effects on different pathways, including apoptosis signaling, oxidative stress phenomena, the accumulation of amyloid beta plaques, and tau phosphorylation, have all been considered to be mechanisms of the anti-Alzheimer properties of Salvia diterpenes. Additionally, effects on the benzodiazepine and kappa opioid receptors and neuroprotective effects are noted as neuropharmacological properties of Salvia diterpenes, including tanshinone IIA, salvinorin A, cryptotanshinone, and miltirone. Tanshinone IIA, as the primary diterpene of Salvia miltiorrhiza, has beneficial activities in heart diseases because of its ability to scavenge free radicals and its effects on transcription factors, such as nuclear transcription factor-kappa B (NF-κB) and the mitogen-activated protein kinases (MAPKs). Additionally, tanshinone IIA has also been proposed to have cardioprotective properties including antiarrhythmic activities and effects on myocardial infarction. With respect to the potential therapeutic effects of Salvia diterpenes, comprehensive clinical trials are warranted to evaluate these valuable molecules as lead compounds. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. The Pathway to a Safe and Effective Medication Formulary for Exploration Spaceflight

    Science.gov (United States)

    Daniels, V. R.; Bayuse, T. M.; Mulcahy, R. A.; Mcguire, R. K. M.; Antonsen, E. L.

    2017-01-01

    PURPOSE: Exploration space missions pose several challenges to providing a comprehensive medication formulary designed to accommodate the size and space limitations of the spacecraft; while addressing the individual medications needs and preferences of the Crew; the negative outcome of a degrading inventory over time, the inability to resupply before expiration dates; and the need to properly forecast the best possible medication candidates to treat conditions that will occur in the future. METHODS: The Pharmacotherapeutics Discipline has partnered with the Exploration Medical Capabilities (ExMC) Element to develop and propose a research pathway that is comprehensively focused on evidence-based models and theories, as well as on new diagnostic tools and treatments or preventive measures aimed at closure of the Med02 “Pharmacy” Gap; defined in the Human Research Program’s (HRP) risk-based research strategy. The Med02 Gap promotes the challenge to identify a strategy to ensure that medications used to treat medical conditions during exploration space missions are available, safe, and effective. It is abundantly clear that pharmaceutical intervention is an essential component of risk management planning for astronaut healthcare during exploration space. However, the quandary still remains of how to assemble a formulary that is comprehensive enough to prevent or treat anticipated medical events; and is also chemically stable, safe, and robust enough to have sufficient potency to last for the duration of an exploration space mission. In cases where that is not possible, addressing this Gap requires exploration of novel drug development techniques, dosage forms, and dosage delivery platforms that enhance chemical stability as well as therapeutic effectiveness. RESULTS: The proposed research pathway outlines the steps, processes, procedures, and a research portfolio aimed at identifying a capability that will provide a safe and effective pharmacy for any specific

  13. Public good provision and public bad prevention: the effect of framing

    NARCIS (Netherlands)

    Sonnemans, J.H.; Schram, A.J.H.C.; Offerman, T.J.S.

    1998-01-01

    An experimental analysis of voluntary, binary contributions for step-level public goods (bads) is presented. In the public good presentation of the dilemma the subjects choose between contributing or not. The public good is provided for all group-members if and only if the number of contributors

  14. Public good provision and public bad prevention: The effect of framing.

    NARCIS (Netherlands)

    Sonnemans, J.; Schram, A.; Offermans, T.

    1998-01-01

    An experimental analysis of voluntary, binary contributions for step-level public goods/bads is presented. Alternatively, the situation is presented as the provision of a public good or the prevention of a public bad. From a strategic point of view, these presentations are equivalent. In early

  15. Optional contributions have positive effects for volunteering public goods games

    Science.gov (United States)

    Song, Qi-Qing; Li, Zhen-Peng; Fu, Chang-He; Wang, Lai-Sheng

    2011-11-01

    Public goods (PG) games with the volunteering mechanism are referred to as volunteering public goods (VPG) games, in which loners are introduced to the PG games, and a loner obtains a constant payoff but not participating the game. Considering that small contributions may have positive effects to encourage more players with bounded rationality to contribute, this paper introduces optional contributions (high value or low value) to these typical VPG games-a cooperator can contribute a high or low payoff to the public pools. With the low contribution, the logit dynamics show that cooperation can be promoted in a well mixed population comparing to the typical VPG games, furthermore, as the multiplication factor is greater than a threshold, the average payoff of the population is also enhanced. In spatial VPG games, we introduce a new adjusting mechanism that is an approximation to best response. Some results in agreement with the prediction of the logit dynamics are found. These simulation results reveal that for VPG games the option of low contributions may be a better method to stimulate the growth of cooperation frequency and the average payoff of the population.

  16. Exploring communication pathways to better health: Clinician communication of expectations for acupuncture effectiveness

    Science.gov (United States)

    Street, Richard L.; Cox, Vanessa; Kallen, Michael A.; Suarez-Almazor, Maria E.

    2012-01-01

    Objective This study tested a pathway whereby acupuncturists’ communication of optimism for treatment effectiveness would enhance patients’ satisfaction during treatment, which in turn would contribute to better pain and function outcomes for patients with osteoarthritis of the knee. Methods Secondary analysis from a 2 arm (real vs. sham acupuncture, high vs. neutral expectations) RCT. 311 patients with knee osteoarthritis received acupuncture over 10–12 sessions. Coders rated the degree to which acupuncturists communicated optimism for the treatment’s effectiveness. Satisfaction with acupuncture was assessed 4 weeks into treatment. Pain and function were assessed 6 weeks following treatment. Results Patients experiencing better outcomes were more satisfied with acupuncture during treatment, were younger, and had better baseline pain and function scores. Satisfaction during treatment was greater when patients interacted with more optimistic clinicians and had higher pretreatment expectations for acupuncture efficacy. Conclusion Acupuncturists’ communication of optimism about treatment effectiveness contributed to pain and function outcomes indirectly through its effect on satisfaction during treatment. Future research should model pathways through which clinician-patient communication affects mediating variables that in turn lead to improved health outcomes. Practical Implications While clinicians should not mislead patients, communicating hope and optimism for treatment effectiveness has therapeutic value for patients. PMID:22857778

  17. Route effect on the perception of public transport services quality

    Energy Technology Data Exchange (ETDEWEB)

    Chica-Olmo, J.; Gachs-Sanchez, H.M.; Lizarraga, C.

    2016-07-01

    User satisfaction sets a basic example for public service quality, especially those considered as basic necessities. The quality in transport service related to conceptualization and measurement, as a decisive demand key, presents challenges for both economic and mobility policies.Several operator companies are involved in the transport sector. Therefore this report aims to design a model of overall satisfaction based on the level of satisfaction with a specific set of factors, considering individual characteristics of users and the differential effect of different bus lines.The current presentation has applied a combined method, using Nonlinear Principal Component Analysis (NLPCA) and a Logit Multilevel Model (LMLM) in two-steps. (Author)

  18. THE EFFECTIVENESS OF BUDGET ALLOCATION IN PUBLIC PROCUREMENT

    Directory of Open Access Journals (Sweden)

    Irina Yu. Fedorova

    2015-01-01

    Full Text Available This article deals with the problem of budget allocation in the state order inRussia. Assesses the effectiveness of the financial mechanism of the public procurement business entities, purchasing activities are regulated by Federal Law №44-FZ and №223-FZ. The dynamics of financing the procurement process and reveal its features by using the most common methods of procurement through competitive bidding and without bidding. Identifies the causes of inefficient spending budget as a result of the non-competitive procurement methods by certain categories of business entities. 

  19. Expert elicitation on ultrafine particles: likelihood of health effects and causal pathways

    Directory of Open Access Journals (Sweden)

    Brunekreef Bert

    2009-07-01

    Full Text Available Abstract Background Exposure to fine ambient particulate matter (PM has consistently been associated with increased morbidity and mortality. The relationship between exposure to ultrafine particles (UFP and health effects is less firmly established. If UFP cause health effects independently from coarser fractions, this could affect health impact assessment of air pollution, which would possibly lead to alternative policy options to be considered to reduce the disease burden of PM. Therefore, we organized an expert elicitation workshop to assess the evidence for a causal relationship between exposure to UFP and health endpoints. Methods An expert elicitation on the health effects of ambient ultrafine particle exposure was carried out, focusing on: 1 the likelihood of causal relationships with key health endpoints, and 2 the likelihood of potential causal pathways for cardiac events. Based on a systematic peer-nomination procedure, fourteen European experts (epidemiologists, toxicologists and clinicians were selected, of whom twelve attended. They were provided with a briefing book containing key literature. After a group discussion, individual expert judgments in the form of ratings of the likelihood of causal relationships and pathways were obtained using a confidence scheme adapted from the one used by the Intergovernmental Panel on Climate Change. Results The likelihood of an independent causal relationship between increased short-term UFP exposure and increased all-cause mortality, hospital admissions for cardiovascular and respiratory diseases, aggravation of asthma symptoms and lung function decrements was rated medium to high by most experts. The likelihood for long-term UFP exposure to be causally related to all cause mortality, cardiovascular and respiratory morbidity and lung cancer was rated slightly lower, mostly medium. The experts rated the likelihood of each of the six identified possible causal pathways separately. Out of these

  20. Research progress in the radioprotective effect of the canonical Wnt pathway

    International Nuclear Information System (INIS)

    Wang, Jin-Feng; Liu, Chao; Zhang, Qu; Huang, Guan-Hong

    2013-01-01

    Irradiation from diverse sources is ubiquitous and closely associated with human activities. Radiation therapy (RT), an important component of multiple radiation origins, is a common therapeutic modality for cancer. More importantly, RT provides significant contribution to oncotherapy by killing tumor cells. However, during the course of therapy, irradiation of normal tissues can result in a wide range of side effects, including self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. Although numerous promising radioprotective agents have emerged, only a few have successfully entered the market because of various limitations. At present, the widely accepted hypothesis for protection against radiation-caused injury involves the Wnt canonical pathway. Activating the Wnt/β-catenin signaling pathway may protect the salivary gland, oral mucosa, and gastrointestinal epithelium from radiation damage. The underlying mechanisms include inhibiting apoptosis and preserving normal tissue functions. However, aberrant Wnt signaling underlies a wide range of pathologies in humans, and its various components contribute to cancer. Moreover, studies have suggested that Wnt/β-catenin signaling may lead to radioresistance of cancer stem cell. These facts markedly complicate any definition of the exact function of the Wnt pathway

  1. Spatial localization of the first and last enzymes effectively connects active metabolic pathways in bacteria.

    Science.gov (United States)

    Meyer, Pablo; Cecchi, Guillermo; Stolovitzky, Gustavo

    2014-12-14

    Although much is understood about the enzymatic cascades that underlie cellular biosynthesis, comparatively little is known about the rules that determine their cellular organization. We performed a detailed analysis of the localization of E.coli GFP-tagged enzymes for cells growing exponentially. We found that out of 857 globular enzymes, at least 219 have a discrete punctuate localization in the cytoplasm and catalyze the first or the last reaction in 60% of biosynthetic pathways. A graph-theoretic analysis of E.coli's metabolic network shows that localized enzymes, in contrast to non-localized ones, form a tree-like hierarchical structure, have a higher within-group connectivity, and are traversed by a higher number of feed-forward and feedback loops than their non-localized counterparts. A Gene Ontology analysis of these enzymes reveals an enrichment of terms related to essential metabolic functions in growing cells. Given that these findings suggest a distinct metabolic role for localization, we studied the dynamics of cellular localization of the cell wall synthesizing enzymes in B. subtilis and found that enzymes localize during exponential growth but not during stationary growth. We conclude that active biochemical pathways inside the cytoplasm are organized spatially following a rule where their first or their last enzymes localize to effectively connect the different active pathways and thus could reflect the activity state of the cell's metabolic network.

  2. Effects of electromagnetic fields exposure on plasma hormonal and inflammatory pathway biomarkers in male workers of a power plant

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhaopin; Fei, Ying; Liu, Hui [Zhejiang Univ., Hangzhou (China). Dept. of Epidemiology and Health Statistics; Zhejiang Univ., Hangzhou (China). Chronic Disease Research Inst.; and others

    2016-01-15

    The potential health risks of electromagnetic fields (EMFs) have currently raised considerable public concerns. The aim of this study was to evaluate the effects of EMF exposure on levels of plasma hormonal and inflammatory pathway biomarkers in male workers of an electric power plant. Seventy-seven male workers with high occupational EMF exposure and 77 male controls with low exposure, matched by age, were selected from a cross-sectional study. Moreover, high EMF exposure group was with walkie-talkies usage and exposed to power frequency EMF at the work places for a longer duration than control group. A questionnaire was applied to obtain relevant information, including sociodemographic characteristics, lifestyle factors, and EMF exposures. Plasma levels of testosterone, estradiol, melatonin, NF-KB, heat-shock protein (HSP) 70, HSP27, and TET1 were determined by an enzyme-linked immunosorbent assay. EMF exposure group had statistically significantly lower levels of testosterone (β = -0.3 nmol/L, P = 0.015), testosterone/estradiol (T/E2) ratio (β = -15.6, P = 0.037), and NF-KB (β = -20.8 ng/L, P = 0.045) than control group. Moreover, joint effects between occupational EMF exposure and employment duration, mobile phone fees, years of mobile phone usage, and electric fees on levels of testosterone and T/E2 ratio were observed. Nevertheless, no statistically significant associations of EMF exposures with plasma estradiol, melatonin, HSP70, HSP27, and TET1 were found. The findings showed that chronic exposure to EMF could decrease male plasma testosterone and T/E2 ratio, and it might possibly affect reproductive functions in males. No significant associations of EMF exposure with inflammatory pathway biomarkers were found.

  3. The involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects.

    LENUS (Irish Health Repository)

    Lyng, F M

    2006-04-01

    Much evidence now exists regarding radiation-induced bystander effects, but the mechanisms involved in the transduction of the signal are still unclear. The mitogen-activated protein kinase (MAPK) pathways have been linked to growth factor-mediated regulation of cellular events such as proliferation, senescence, differentiation and apoptosis. Activation of multiple MAPK pathways such as the ERK, JNK and p38 pathways have been shown to occur after exposure of cells to radiation and a variety of other toxic stresses. Previous studies have shown oxidative stress and calcium signaling to be important in radiation-induced bystander effects. The aim of the present study was to investigate MAPK signaling pathways in bystander cells exposed to irradiated cell conditioned medium (ICCM) and the role of oxidative metabolism and calcium signaling in the induction of bystander responses. Human keratinocytes (HPV-G cell line) were irradiated (0.005-5 Gy) using a cobalt-60 teletherapy unit. The medium was harvested 1 h postirradiation and transferred to recipient HPV-G cells. Phosphorylated forms of p38, JNK and ERK were studied by immunofluorescence 30 min-24 h after exposure to ICCM. Inhibitors of the ERK pathway (PD98059 and U0126), the JNK pathway (SP600125), and the p38 pathway (SB203580) were used to investigate whether bystander-induced cell death could be blocked. Cells were also incubated with ICCM in the presence of superoxide dismutase, catalase, EGTA, verapamil, nifedipine and thapsigargin to investigate whether bystander effects could be inhibited because of the known effects on calcium homeostasis. Activated forms of JNK and ERK proteins were observed after exposure to ICCM. Inhibition of the ERK pathway appeared to increase bystander-induced apoptosis, while inhibition of the JNK pathway appeared to decrease apoptosis. In addition, reactive oxygen species, such as superoxide and hydrogen peroxide, and calcium signaling were found to be important modulators of

  4. Fisetin provides antidepressant effects by activating the tropomyosin receptor kinase B signal pathway in mice.

    Science.gov (United States)

    Wang, Yamin; Wang, Bin; Lu, Jiaqi; Shi, Haixia; Gong, Siyi; Wang, Yufan; Hamdy, Ronald C; Chua, Balvin H L; Yang, Lingli; Xu, Xingshun

    2017-12-01

    Depression has been associated with a low-grade chronic inflammatory state, suggesting a potential therapeutic role for anti-inflammatory agents. Fisetin is a naturally occurring flavonoid in strawberries that has anti-inflammatory activities, but whether fisetin has antidepressant effects is unknown. In this study, we exposed mice to spatial restraint for 2 weeks with or without treatment with fisetin. Immobility time in the forced swimming and tail suspension test after this restraint increased in the untreated group, but this increase did not occur in the fisetin group. We administered fisetin to Abelson helper integration site-1 (Ahi1) knockout mice, which have depressive phenotypes. We found that fisetin attenuated the depressive phenotype of these Ahi1 knockout mice. We further investigated the potential mechanism of fisetin's antidepressant effects. Because TrkB is a critical signaling pathway in the mechanisms of depression, we examined whether phosphorylated TrkB was involved in the antidepressant effects of fisetin. We found that fisetin increased phosphorylated TrkB level without altering total TrkB; this increase was attenuated by K252a, a specific TrkB inhibitor. Taken together, our results demonstrated that fisetin may have therapeutic potential for treating depression and that this antidepressant effect may be mediated by the activation of the TrkB signaling pathway. © 2017 International Society for Neurochemistry.

  5. Characterization of the Antioxidant Effects of γ-Oryzanol: Involvement of the Nrf2 Pathway

    Directory of Open Access Journals (Sweden)

    W. Rungratanawanich

    2018-01-01

    Full Text Available γ-Oryzanol (ORY is well known for its antioxidant potential. However, the mechanism by which ORY exerts its antioxidant effect is still unclear. In this paper, the antioxidant properties of ORY were investigated for its potential effects as a reactive oxygen and nitrogen species (ROS/RNS scavenger and in activating antioxidant-promoting intracellular pathways utilizing the human embryonic kidney cells (HEK-293. The 24 h ORY exposure significantly prevented hydrogen peroxide- (H2O2- induced ROS/RNS production at 3 h, and this effect was sustained for at least 24 h. ORY pretreatment also enhanced the activity of antioxidant enzymes: superoxide dismutase (SOD and glutathione peroxidase (GPX. Interestingly, ORY induced the nuclear factor (erythroid-derived 2-like 2 (Nrf2 nuclear translocation and upregulation of Nrf2-dependent defensive genes such as NAD(PH quinone reductase (NQO1, heme oxygenase-1 (HO-1, and glutathione synthetase (GSS at mRNA and protein levels in both basal condition and after H2O2 insult. Thus, this study suggested an intriguing effect of ORY in modulating the Nrf2 pathway, which is also involved in regulating longevity as well as age-related diseases.

  6. Characterization of the Antioxidant Effects of γ-Oryzanol: Involvement of the Nrf2 Pathway.

    Science.gov (United States)

    Rungratanawanich, W; Abate, G; Serafini, M M; Guarienti, M; Catanzaro, M; Marziano, M; Memo, M; Lanni, C; Uberti, D

    2018-01-01

    γ -Oryzanol (ORY) is well known for its antioxidant potential. However, the mechanism by which ORY exerts its antioxidant effect is still unclear. In this paper, the antioxidant properties of ORY were investigated for its potential effects as a reactive oxygen and nitrogen species (ROS/RNS) scavenger and in activating antioxidant-promoting intracellular pathways utilizing the human embryonic kidney cells (HEK-293). The 24 h ORY exposure significantly prevented hydrogen peroxide- (H 2 O 2 -) induced ROS/RNS production at 3 h, and this effect was sustained for at least 24 h. ORY pretreatment also enhanced the activity of antioxidant enzymes: superoxide dismutase (SOD) and glutathione peroxidase (GPX). Interestingly, ORY induced the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation and upregulation of Nrf2-dependent defensive genes such as NAD(P)H quinone reductase (NQO1), heme oxygenase-1 (HO-1), and glutathione synthetase (GSS) at mRNA and protein levels in both basal condition and after H 2 O 2 insult. Thus, this study suggested an intriguing effect of ORY in modulating the Nrf2 pathway, which is also involved in regulating longevity as well as age-related diseases.

  7. Radiogenic health effects: communicating risks to the general public

    International Nuclear Information System (INIS)

    Strzelczyk, Jadwiga

    1999-01-01

    Harmful effects of prolonged radiation exposures were recognized early on following the discovery of X-rays by W.C. Roentgen in 1895. The type and severity of radiogenic effects are functions of a number of factors, radiation quality and quantity, chemical toxicity, and radiosensitivity of irradiated tissues being the most significant ones. Currently, there are several human registries for radiogenic cancers. Atomic bomb and nuclear test survivors, and populations exposed to medical irradiation constitute the largest study cohorts. Two general types of radiogenic effects have emerged from these registries: prompt and delayed. While the effects of acute exposures are very well documented, investigations of the effects of low-level exposures require the use of mathematical models. Communicating the risks of lower-level chronic radiation exposures to the general public remains a challenging task. The most effective approaches include clear interpretation and placing radiation risks in perspective: risks versus benefits, and comparisons with risks carried by common activities in which we all engage. (author)

  8. Polymer-inorganic hybrid proton conductive membranes: Effect of the interfacial transfer pathways

    International Nuclear Information System (INIS)

    Chen, Pingping; Hao, Lie; Wu, Wenjia; Li, Yifan; Wang, Jingtao

    2016-01-01

    Highlights: • A series of hybrid membranes are prepared using fillers with different structures. • The fillers (0-D, 1-D, and 2-D) are sulfonated to ensure close surface component. • The effect of filler’s structure on microstructure of hydrid membrane is explored. • For single-kind filler series, 2-D filler has the strongest conduction promotion. • The synergy effect of different kinds of fillers is systematacially investigated. - Abstract: For hybrid membrane, the polymer-inorganic interface along filler surface can be facilely created to be distinctive and controllable pathway for mass transfer. Herein, three kinds of fillers are used as inorganic additives including zero-dimensional silica (0-D, SiO_2), one-dimensional halloysite nanotube (1-D, HNT), and two-dimensional graphene oxide (2-D, GO), which are functionalized by sulfonated polymer layer to ensure close surface component. Then the fillers are incorporated into two types of polymer matrixes (phase-separated sulfonated poly(ether ether ketone) and non-phase-separated chitosan) to prepare three series of hybrid membranes with single-kind filler, double-kinds fillers, or triple-kinds fillers, respectively. The microstructures, physicochemical properties, and proton conduction properties (under hydrated and anhydrous conditions) of the membranes are extensively investigated. It is found that (i) for the single-kind filler-filled membranes, 2-D filler has the strongest promotion ability for proton conductivity of membrane due to the constructed wide and long-range pathways for proton transfer; (ii) while for the hybrid membranes with double-kinds fillers, instead of synergistic promotion effect, the fillers cause more tortuous transfer pathways within membranes and then decrease proton conductivity; (iii) the hybrid membranes with triple-kinds fillers exhibit similar behavior but a little higher conductivity than the membranes with double-kinds fillers.

  9. Strategy Implementation Style and Public Service Effectiveness, Efficiency, and Equity

    Directory of Open Access Journals (Sweden)

    Rhys Andrews

    2017-02-01

    Full Text Available Strategic decision-making theories suggest that organizations that combine rational and incremental strategy implementation styles are likely to perform better than those that emphasize a single style. To assess whether these arguments apply to the public sector; we explore the strategy implementation style and perceived service effectiveness, efficiency and equity of Turkish municipal government departments. Using fuzzy cluster analysis, we identify four distinctive though inter-related styles of strategy implementation in our sample organizations: logical-incremental; mostly rational; mostly incremental; and no clear approach. A logical-incremental and mostly rational style of implementation are associated with better effectiveness, efficiency and equity; with the absence of an implementation style associated with worse performance. Theoretical and practical implications are discussed.

  10. Effect of CAR activation on selected metabolic pathways in normal and hyperlipidemic mouse livers.

    Science.gov (United States)

    Rezen, Tadeja; Tamasi, Viola; Lövgren-Sandblom, Anita; Björkhem, Ingemar; Meyer, Urs A; Rozman, Damjana

    2009-08-19

    Detoxification in the liver involves activation of nuclear receptors, such as the constitutive androstane receptor (CAR), which regulate downstream genes of xenobiotic metabolism. Frequently, the metabolism of endobiotics is also modulated, resulting in potentially harmful effects. We therefore used 1,4-Bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) to study the effect of CAR activation on mouse hepatic transcriptome and lipid metabolome under conditions of diet-induced hyperlipidemia. Using gene expression profiling with a dedicated microarray, we show that xenobiotic metabolism, PPARalpha and adipocytokine signaling, and steroid synthesis are the pathways most affected by TCPOBOP in normal and hyperlipidemic mice. TCPOBOP-induced CAR activation prevented the increased hepatic and serum cholesterol caused by feeding mice a diet containing 1% cholesterol. We show that this is due to increased bile acid metabolism and up-regulated removal of LDL, even though TCPOBOP increased cholesterol synthesis under conditions of hyperlipidemia. Up-regulation of cholesterol synthesis was not accompanied by an increase in mature SREBP2 protein. As determined by studies in CAR -/- mice, up-regulation of cholesterol synthesis is however CAR-dependent; and no obvious CAR binding sites were detected in promoters of cholesterogenic genes. TCPOBOP also affected serum glucose and triglyceride levels and other metabolic processes in the liver, irrespective of the diet. Our data show that CAR activation modulates hepatic metabolism by lowering cholesterol and glucose levels, through effects on PPARalpha and adiponectin signaling pathways, and by compromising liver adaptations to hyperlipidemia.

  11. Affect labeling enhances exposure effectiveness for public speaking anxiety.

    Science.gov (United States)

    Niles, Andrea N; Craske, Michelle G; Lieberman, Matthew D; Hur, Christopher

    2015-05-01

    Exposure is an effective treatment for anxiety but many patients do not respond fully. Affect labeling (labeling emotional experience) attenuates emotional responding. The current project examined whether affect labeling enhances exposure effectiveness in participants with public speaking anxiety. Participants were randomized to exposure with or without affect labeling. Physiological arousal and self-reported fear were assessed before and after exposure and compared between groups. Consistent with hypotheses, participants assigned to Affect Labeling, especially those who used more labels during exposure, showed greater reduction in physiological activation than Control participants. No effect was found for self-report measures. Also, greater emotion regulation deficits at baseline predicted more benefit in physiological arousal from exposure combined with affect labeling than exposure alone. The current research provides evidence that behavioral strategies that target prefrontal-amygdala circuitry can improve treatment effectiveness for anxiety and these effects are particularly pronounced for patients with the greatest deficits in emotion regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Methylmercury causes neuronal cell death through the suppression of the TrkA pathway: In vitro and in vivo effects of TrkA pathway activators

    Energy Technology Data Exchange (ETDEWEB)

    Fujimura, Masatake, E-mail: fujimura@nimd.go.jp [Department of Basic Medical Sciences, National Institute for Minamata Disease, Kumamoto (Japan); Usuki, Fusako [Department of Clinical Medicine, National Institute for Minamata Disease, Kumamoto (Japan)

    2015-02-01

    Methylmercury (MeHg) is an environmental toxin which induces cell death specific for the nervous systems. Here we show that MeHg causes neuronal cell death through the suppression of the tropomyosin receptor kinase A (TrkA) pathway, and that compounds activating the TrkA pathway prevent MeHg-induced nerve damage in vitro and in vivo. We first investigated the mechanism of MeHg-induced neurotoxicity in differentiating neurons using PC12 cells. Exposure to 100 nM MeHg for 1 day induced apoptosis in differentiating PC12 cells. Further, MeHg-induced apoptosis was preceded by inhibition of neurite extension, as determined by ELISA analyses of the neurite-specific protein neurofilament triplet H protein (NF-H). To determine the mechanism of MeHg-induced apoptosis, we evaluated the effects of MeHg on the TrkA pathway, which is known to regulate neuronal differentiation and viability. Western blot analysis demonstrated that, like the TrkA phosphorylation inhibitor K252a, MeHg inhibited phosphorylation of TrkA and its downstream effectors. Furthermore, GM1 ganglioside and its analog MCC-257, which enhance TrkA phosphorylation, overcame the effect of MeHg in neurons, supporting the involvement of the TrkA pathway in MeHg-induced nerve damage. Finally, we demonstrated that MCC-257 rescued the clinical sign and pathological changes in MeHg-exposed rats. These findings indicate that MeHg-induced apoptosis in neuron is triggered by inhibition of the TrkA pathway, and that GM1 ganglioside and MCC-257 effectively prevent MeHg-induced nerve damage. - Highlights: • Exposure to 100 nM MeHg for 1 day induced apoptosis in differentiating PC12 cells. • Inhibition of neurite extension was involved in MeHg-induced apoptosis. • Like the TrkA phosphorylation inhibitor, MeHg inhibited phosphorylation of TrkA. • GM1 ganglioside and its analog effectively prevented MeHg-induced nerve damage.

  13. Effect of LIPUS on inflammatory factors, cell apoptosis and integrin signaling pathway in osteoarthritis animal models

    Directory of Open Access Journals (Sweden)

    Li-Cai Zhang

    2017-05-01

    Full Text Available Objective: To study the effect of low-intensity pulsed ultrasound (LIPUS on inflammatory factors, cell apoptosis and integrin signaling pathway in osteoarthritis animal models. Methods: Male New Zealand white rabbits were selected as the experimental animals and randomly divided into sham group, osteoarthritis model group (OA group and LIPUS intervention group (LIPUS group, animal models with osteoarthritis in hind limb knee joint were established and then given LIPUS intervention. 6 weeks after the intervention, the articular cartilage was separated to detect the expression of inflammatory factors, cell apoptosis molecules and integrin signaling pathway molecules. Results: OPN, NO, IL-1β, TNF-α, Fas, FasL, LC3-II, Beclin-1, Integrinβ1, FAK, ERK1/2, JNK, p38MAPK, MMP-1 and MMP-3 protein expression in articular cartilage of OA group were significantly higher than those of Sham group while Col-I and Col-II protein expression were significantly lower than those of Sham group; OPN, NO, IL-1β, TNF-α, Fas, FasL, LC3-II, Beclin-1, Integrinβ1, FAK, ERK1/2, JNK, p38MAPK, MMP-1 and MMP-3 protein expression in articular cartilage of LIPUS group were significantly lower than those of OA group while Col-I and Col-II protein expression were significantly higher than those of OA group. Conclusion: LIPUS has inhibiting effect on the inflammation, apoptosis and integrin signaling pathway in articular cartilage of osteoarthritis animal models, and it can promote the repair of articular cartilage.

  14. Oxidative stress suppresses the cellular bioenergetic effect of the 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway

    International Nuclear Information System (INIS)

    Módis, Katalin; Asimakopoulou, Antonia; Coletta, Ciro; Papapetropoulos, Andreas; Szabo, Csaba

    2013-01-01

    Highlights: •Oxidative stress impairs 3-MST-derived H 2 S production in isolated enzyme and in isolated mitochondria. •This impairs the stimulatory bioenergetic effects of H 2 S in hepatocytes. •This has implications for the pathophysiology of diseases with oxidative stress. -- Abstract: Recent data show that lower concentrations of hydrogen sulfide (H 2 S), as well as endogenous, intramitochondrial production of H 2 S by the 3-mercaptopyruvate (3-MP)/3-mercaptopyruvate sulfurtransferase (3-MST) pathway serves as an electron donor and inorganic source of energy to support mitochondrial electron transport and ATP generation in mammalian cells by donating electrons to Complex II. The aim of our study was to investigate the role of oxidative stress on the activity of the 3-MP/3-MST/H 2 S pathway in vitro. Hydrogen peroxide (H 2 O 2 , 100–500 μM) caused a concentration-dependent decrease in the activity of recombinant mouse 3-MST enzyme. In mitochondria isolated from murine hepatoma cells, H 2 O 2 (50–500 μM) caused a concentration-dependent decrease in production of H 2 S from 3-MP. In cultured murine hepatoma cells H 2 O 2 , (3–100 μM), did not result in overall cytotoxicity, but caused a partial decrease in basal oxygen consumption and respiratory reserve rapacity. The positive bioenergetic effect of 3-MP (100–300 nM) was completely abolished by pre-treatment of the cells with H 2 O 2 (50 μM). The current findings demonstrate that oxidative stress inhibits 3-MST activity and interferes with the positive bioenergetic role of the 3-MP/3-MST/H 2 S pathway. These findings may have implications for the pathophysiology of various conditions associated with increased oxidative stress, such as various forms of critical illness, cardiovascular diseases, diabetes or physiological aging

  15. Cost-effectiveness analysis of a postoperative clinical care pathway in head and neck surgery with microvascular reconstruction.

    Science.gov (United States)

    Dautremont, Jonathan F; Rudmik, Luke R; Yeung, Justin; Asante, Tiffany; Nakoneshny, Steve C; Hoy, Monica; Lui, Amanda; Chandarana, Shamir P; Matthews, Thomas W; Schrag, Christiaan; Dort, Joseph C

    2013-12-19

    The objective of this study is to evaluate the cost-effectiveness of a postoperative clinical care pathway for patients undergoing major head and neck oncologic surgery with microvascular reconstruction. This is a comparative trial of a prospective treatment group managed on a postoperative clinical care pathway and a historical group managed prior to pathway implementation. Effectiveness outcomes evaluated were total hospital days, return to OR, readmission to ICU and rate of pulmonary complications. Costing perspective was from the government payer. 118 patients were included in the study. All outcomes demonstrated that the postoperative pathway group was both more effective and less costly, and is therefore a dominant clinical intervention. The overall mean pre- and post-pathway costs are $22,733 and $16,564 per patient, respectively. The incremental cost reduction associated with the postoperative pathway was $6,169 per patient. Implementing the postoperative clinical care pathway in patients undergoing head and neck oncologic surgery with reconstruction resulted in improved clinical outcomes and reduced costs.

  16. Designing effective incentives for energy conservation in the public sector

    Science.gov (United States)

    Drezner, Jeffrey Alan

    Understanding why government officials behave in certain ways under particular circumstances is an important theme in political science. This research explores the design of policies and incentives targeted at public sector officials, in particular the use of market based policy tools in a non-market environment, and the influence of that organizational environment on the effectiveness of the policy. The research examines the case of Department of Defense (DoD) facility energy management. DoD energy policy includes a provision for the retention of savings generated by conservation activities: two-thirds of the savings is retained at the installation generating the savings, half to used for further investment in energy conservation, and half to be used for general morale, welfare, and recreation activities. This policy creates a financial incentive for installation energy managers to establish higher quality and more active conservation programs. A formal written survey of installation energy managers within DoD was conducted, providing data to test hypotheses regarding policy effectiveness and factors affecting policy implementation. Additionally, two detailed implementation case studies were conducted in order to gain further insights. Results suggest that policy design needs to account for the environment within which the policy will be implemented, particularly organizational culture and standard operating procedures. The retention of savings policy failed to achieve its intended outcome---retention of savings for re-investment in energy conservation---because the role required of the financial management community was outside its normal mode of operation and interests and the budget process for allocating resources did not include a mechanism for retention of savings. The policy design did not adequately address these start-up barriers to implementation. This analysis has shown that in order for retention of savings, or similar policies based on market

  17. Modulation of low dose radiation effect on pentose phosphate pathway enzymes by B-multivitamin deficiency

    International Nuclear Information System (INIS)

    Zimatkina, T.I.; Lashak, L.K.; Moiseenok, A.G.

    1997-01-01

    Blood, liver, thymus and spleen of albino rats injected subcutaneously with antivitamins (othythiamine and methotrexate) and subjected to prolonger γ-irradiation in the overall dose of 0.75 Gy were assayed for transketolase and glucose-6-phosphate dehydrogenase after 12h, 1, 2, 5 and 40 days from the last radiation dose. High transketolase sensitivity was found both to radiation (activation) and the combined effects of vitamin deficiency and radiation (potentiation of antivitamin inhibitory action) in all the tissues studied. The activity of glucose-6-phosphate dehydrogenase was little changed under the given experimental manipulations, but the combined effect of the factors considerably inhibited the enzyme activities in the organs of the immune system. Consequently, in B-multivitamin deficiency the effect of low radiation doses was subjected to a considerable modulation resulting in profound inhibition of the oxidation and nonoxidative branches of the pentose phosphate pathway. (author). 9 refs, 2 tabs

  18. The effects of teacher fidelity of implementation of pathways to health on student outcomes.

    Science.gov (United States)

    Little, Melissa A; Riggs, Nathaniel R; Shin, Hee-Sung; Tate, Eleanor B; Pentz, Mary Ann

    2015-03-01

    Previous research has demonstrated the importance of ensuring that programs are implemented as intended by program developers in order to achieve desired program effects. The current study examined implementation fidelity of Pathways to Health (Pathways), a newly developed obesity prevention program for fourth- through sixth-grade children. We explored the associations between self-reported and observed implementation fidelity scores and whether implementation fidelity differed across the first 2 years of program implementation. Additionally, we examined whether implementation fidelity affected program outcomes and whether teacher beliefs were associated with implementation fidelity. The program was better received, and implementation fidelity had more effects on program outcomes in fifth grade than in fourth grade. Findings suggest that implementation in school-based obesity programs may affect junk food intake and intentions to eat healthfully and exercise. School support was associated with implementation fidelity, suggesting that prevention programs may benefit from including a component that boosts school-wide support. © The Author(s) 2013.

  19. Degradation of ibuprofen by hydrodynamic cavitation: Reaction pathways and effect of operational parameters.

    Science.gov (United States)

    Musmarra, Dino; Prisciandaro, Marina; Capocelli, Mauro; Karatza, Despina; Iovino, Pasquale; Canzano, Silvana; Lancia, Amedeo

    2016-03-01

    Ibuprofen (IBP) is an anti-inflammatory drug whose residues can be found worldwide in natural water bodies resulting in harmful effects to aquatic species even at low concentrations. This paper deals with the degradation of IBP in water by hydrodynamic cavitation in a convergent-divergent nozzle. Over 60% of ibuprofen was degraded in 60 min with an electrical energy per order (EEO) of 10.77 kWh m(-3) at an initial concentration of 200 μg L(-1) and a relative inlet pressure pin=0.35 MPa. Five intermediates generated from different hydroxylation reactions were identified; the potential mechanisms of degradation were sketched and discussed. The reaction pathways recognized are in line with the relevant literature, both experimental and theoretical. By varying the pressure upstream the constriction, different degradation rates were observed. This effect was discussed according to a numerical simulation of the hydroxyl radical production identifying a clear correspondence between the maximum kinetic constant kOH and the maximum calculated OH production. Furthermore, in the investigated experimental conditions, the pH parameter was found not to affect the extent of degradation; this peculiar feature agrees with a recently published kinetic insight and has been explained in the light of the intermediates of the different reaction pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Effect of ethanol on innate antiviral pathways and HCV replication in human liver cells

    Directory of Open Access Journals (Sweden)

    Fausto Nelson

    2005-12-01

    Full Text Available Abstract Alcohol abuse reduces response rates to IFN therapy in patients with chronic hepatitis C. To model the molecular mechanisms behind this phenotype, we characterized the effects of ethanol on Jak-Stat and MAPK pathways in Huh7 human hepatoma cells, in HCV replicon cell lines, and in primary human hepatocytes. High physiological concentrations of acute ethanol activated the Jak-Stat and p38 MAPK pathways and inhibited HCV replication in several independent replicon cell lines. Moreover, acute ethanol induced Stat1 serine phosphorylation, which was partially mediated by the p38 MAPK pathway. In contrast, when combined with exogenously applied IFN-α, ethanol inhibited the antiviral actions of IFN against HCV replication, involving inhibition of IFN-induced Stat1 tyrosine phosphorylation. These effects of alcohol occurred independently of i alcohol metabolism via ADH and CYP2E1, and ii cytotoxic or cytostatic effects of ethanol. In this model system, ethanol directly perturbs the Jak-Stat pathway, and HCV replication. Infection with Hepatitis C virus is a significant cause of morbidity and mortality throughout the world. With a propensity to progress to chronic infection, approximately 70% of patients with chronic viremia develop histological evidence of chronic liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The situation is even more dire for patients who abuse ethanol, where the risk of developing end stage liver disease is significantly higher as compared to HCV patients who do not drink 12. Recombinant interferon alpha (IFN-α therapy produces sustained responses (ie clearance of viremia in 8–12% of patients with chronic hepatitis C 3. Significant improvements in response rates can be achieved with IFN plus ribavirin combination 456 and pegylated IFN plus ribavirin 78 therapies. However, over 50% of chronically infected patients still do not clear viremia. Moreover, HCV-infected patients who abuse

  1. What Constrains Effective Public Financial Management in African ...

    African Journals Online (AJOL)

    While the management of the area of public finance is highly legislated, the waste with which these resources slip through the public coffers remains a paradox. The purpose of this article is to examine the five self-reinforcing variables that are mostly fingered for this dilemma. These are: (1) public finance as a political ...

  2. Effect of psychological stress on the L-arginine-nitric oxide pathway and semen quality

    Directory of Open Access Journals (Sweden)

    S. Eskiocak

    2006-05-01

    Full Text Available It has been reported that mental stress causes abnormality of spermiogram parameters. We investigated the effect of psychological stress on the L-arginine-nitric oxide (NO pathway. Semen samples were collected from 29 healthy fourth semester medical students just before (stress and 3 months after (non-stress the final examinations. Psychological stress was measured by the State Anxiety Inventory questionnaire. After standard semen analysis, arginase activity and NO concentration were measured spectrophotometrically in the seminal plasma. Measurements were made in duplicate. During the stress period, sperm concentration (41.28 ± 3.70 vs 77.62 ± 7.13 x 10(6/mL, rapid progressive motility of spermatozoa (8.79 ± 1.66 vs 20.86 ± 1.63% and seminal plasma arginase activity (0.12 ± 0.01 vs 0.22 ± 0.01 U/mL were significantly lower than in the non-stress situation, whereas seminal plasma NO (17.28 ± 0.56 vs 10.02 ± 0.49 µmol/L was higher compared to the non-stress period (P < 0.001 for all. During stress there was a negative correlation between NO concentration and sperm concentration, the percentage of rapid progressive motility and arginase activity (r = -0.622, P < 0.01; r = -0.425, P < 0.05 and r = -0.445, P < 0.05, respectively. These results indicate that psychological stress causes an increase of NO level and a decrease of arginase activity in the L-arginine-NO pathway. Furthermore, poor sperm quality may be due to excessive production of NO under psychological stress. In the light of these results, we suggest that the arginine-NO pathway, together with arginase and NO synthase, are involved in semen quality under stress conditions.

  3. Pravastatin Effects on Placental Prosurvival Molecular Pathways in a Mouse Model of Preeclampsia.

    Science.gov (United States)

    Saad, Antonio F; Diken, Zaid M; Kechichian, Talar B; Clark, Shannon M; Olson, Gayle L; Saade, George R; Costantine, Maged M

    2016-11-01

    Using an animal model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1), we previously showed that pravastatin prevents the development of a preeclampsia phenotype. Our objective is to determine whether pravastatin treatment may be explained by its effects on apoptotic/survival pathways in the placenta. Pregnant CD1 mice at day 8 of gestation (length of gestation 19 days) were randomly allocated to injection via tail vein with either adenovirus carrying sFlt-1 or adenovirus carrying the murine immunoglobulin G2α Fc fragment (mFc virus control group). Mice from the sFlt group were randomly assigned to receive pravastatin (5 mg/kg/d) in their drinking water from day 9 until killing (sFlt-1 + Pravastatin) or water (sFlt-1). The mFc control received water only. Mice were killed on day 18, and the placentas were collected. Protein mitogen-activated protein kinase (MAPK) pathway substrates were assayed using Bioplex Multiplex Immunoassay (Bio-Rad, Hercules, California). Data are reported as mean  ±  standard error of the mean or median (interquartile range) when appropriate. One-way analysis of variance followed by post hoc analysis was performed. Two-sided P value preeclampsia phenotype may be mediated through pleiotropic mechanisms involving a prosurvival/ antiapoptotic MAPK pathway in the placenta. Our results further support continued research in the role for statins in the prevention of preeclampsia. © The Author(s) 2016.

  4. Ethanol-metabolizing pathways in deermice. Estimation of flux calculated from isotope effects

    International Nuclear Information System (INIS)

    Alderman, J.; Takagi, T.; Lieber, C.S.

    1987-01-01

    The apparent deuterium isotope effects on Vmax/Km (D(V/K] of ethanol oxidation in two deermouse strains (one having and one lacking hepatic alcohol dehydrogenase (ADH] were used to calculate flux through the ADH, microsomal ethanol-oxidizing system (MEOS), and catalase pathways. In vitro, D(V/K) values were 3.22 for ADH, 1.13 for MEOS, and 1.83 for catalase under physiological conditions of pH, temperature, and ionic strength. In vivo, in deermice lacking ADH (ADH-), D(V/K) was 1.20 +/- 0.09 (mean +/- S.E.) at 7.0 +/- 0.5 mM blood ethanol and 1.08 +/- 0.10 at 57.8 +/- 10.2 mM blood ethanol, consistent with ethanol oxidation principally by MEOS. Pretreatment of ADH- animals with the catalase inhibitor 3-amino-1,2,4-triazole did not significantly change D(V/K). ADH+ deermice exhibited D(V/K) values of 1.87 +/- 0.06 (untreated), 1.71 +/- 0.13 (pretreated with 3-amino-1,2,4-triazole), and 1.24 +/- 0.13 (after the ADH inhibitor, 4-methylpyrazole) at 5-7 mM blood ethanol levels. At elevated blood ethanol concentrations (58.1 +/- 2.4 mM), a D(V/K) of 1.37 +/- 0.21 was measured in the ADH+ strain. For measured D(V/K) values to accurately reflect pathway contributions, initial reaction conditions are essential. These were shown to exist by the following criteria: negligible fractional conversion of substrate to product and no measurable back reaction in deermice having a reversible enzyme (ADH). Thus, calculations from D(V/K) indicate that, even when ADH is present, non-ADH pathways (mostly MEOS) participate significantly in ethanol metabolism at all concentrations tested and play a major role at high levels

  5. Effect of secretory pathway gene overexpression on secretion of a fluorescent reporter protein in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Schalén, Martin; Anyaogu, Diana Chinyere; Hoof, Jakob Blæsbjerg

    2016-01-01

    roles in the process have been identified through transcriptomics. The assignment of function to these genes has been enabled in combination with gene deletion studies. In this work, 14 genes known to play a role in protein secretion in filamentous fungi were overexpressed in Aspergillus nidulans....... The background strain was a fluorescent reporter secreting mRFP. The overall effect of the overexpressions could thus be easily monitored through fluorescence measurements, while the effects on physiology were determined in batch cultivations and surface growth studies. Results: Fourteen protein secretion...... pathway related genes were overexpressed with a tet-ON promoter in the RFP-secreting reporter strain and macromorphology, physiology and protein secretion were monitored when the secretory genes were induced. Overexpression of several of the chosen genes was shown to cause anomalies on growth, micro...

  6. Effect of transcranial direct current stimulation on neuroplasticity in corticomotor pathways of the tongue muscles

    DEFF Research Database (Denmark)

    Kothari, Mohit; Stubbs, Peter William; Figlewski, Krystian

    2017-01-01

    To investigate effects of transcranial direct current stimulation (tDCS) on neuroplasticity in corticomotor pathways related to tongue muscles evoked by a training task using the Tongue Drive System (TDS). Using a cross-over design, 13 healthy participants completed two sessions of tDCS while...... performing 30 min of TDS training. Sessions were spaced at least 2 weeks apart and participants randomly received anodal and sham tDCS stimulation in the first session and the other condition in the second session. Single and paired pulse transcranial magnetic stimulation was used to elicit motor evoked...... potentials (MEPs) of the tongue at three time-points; before, immediately after and 30 min after training. Participant-based reports of fun, pain, fatigue and motivation, level of difficulty and effort were evaluated on numerical rating scales. There was no consistent significant effect of anodal and sham...

  7. Diffused and sustained inhibitory effects of intestinal electrical stimulation on intestinal motility mediated via sympathetic pathway.

    Science.gov (United States)

    Zhao, Xiaotuan; Yin, Jieyun; Wang, Lijie; Chen, Jiande D Z

    2014-06-01

    The aims were to investigate the energy-dose response effect of intestinal electrical stimulation (IES) on small bowel motility, to compare the effect of forward and backward IES, and to explore the possibility of using intermittent IES and mechanism of IES on intestinal motility. Five dogs implanted with a duodenal cannula and one pair of intestinal serosal electrodes were studied in five sessions: 1) energy-dose response study; 2) forward IES; 3) backward IES; 4) intermittent IES vs. continuous IES; 5) administration of guanethidine. The contractile activity and tonic pressure of the small intestine were recorded. The duration of sustained effect after turning off IES was manually calculated. 1) IES with long pulse energy dose dependently inhibited contractile activity and tonic pressure of the small intestine (p intestine depended on the energy of IES delivered (p intestine. 5) Guanethidine blocked the inhibitory effect of IES on intestinal motility. IES with long pulses inhibits small intestinal motility; the effect is energy-dose dependent, diffused, and sustained. Intermittent IES has the same efficacy as the continuous IES in inhibiting small intestinal motility. Forward and backward IES have similar inhibitory effects on small bowel motility. This IES-induced inhibitory effect is mediated via the sympathetic pathway. © 2013 International Neuromodulation Society.

  8. The Effect of a High School Speech Course on Public Speaking Anxiety for Students in a College-Level Public Speaking Class

    Science.gov (United States)

    Johnson, Karen Hill

    2012-01-01

    Literature suggested public speaking is American's most feared activity. Additionally, the public speaking curriculum was removed from the K-12 school system after 2001. This study aimed to examine the effect of previous public speaking instruction, public speaking extra-curricular activity, gender, and self-esteem on public speaking anxiety…

  9. Industrial PM2.5 cause pulmonary adverse effect through RhoA/ROCK pathway.

    Science.gov (United States)

    Yan, Junyan; Lai, Chia-Hsiang; Lung, Shih-Chun Candice; Chen, Chongjun; Wang, Wen-Cheng; Huang, Pin-I; Lin, Chia-Hua

    2017-12-01

    According to the Chinese Ministry of Health, industrial pollution-induced health impacts have been the leading cause of death in China. While industrial fine particulate matter (PM 2.5 ) is associated with adverse health effects, the major action mechanisms of different compositions of PM 2.5 are currently unclear. In this study, we treated normal human lung epithelial BEAS-2B cells with industrial organic and water-soluble PM 2.5 extracts under daily alveolar deposition dose to elucidate the molecular mechanisms underlying adverse pulmonary effects induced by PM 2.5 , including oxidative damage, inflammatory response, lung epithelial barrier dysfunction, and the recruitment of macrophages. We found that water-soluble PM 2.5 extracts caused more severe cytotoxic effects on BEAS-2B cells compared with that of organic extracts. Both organic and water-soluble PM 2.5 extracts induced activation of the RhoA/ROCK pathway. Inflammatory response, epithelial barrier dysfunction, and the activation of NF-кB caused by both PM 2.5 extracts were attenuated by ROCK inhibitor Y-27632. This indicated that both PM 2.5 extracts could cause damage to epithelial cells through RhoA/ROCK-dependent NF-кB activation. Furthermore, the upregulation of macrophage adhesion induced by both PM 2.5 extracts was also attenuated by Y-27632 in a co-culture model of macrophages and the epithelial cells. Therefore, our results support that industrial PM 2.5 extracts-induced activation of the RhoA/ROCK-dependent NF-кB pathway induces pulmonary adverse effect. Thus, pharmacological inhibition of ROCK activation might have therapeutic potential in preventing lung disease associated with PM 2.5 . Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effects of CD44 Ligation on Signaling and Metabolic Pathways in Acute Myeloid Leukemia

    KAUST Repository

    Madhoun, Nour Y.

    2017-04-01

    Acute myeloid leukemia (AML) is characterized by a blockage in the differentiation of myeloid cells at different stages. CD44-ligation using anti-CD44 monoclonal antibodies (mAbs) has been shown to reverse the blockage of differentiation and to inhibit the proliferation of blasts in most AML-subtypes. However, the molecular mechanisms underlying this property have not been fully elucidated. Here, we sought to I) analyze the effects of anti-CD44 mAbs on downstream signaling pathways, including the ERK1/2 (extracellular signal-regulated kinase 1 and 2) and mTOR (mammalian target of rapamycin) pathways and II) use state-of-the-art Nuclear Magnetic Resonance (NMR) technology to determine the global metabolic changes during differentiation induction of AML cells using anti-CD44 mAbs and other two previously reported differentiation agents. In the first objective (Chapter 4), our studies provide evidence that CD44-ligation with specific mAbs in AML cells induced an increase in ERK1/2 phosphorylation. The use of the MEK inhibitor (U0126) significantly inhibited the CD44-induced differentiation of HL60 cells, suggesting that ERK1/2 is critical for the CD44-triggered differentiation in AML. In addition, this was accompanied by a marked decrease in the phosphorylation of the mTORC1 and mTORC2 complexes, which are strongly correlated with the inhibition of the PI3K/Akt pathway. In the second objective (Chapter 5), 1H NMR experiments demonstrated that considerable changes in the metabolic profiles of HL60 cells were induced in response to each differentiation agent. These most notable metabolites that significantly changed upon CD44 ligation were involved in the tricarboxylic acid (TCA) cycle and glycolysis such as, succinate, fumarate and lactate. Therefore, we sought to analyze the mechanisms underlying their alterations. Our results revealed that anti-CD44 mAbs treatment induced upregulation in fumarate hydratase (FH) expression and its activity which was accompanied by a

  11. Investigating the expression, effect and tumorigenic pathway of PADI2 in tumors

    Directory of Open Access Journals (Sweden)

    Guo W

    2017-03-01

    Full Text Available Wei Guo,1,2,* Yabing Zheng,2,* Bing Xu,1 Fang Ma,1 Chang Li,3 Xiaoqian Zhang,4 Yao Wang,1 Xiaotian Chang1 1Medical Research Center, Shandong Provincial Qianfoshan Hospital, 2Obstetrical Department, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 3Pathology Department, Tengzhou Central People’s Hospital, Tengzhou, 4Clinical Laboratory, PKU Care Luzhong Hospital, Zibo, Shandong, People’s Republic of China *These authors contributed equally to this work Background: Peptidylarginine deiminase (PAD catalyzes the conversion of arginine residues to citrulline residues, termed citrullination. Recent studies have suggested that PAD isoform 2 (PADI2 plays an important role in tumors, although its tumorigenic effect and mechanism are largely unknown. Materials and methods: Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA were used to investigate the expression level of PADI2 in various tumor tissues and patient blood samples, respectively. MNK-45 and Bel-7402 tumor cell lines originating from gastric and liver tumors, respectively, were treated with anti-PADI2 siRNA, and the subsequent cell proliferation, apoptosis and migration were observed. Polymerase chain reaction (PCR arrays, including Cancer PathwayFinder, Oncogenes and Tumor Suppressor Genes, p53 Signaling Pathway, Signal Transduction Pathway and Tumor Metastasis PCR arrays, were used to investigate the tumorigenic pathway of PADI2 in the siRNA-treated tumor cells. This analysis was verified by real-time PCR. Results: Immunohistochemistry detected significantly increased expression of PADI2 in invasive breast ductal carcinoma, cervical squamous cell carcinoma, colon adenocarcinoma, liver hepatocellular carcinoma, lung cancer, ovarian serous papillary adenocarcinoma and papillary thyroid carcinoma samples. ELISA detected a twofold increase in PADI2 expression in the blood of 48.3% of patients with liver cancer, 38% of patients with cervical

  12. Pathway Distiller - multisource biological pathway consolidation.

    Science.gov (United States)

    Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

    2012-01-01

    One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

  13. [Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis].

    Science.gov (United States)

    Xiao, Ya-Ping; Zeng, Jie; Jiao, Lin-Na; Xu, Xiao-Yu

    2018-01-01

    The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/ β -catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/ β -catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification. Copyright© by the Chinese Pharmaceutical Association.

  14. Dietary flavonoid derivatives enhance chemotherapeutic effect by inhibiting the DNA damage response pathway

    International Nuclear Information System (INIS)

    Kuo, Ching-Ying; Zupkó, István; Chang, Fang-Rong; Hunyadi, Attila; Wu, Chin-Chung; Weng, Teng-Song; Wang, Hui-Chun

    2016-01-01

    Flavonoids are the most common group of polyphenolic compounds and abundant in dietary fruits and vegetables. Diet high in vegetables or dietary flavonoid supplements is associated with reduced mortality rate for patients with breast cancer. Many studies have been proposed for mechanisms linking flavonoids to improving chemotherapy efficacy in many types of cancers, but data on this issue is still limited. Herein, we report on a new mechanism through which dietary flavonoids inhibit DNA damage checkpoints and repair pathways. We found that dietary flavonoids could inhibit Chk1 phosphorylation and decrease clonogenic cell growth once breast cancer cells receive ultraviolet irradiation, cisplatin, or etoposide treatment. Since the ATR-Chk1 pathway mainly involves response to DNA replication stress, we propose that flavonoid derivatives reduce the side effect of chemotherapy by improving the sensitivity of cycling cells. Therefore, we propose that increasing intake of common dietary flavonoids is beneficial to breast cancer patients who are receiving DNA-damaging chemotherapy, such as cisplatin or etoposide-based therapy. - Highlights: • First report on inhibition of both DNA damage and repair by dietary flavonoids • Dietary flavonoids inhibit cisplatin- and UV-induced Chk1 phosphorylation. • Flavonoids combined with cisplatin or UV treatment show notable growth inhibition. • Promising treatment proposal for patients who are receiving adjuvant chemotherapy

  15. The effect of the size of fluorescent dextran on its endocytic pathway.

    Science.gov (United States)

    Li, Lei; Wan, Tao; Wan, Min; Liu, Bei; Cheng, Ran; Zhang, Rongying

    2015-05-01

    Fluorescent dextrans are commonly used as macropinocytic probes to study the properties of endocytic cargoes; however, the effect of the size of dextrans on endocytic mechanisms has not been carefully analyzed. By using chemical and siRNA inhibition of individual endocytic pathways, we evaluated the internalization of two commonly used dextrans, Dex10 (dextran 10 kDa) and Dex70 (dextran 70 kDa), in mammalian HeLa cells and Caenorhabditis elegans coelomocytes. We revealed that Dex70 enters these two cell types predominantly via clathrin- and dynamin-independent and amiloride-sensitive macropinocytosis process; Dex10, on the other hand, enters the two cell types through clathrin-/dynamin-dependent micropinocytosis in addition to macropinocytosis. In addition, although different-sized dextrans follow different endocytic processes, they share common post-endocytic events. Herein, though straightforward, our studies support that the size of nanomaterials could play a paramount role in their inclusion into endocytic vesicles and suggest that care should be taken while selecting endocytic pathway markers. Based on our results, we propose that Dex70 is a better probe for macropinocytosis, whereas Dex10 and smaller molecules are better for probing general fluid-phase endocytosis, which includes macropinocytic and micropinocytic processes. © 2015 International Federation for Cell Biology.

  16. Dietary flavonoid derivatives enhance chemotherapeutic effect by inhibiting the DNA damage response pathway

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Ching-Ying [Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Zupkó, István [Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös Utca 6, Szeged H-6720 (Hungary); Chang, Fang-Rong [Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hunyadi, Attila [Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Eötvös Utca 6, Szeged H-6720 (Hungary); Wu, Chin-Chung; Weng, Teng-Song [Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Wang, Hui-Chun, E-mail: wanghc@kmu.edu.tw [Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); PhD Program in Translational Medicine, College of Medicine and PhD Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Research Center for Natural Product and Drug Development, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Translational Research Center and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan (China); Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan (China); Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2016-11-15

    Flavonoids are the most common group of polyphenolic compounds and abundant in dietary fruits and vegetables. Diet high in vegetables or dietary flavonoid supplements is associated with reduced mortality rate for patients with breast cancer. Many studies have been proposed for mechanisms linking flavonoids to improving chemotherapy efficacy in many types of cancers, but data on this issue is still limited. Herein, we report on a new mechanism through which dietary flavonoids inhibit DNA damage checkpoints and repair pathways. We found that dietary flavonoids could inhibit Chk1 phosphorylation and decrease clonogenic cell growth once breast cancer cells receive ultraviolet irradiation, cisplatin, or etoposide treatment. Since the ATR-Chk1 pathway mainly involves response to DNA replication stress, we propose that flavonoid derivatives reduce the side effect of chemotherapy by improving the sensitivity of cycling cells. Therefore, we propose that increasing intake of common dietary flavonoids is beneficial to breast cancer patients who are receiving DNA-damaging chemotherapy, such as cisplatin or etoposide-based therapy. - Highlights: • First report on inhibition of both DNA damage and repair by dietary flavonoids • Dietary flavonoids inhibit cisplatin- and UV-induced Chk1 phosphorylation. • Flavonoids combined with cisplatin or UV treatment show notable growth inhibition. • Promising treatment proposal for patients who are receiving adjuvant chemotherapy.

  17. Effects of Methylphenidate on Resting-State Functional Connectivity of the Mesocorticolimbic Dopamine Pathways in Cocaine Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Volkow, Nora D.; Goldstein, Rita Z.

    2013-08-01

    Cocaine addiction is associated with altered resting-state functional connectivity among regions of the mesocorticolimbic dopamine pathways. Methylphenidate hydrochloride, an indirect dopamine agonist, normalizes task-related regional brain activity and associated behavior in cocaine users; however, the neural systems–level effects of methylphenidate in this population have not yet been described. To use resting-state functional magnetic resonance imaging to examine changes in mesocorticolimbic connectivity with methylphenidate and how connectivity of affected pathways relates to severity of cocaine addiction.

  18. Possible involvement of the JAK/STAT signaling pathway in N-acetylcysteine-mediated antidepressant-like effects

    OpenAIRE

    Al-Samhari, Marwa M; Al-Rasheed, Nouf M; Al-Rejaie, Salim; Al-Rasheed, Nawal M; Hasan, Iman H; Mahmoud, Ayman M; Dzimiri, Nduna

    2015-01-01

    Advances in depression research have targeted inflammation and oxidative stress to develop novel types of treatment. The JAK/STAT signaling pathway plays pivotal roles in immune and inflammatory responses. The present study was designed to investigate the effects of N-acetylcysteine, a putative precursor of the antioxidant glutathione, in an animal model of depression, with an emphasis on the JAK/STAT signaling pathway. Fluoxetine, a classical antidepressant drug was also under investigation....

  19. Stimulatory effect of repeated treatment with lipopolysaccharide on a key enzyme of the kynurenine pathway in both genders in rats

    Directory of Open Access Journals (Sweden)

    Csanova A.

    2016-09-01

    Full Text Available The neuroprotective or neurotoxic effects of the products of the kynurenine pathway of tryptophan metabolism highly depend on the action of kynurenine-3-monooxygenase (KMO. The present results show increased concentrations of the KMO in the plasma of rats repeatedly exposed to an immune challenge. Increased concentrations of this key enzyme are likely to cause a shift of kynurenine pathway towards enhanced production of neurotoxic metabolites.

  20. Signaling pathways underlying the antidepressant-like effect of inosine in mice.

    Science.gov (United States)

    Gonçalves, Filipe Marques; Neis, Vivian Binder; Rieger, Débora Kurrle; Lopes, Mark William; Heinrich, Isabella A; Costa, Ana Paula; Rodrigues, Ana Lúcia S; Kaster, Manuella P; Leal, Rodrigo Bainy

    2017-06-01

    Inosine is a purine nucleoside formed by the breakdown of adenosine that elicits an antidepressant-like effect in mice through activation of adenosine A 1 and A 2A receptors. However, the signaling pathways underlying this effect are largely unknown. To address this issue, the present study investigated the influence of extracellular-regulated protein kinase (ERK)1/2, Ca 2+ /calmoduline-dependent protein kinase (CaMKII), protein kinase A (PKA), phosphoinositide 3-kinase (PI3K)/Akt, and glycogen synthase kinase 3beta (GSK-3β) modulation in the antiimmobility effect of inosine in the tail suspension test (TST) in mice. In addition, we attempted to verify if inosine treatment was capable of altering the immunocontent and phosphorylation of the transcription factor cyclic adenosine monophosphatate (cAMP) response-binding element protein (CREB) in mouse prefrontal cortex and hippocampus. Intracerebroventricular administration of U0126 (5 μg/mouse, MEK1/2 inhibitor), KN-62 (1 μg/mouse, CaMKII inhibitor), H-89 (1 μg/mouse, PKA inhibitor), and wortmannin (0.1 μg/mouse, PI3K inhibitor) prevented the antiimmobility effect of inosine (10 mg/kg, intraperitoneal (i.p.)) in the TST. Also, administration of a sub-effective dose of inosine (0.1 mg/kg, i.p.) in combination with a sub-effective dose of AR-A014418 (0.001 μg/mouse, GSK-3β inhibitor) induced a synergic antidepressant-like effect. None of the treatments altered locomotor activity of mice. Moreover, 24 h after a single administration of inosine (10 mg/kg, i.p.), CREB phosphorylation was increased in the hippocampus. Our findings provided new evidence that the antidepressant-like effect of inosine in the TST involves the activation of PKA, PI3K/Akt, ERK1/2, and CaMKII and the inhibition of GSK-3β. These results contribute to the comprehension of the mechanisms underlying the purinergic system modulation and indicate the intracellular signaling pathways involved in the antidepressant-like effect of inosine

  1. Intercellular and intracellular signaling pathways mediating ionizing radiation-induced bystander effects

    International Nuclear Information System (INIS)

    Hamada, Nobuyuki; Hara, Takamitsu; Kobayashi, Yasuhiko; Matsumoto, Hideki

    2007-01-01

    A rapidly growing body of experimental evidence indicates that ionizing radiation induces biological effects in non-irradiated bystander cells that have received signals from adjacent or distant irradiated cells. This phenomenon, which has been termed the ionizing radiation-induced bystander effect, challenges the long-standing paradigm that radiation traversal through the nucleus of a cell is a prerequisite to elicit genetic damage or a biological response. Bystander effects have been observed in a number of experimental systems, and cells whose nucleus or cytoplasm is irradiated exert bystander responses. Bystander cells manifest a multitude of biological consequences, such as genetic and epigenetic changes, alterations in gene expression, activation of signal transduction pathways, and delayed effects in their progeny. Several mediating mechanisms have been proposed. These involve gap junction-mediated intercellular communication, secreted soluble factors, oxidative metabolism, plasma membrane-bound lipid rafts, and calcium fluxes. This paper reviews briefly the current knowledge of the bystander effect with a focus on proposed mechanisms. The potential benefit of bystander effects to cancer radiotherapy will also be discussed. (author)

  2. A cluster randomized trial to assess the effect of clinical pathways for patients with stroke: results of the clinical pathways for effective and appropriate care study

    Directory of Open Access Journals (Sweden)

    Panella Massimiliano

    2012-07-01

    Full Text Available Abstract Background Clinical pathways (CPs are used to improve the outcomes of acute stroke, but their use in stroke care is questionable, because the evidence on their effectiveness is still inconclusive. The objective of this study was to evaluate whether CPs improve the outcomes and the quality of care provided to patients after acute ischemic stroke. Methods This was a multicentre cluster-randomized trial, in which 14 hospitals were randomized to the CP arm or to the non intervention/usual care (UC arm. Healthcare workers in the CP arm received 3 days of training in quality improvement of CPs and in use of a standardized package including information on evidence-based key interventions and indicators. Healthcare workers in the usual-care arm followed their standard procedures. The teams in the CP arm developed their CPs over a 6-month period. The primary end point was mortality. Secondary end points were: use of diagnostic and therapeutic procedures, implementation of organized care, length of stay, re-admission and institutionalization rates after discharge, dependency levels, and complication rates. Results Compared with the patients in the UC arm, the patients in the CP arm had a significantly lower risk of mortality at 7 days (OR = 0.10; 95% CI 0.01 to 0.95 and significantly lower rates of adverse functional outcomes, expressed as the odds of not returning to pre-stroke functioning in their daily life (OR = 0.42; 95 CI 0.18 to 0.98. There was no significant effect on 30-day mortality. Compared with the UC arm, the hospital diagnostic and therapeutic procedures were performed more appropriately in the CP arm, and the evidence-based key interventions and organized care were more applied in the CP arm. Conclusions CPs can significantly improve the outcomes of patients with ischemic patients with stroke, indicating better application of evidence-based key interventions and of diagnostic and therapeutic procedures. This study tested a new

  3. Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25.

    Science.gov (United States)

    Li, Ying; Sheng, Kangliang; Chen, Jingyu; Wu, Yujing; Zhang, Feng; Chang, Yan; Wu, Huaxun; Fu, Jingjing; Zhang, Lingling; Wei, Wei

    2015-12-15

    This study was to investigate PGE2 and TNF-alpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells (DCs) and the effect of CP-25. Bone marrow DCs were isolated and stimulated by PGE2 and TNF-alpha respectively. The markers of maturation and activation expressed on DCs, such as CD40, CD80, CD83, CD86, MHC-II, and the ability of antigen uptake of DCs were analyzed by flow cytometry. The proliferation of T cells co-cultured with DCs, the signaling pathways of PGE2-EP4-cAMP and TNF-alpha-TRADD-TRAF2-NF-κB in DCs were analyzed. The results showed that both PGE2 and TNF-alpha up-regulated the expressions of CD40, CD80, CD83, CD86, and MHC-II, decreased the antigen uptake of DCs, and DCs stimulated by PGE2 or TNF-alpha could increase T cell proliferation. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased significantly the expressions of CD40, CD80, CD83, CD86 and MHC-II, increased the antigen uptake of DCs, and suppressed T cell proliferation induced by DCs. PGE2 increased the expressions of EP4, NF-κB and down-regulated cAMP level of DCs. TNF-alpha could also up-regulate TNFR1, TRADD, TRAF2, and NF-κB expression of DCs. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased the expressions of EP4 and NF-κB, increased cAMP level in DCs stimulated by PGE2. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) also could down-regulate significantly TNFR1, TRADD, TRAF2, and NF-κB expression in DCs stimulated by TNF-alpha. These results demonstrate that PGE2 and TNF-alpha could enhance DCs functions by mediating PGE2-EP4-cAMP pathway, TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathway respectively. CP-25 might inhibit the function of DCs through regulating PGE2-EP4-cAMP and TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Preferential effect of isoflurane on top-down vs. bottom-up pathways in sensory cortex.

    Science.gov (United States)

    Raz, Aeyal; Grady, Sean M; Krause, Bryan M; Uhlrich, Daniel J; Manning, Karen A; Banks, Matthew I

    2014-01-01

    The mechanism of loss of consciousness (LOC) under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up "core" thalamo-cortical (TC) vs. top-down cortico-cortical (CC) and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural basis of consciousness.

  5. Positive Effects of Negative Publicity: When Negative Reviews Increase Sales

    OpenAIRE

    Jonah Berger; Alan T. Sorensen; Scott J. Rasmussen

    2010-01-01

    Can negative information about a product increase sales, and if so, when? Although popular wisdom suggests that "any publicity is good publicity," prior research has demonstrated only downsides to negative press. Negative reviews or word of mouth, for example, have been found to hurt product evaluation and sales. Using a combination of econometric analysis and experimental methods, we unify these perspectives to delineate contexts under which negative publicity about a product will have posit...

  6. Full effects of land use change in the representative concentration pathways

    International Nuclear Information System (INIS)

    Davies-Barnard, T; Valdes, P J; Singarayer, J S; Pacifico, F M; Jones, C D

    2014-01-01

    Future land use change (LUC) is an important component of the IPCC representative concentration pathways (RCPs), but in these scenarios’ radiative forcing targets the climate impact of LUC only includes greenhouse gases. However, climate effects due to physical changes of the land surface can be as large. Here we show the critical importance of including non-carbon impacts of LUC when considering the RCPs. Using an ensemble of climate model simulations with and without LUC, we show that the net climate effect is very different from the carbon-only effect. Despite opposite signs of LUC, all the RCPs assessed here have a small net warming from LUC because of varying biogeophysical effects, and in RCP4.5 the warming is outside of the expected variability. The afforestation in RCP4.5 decreases surface albedo, making the net global temperature anomaly over land around five times larger than RCPs 2.6 and 8.5, for around twice the amount of LUC. Consequent changes to circulation in RCP4.5 in turn reduce Arctic sea ice cover. The small net positive temperature effect from LUC could make RCP4.5’s universal carbon tax, which incentivizes retaining and growing forest, counter productive with respect to climate. However, there are spatial differences in the balance of impacts, and potential climate gains would need to be assessed against other environmental aims. (letter)

  7. The Pathway to a Safe and Effective Spaceflight Medication Formulary: Expert Review Panel Recommendations

    Science.gov (United States)

    Daniels, V. R.; Bayuse, T. M.; Mulcahy, R. A.; McGuire, R. K. M.; Antonsen, E. L.

    2018-01-01

    Exploration spaceflight poses several challenges to the provision of a comprehensive medication formulary. This formulary must accommodate the size and space limitations of the spacecraft, while addressing individual medication needs and preferences of the crew, consequences of a degrading inventory over time, the inability to resupply used or expired medications, and the need to forecast the best possible medication candidates to treat conditions that may occur. The Exploration Medical Capability (ExMC) Element's Pharmacy Project Team has developed a research plan (RP) that is focused on evidence-based models and theories as well as new diagnostic tools, treatments, or preventive measures aimed to ensure an available, safe, and effective pharmacy sufficient to manage potential medical threats during exploration spaceflight. Here, we will discuss the ways in which the ExMC Pharmacy Project Team pursued expert evaluation and guidance, and incorporated acquired insight into an achievable research pathway, reflected in the revised RP.

  8. Modeling effective transmission pathways and control of the world's most successful parasite.

    Science.gov (United States)

    Turner, Matthew; Lenhart, Suzanne; Rosenthal, Benjamin; Zhao, Xiaopeng

    2013-06-01

    Toxoplasma gondii(T. gondii) is a single-celled, intracellular protozoan responsible for the disease toxoplasmosis. The parasite is prevalent worldwide, and it infects all warm-blooded vertebrates. Consumption of meats in which this parasite has encysted confers risk of infection to people and other animals, as does ingestion of water or foods contaminated with environmentally resistant oocysts excreted by cats. Vertical transmission (from mother to offspring) is also possible, leading to disease risk and contributing additional means of ensuring perpetuation of transmission. In this work, we adopt a differential equation model to investigate the effective transmission pathways of T. gondii, as well as potential control mechanisms. Detailed analyses are carried out to examine the significance of transmission routes, virulence, vertical transmission, parasite-induced changes in host behavior, and controls based on vaccination and harvesting. Modeling and analysis efforts may shed insights into understanding the complex life cycle of T. gondii. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Oxidative stress suppresses the cellular bioenergetic effect of the 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway

    Energy Technology Data Exchange (ETDEWEB)

    Módis, Katalin [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States); Asimakopoulou, Antonia [Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras (Greece); Coletta, Ciro [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States); Papapetropoulos, Andreas [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States); Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras (Greece); Szabo, Csaba, E-mail: szabocsaba@aol.com [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States)

    2013-04-19

    Highlights: •Oxidative stress impairs 3-MST-derived H{sub 2}S production in isolated enzyme and in isolated mitochondria. •This impairs the stimulatory bioenergetic effects of H{sub 2}S in hepatocytes. •This has implications for the pathophysiology of diseases with oxidative stress. -- Abstract: Recent data show that lower concentrations of hydrogen sulfide (H{sub 2}S), as well as endogenous, intramitochondrial production of H{sub 2}S by the 3-mercaptopyruvate (3-MP)/3-mercaptopyruvate sulfurtransferase (3-MST) pathway serves as an electron donor and inorganic source of energy to support mitochondrial electron transport and ATP generation in mammalian cells by donating electrons to Complex II. The aim of our study was to investigate the role of oxidative stress on the activity of the 3-MP/3-MST/H{sub 2}S pathway in vitro. Hydrogen peroxide (H{sub 2}O{sub 2}, 100–500 μM) caused a concentration-dependent decrease in the activity of recombinant mouse 3-MST enzyme. In mitochondria isolated from murine hepatoma cells, H{sub 2}O{sub 2} (50–500 μM) caused a concentration-dependent decrease in production of H{sub 2}S from 3-MP. In cultured murine hepatoma cells H{sub 2}O{sub 2}, (3–100 μM), did not result in overall cytotoxicity, but caused a partial decrease in basal oxygen consumption and respiratory reserve rapacity. The positive bioenergetic effect of 3-MP (100–300 nM) was completely abolished by pre-treatment of the cells with H{sub 2}O{sub 2} (50 μM). The current findings demonstrate that oxidative stress inhibits 3-MST activity and interferes with the positive bioenergetic role of the 3-MP/3-MST/H{sub 2}S pathway. These findings may have implications for the pathophysiology of various conditions associated with increased oxidative stress, such as various forms of critical illness, cardiovascular diseases, diabetes or physiological aging.

  10. The Pill Not Taken: Revisiting Physical Education Teacher Effectiveness in a Public Health Context

    Science.gov (United States)

    McKenzie, Thomas L.; Lounsbery, Monica A. F.

    2014-01-01

    In "Physical Education Teacher Effectiveness in a Public Health Context," we took a broad view of physical education (PE) teacher effectiveness that included public health need and support for PE. Public health officials have been consistent and fervent in their support of PE, and for more than two decades, they have called on schools to…

  11. The effect of bifenthrin on the dopaminergic pathway in juvenile rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Crago, Jordan; Schlenk, Daniel

    2015-05-01

    Bifenthrin is a type I pyrethroid pesticide, which has been shown to increase plasma estrogen concentrations in several fish models. The mechanism of action by which bifenthrin alters 17β-estradiol (E2) is unclear. E2 biosynthesis is regulated through pituitary follicle stimulating hormone, which is directly controlled by hypothalamic gonadotropin releasing hormone (GnRH2). Since dopaminergic signaling significantly influences GnRH2 release in fish, the goal of the study was to determine the effect of a 96 h and 2 weeks exposure to bifenthrin on dopaminergic signaling in juvenile rainbow trout (Oncorhynchus mykiss) (RT). Our results indicated that a decrease in dopamine receptor 2A (DR2A) expression was associated with a trend toward an increase in plasma E2 following exposure at 96 h and 2 weeks, and a significant increase in the relative expression of vitellogenin mRNA at 2 weeks. DR2A mRNA expression decreased 426-fold at 96 h and 269-fold at 2 weeks in the brains of 1.5 ppb (3.55 pM) bifenthrin treated RT. There was an increase in tyrosine hydroxylase transcript levels at 96 h, which is indicative of dopamine production in the brains of the 1.5 ppb (3.55 pM) bifenthrin treated RT. A significant increase in the relative expression of GnRH2 was observed at 96 h but a significant decrease was noted after 2 weeks exposure indicating potential feedback loop activation. These results indicate that the estrogenic-effects of bifenthrin may result in part from changes in signaling within the dopaminergic pathway, but that other feedback pathways may also be involved. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Molecular Pathways: Fumarate Hydratase-Deficient Kidney Cancer: Targeting the Warburg Effect in Cancer

    Science.gov (United States)

    Linehan, W. Marston; Rouault, Tracey A.

    2015-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a hereditary cancer syndrome in which affected individuals are at risk for development of cutaneous and uterine leiomyomas and an aggressive form of type II papillary kidney cancer. HLRCC is characterized by germline mutation of the tricarboxylic acid cycle (TCA) enzyme, fumarate hydratase (FH). FH-deficient kidney cancer is characterized by impaired oxidative phosphorylation and a metabolic shift to aerobic glycolysis, a form of metabolic reprogramming referred to as the Warburg effect. Increased glycolysis generates ATP needed for increased cell proliferation. In FH-deficient kidney cancer levels of AMPK, a cellular energy sensor, are decreased; resulting in diminished p53 levels, decreased expression of the iron importer, DMT1, leading to low cellular iron levels, and to enhanced fatty acid synthesis by diminishing phosphorylation of acetyl CoA carboxylase, a rate limiting step for fatty acid synthesis. Increased fumarate and decreased iron levels in FH-deficient kidney cancer cells inactivate prolyl hydroxylases, leading to stabilization of HIF1α, and increased expression of genes such as vascular endothelial growth factor (VEGF) and GLUT1 to provide fuel needed for rapid growth demands. Several therapeutic approaches for targeting the metabolic basis of FH-deficient kidney cancer are under development or are being evaluated in clinical trials, including the use of agents such as metformin, which would reverse the inactivation of AMPK, approaches to inhibit glucose transport, LDH-A, the anti-oxidant response pathway, the heme oxygenase pathway and approaches to target the tumor vasculature and glucose transport with agents such as bevacizumab and erlotinib. These same types of metabolic shifts, to aerobic glycolysis with decreased oxidative phosphorylation, have been found in a wide variety of other cancer types. Targeting the metabolic basis of a rare cancer such as fumarate hydratase

  13. Prediction of Effective Drug Combinations by Chemical Interaction, Protein Interaction and Target Enrichment of KEGG Pathways

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2013-01-01

    Full Text Available Drug combinatorial therapy could be more effective in treating some complex diseases than single agents due to better efficacy and reduced side effects. Although some drug combinations are being used, their underlying molecular mechanisms are still poorly understood. Therefore, it is of great interest to deduce a novel drug combination by their molecular mechanisms in a robust and rigorous way. This paper attempts to predict effective drug combinations by a combined consideration of: (1 chemical interaction between drugs, (2 protein interactions between drugs’ targets, and (3 target enrichment of KEGG pathways. A benchmark dataset was constructed, consisting of 121 confirmed effective combinations and 605 random combinations. Each drug combination was represented by 465 features derived from the aforementioned three properties. Some feature selection techniques, including Minimum Redundancy Maximum Relevance and Incremental Feature Selection, were adopted to extract the key features. Random forest model was built with its performance evaluated by 5-fold cross-validation. As a result, 55 key features providing the best prediction result were selected. These important features may help to gain insights into the mechanisms of drug combinations, and the proposed prediction model could become a useful tool for screening possible drug combinations.

  14. Innovative Pathways for Effective E-Governance in Africa: The Imperative of Authentic Leadership

    Directory of Open Access Journals (Sweden)

    Godwyns Agbude

    2015-12-01

    Full Text Available The evolving concept of e-governance has become one of the leading praxis of the 21st Century. This again reinforces, not just the importance of governance in human societies, but the need to redefine, reappraise, reinvent and redirect the path of governance towards effective and efficient service delivery. The paradigm of Science and Technology therefore presents the leading edge in our contemporary world thereby validating the viability of Information and Communication Technology (ICT in governance at diverse levels of operations. This paper, employs secondary data and presents the position that in the light of the fact that e-governance covers areas such as government, citizens and businesses/interest groups, the central place of leadership that will authenticate trust and confidence in the effective delivery of the e-governance protocols therefore becomes an imperative. In the gamut of literature on leadership, this paper identifies authentic leadership as a necessary condition that will facilitate effectiveness and efficiency of e-governance. This paper concludes that since there is a human dimension to the process of e-governance, creating innovative pathways for its effectiveness in Africa calls for authentic leadership which emphasizes constructive and developmental interactions between leaders and followers.

  15. Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution.

    Science.gov (United States)

    Shen, Yu-Sheng; Lung, Shih-Chun Candice

    2017-02-23

    Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, primary and secondary air pollutants separately using partial least squares model with data from Taiwan. The measurable characteristics of green structure include the largest patch percentage, landscape proportion, aggregation, patch distance, and fragmentation. The results showed that mortality of pneumonia and chronic lower respiratory diseases could be reduced by minimizing fragmentation and increasing the largest patch percentage of green structure, and the mediation effects are mostly through reducing air pollutants rather than temperature. Moreover, a high proportion of but fragmented green spaces would increase secondary air pollutants and enhance health risks; demonstrating the deficiency of traditional greening policy with primary focus on coverage ratio. This is the first research focusing on mediation effects of green structure characteristics on respiratory mortality, revealing that appropriate green structure planning can be a useful complementary strategy in environmental health management.

  16. Comparing New School Effects in Charter and Traditional Public Schools

    Science.gov (United States)

    Kelly, Andrew P.; Loveless, Tom

    2012-01-01

    This study investigates whether student achievement varies during the institutional life span of charter schools by comparing them to new public schools. The results show that there is little evidence that new public schools struggle with initial start-up issues to the same extent as new charter schools. Even after controlling for school…

  17. The effect of public health spending on under-five mortality rate in ...

    African Journals Online (AJOL)

    The effect of public health spending on under-five mortality rate in Uganda. ... PROMOTING ACCESS TO AFRICAN RESEARCH ... rate, Neonatal mortality rate, Public health expenditure, Sustainable Development Goals and Health status ...

  18. The effect of genistein on TGF-β signal, dysregulation of apoptosis, cyclooxygenase-2 pathway, and NF-kB pathway in mice peritoneum of endometriosis model

    Directory of Open Access Journals (Sweden)

    Sutrisno Sutrisno

    2017-12-01

    Full Text Available This research aimed to investigate the effect of genistein on TGF-β, dysregulation of apoptosis, NF-κB pathway, COX-2 pathway in mice of endometriosis model. Twenty-eight female mice (Mus musculus were divided into seven groups (n = 4, involving control (normal non-treated group; endometriosis group; the endometriosis group treated with various genistein dosages (0.78; 1.04; 1.3 mg/day for 15 days, and endometriosis group treated with standard drug, namely leuprolide acetate (0.00975 mg each day for 15 days or dienogest (0.0052 mg/day for 15 days. Mice of endometriosis model were made by implanting myometrial and endometrial tissues under the condition of immunodeficiency. The TGF-β, Bcl-2, Bax, NF-κB, COX-2, and PGE-2 were analyzed immunohistochemically. The increase of Bcl-2 expression in endometriosis was decreased significantly by genistein dosage of 0.78 and 1.3 mg/day (p < 0.05. The decrease of Bax expression in endometriosis was increased significantly by genistein dosage of 1.04 and 1.3 mg/day (p < 0.05. The implantation increased the expression of NF-κB, COX-2, and PGE significantly compared with the control group (p < 0.05. This increase was reduced significantly by the administration of genistein at dosage of 0.78 and 1.3 mg/day (p < 0.05. It can be concluded that genistein potentially inhibits endometriosis development through the normalization of apoptosis dysregulation, the inhibition of NF-κB and COX-2 pathways in the peritoneal tissues. Therefore, genistein can be used as a holistic treatment strategy for endometriosis.

  19. Flavonoid glycosides from Olax mannii: Structure elucidation and effect on the nuclear factor kappa B pathway.

    Science.gov (United States)

    Okoye, Festus B C; Sawadogo, Wamtinga Richard; Sendker, Jandirk; Aly, Amal H; Quandt, Bettina; Wray, Victor; Hensel, Andreas; Esimone, Charles O; Debbab, Abdessamad; Diederich, Marc; Proksch, Peter

    2015-12-24

    Olax mannii Oliv. (Olacaceae) is among the many medicinal plants used in Nigeria for the ethnomedicinal management of both cancer and inflammation. Such plants represent potential sources of innovative therapeutic agents for the treatment of cancer and other malignant disorders. While the majority of medicinal plants exert their anticancer effects by direct cytotoxicity on tumor cells, it is important that other mechanisms through which these plants can exhibit anticancer effects are investigated. Preliminary studies indicated that Olax mannii leaves are rich sources of novel flavonoid glycosides. The detailed chemistry as well the mechanisms through which these flavonoid constituents may exert their cancer chemo-preventive and therapeutic effects are, however, not yet investigated. The aim of this study is to carry out a detailed chemical investigation of Olax mannii leaves and the effects of the isolated constituents on the nuclear factor kappa B (NF-κB) pathway. A methanol leaf extract was subjected to various chromatographic separations to achieve isolation of flavonoid glycosides and the structures of the isolated compounds were elucidated by a combination of 1D and 2D NMR and high resolution mass spectrometry. Biological activities were assessed by measurement of cellular viability and proliferation using quantitative IncuCyte videomicroscopy, trypan blue staining and by quantification of the number of metabolically active K562 cells based on quantitation of ATP. The effect of the compounds on the inhibition of the NF-κB pathway as well as toxicity towards peripheral blood mononuclear cells to evaluate differential toxicity was also assayed. Chemical investigation of the methanol leaf extract of the plant material led to the isolation of three new flavonoid triglycosides, kaempferol 3-O-[α-D-apiofuranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O-α-L-rhamnopyranoside (1), kaempferol 3-O-[β-D-glucopyranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O

  20. Effective Two-way Communication of Environmental Hazards: Understanding Public Perception in the UK

    Science.gov (United States)

    Lorono-Leturiondo, Maria; O'Hare, Paul; Cook, Simon; Hoon, Stephen R.; Illingworth, Sam

    2017-04-01

    Climate change intensified hazards, such as floods and landslides, require exploring renewed ways of protecting at-risk communities (World Economic Forum 2016). Scientists are being encouraged to explore new pathways to work closely with affected communities in search of experiential knowledge that is able to complement and extend scientific knowledge (see for instance Whatmore and Landström 2011 and Höpner et al. 2010). Effective two-way communication of environmental hazards is, however, a challenge. Besides considering factors such as the purpose of communication, or the characteristics of the different formats; effective communication has to carefully acknowledge the personal framework of the individuals involved. Existing experiences, values, beliefs, and needs are critical determinants of the way they perceive and relate to these hazards, and in turn, of the communication process in which they are involved (Longnecker 2016 and Gibson et al. 2016). Our study builds on the need to analyze how the public perceives environmental hazards in order to establish forms of communication that work. Here we present early findings of a survey analysing the UK public's perception and outline how survey results can guide more effective two-way communication practices between scientists and affected communities. We explore the perception of environmental hazards in terms of how informed and concerned the public is, as well as how much ownership they claim over these phenomena. In order to gain a more accurate image, we study environmental hazards in relation to other risks threatening the UK, such as large-scale involuntary migration or unemployment (World Economic Forum 2016, Bord et al. 1998). We also explore information consumption in relation to environmental hazards and the public's involvement in advancing knowledge. All these questions are accompanied by an extensive demographics section that allows us to ascertain how the context or environment in which an

  1. Mechanism of Anti-glioblastoma Effect of Temzolomide Involved in ROS-Mediated SIRT 1 Pathway

    Directory of Open Access Journals (Sweden)

    Yuan Jiang

    2014-03-01

    Full Text Available Objective: To explore the new molecular mechanism of anti-tumor effect of temzolomide (TMZon glioblastoma cell strain. Methods: MTT methods and Hoechst 33342 staining method were applied to determine the effect of TMZ on the proliferation and apoptosis of glioblastoma cell strains U251 and SHG44, while flow cytometry was used to detect the impact of TMZ on cellular cycles. Additionally, DCFH-DA probe was adopted to test intracellular reactive oxygen species (ROS level while Real-time PCR and Western blot tests were applied to determine the influence of TMZ on SIRT1 expression. Results: TMZ in different concentrations added into glioblastoma cell strain for 72 h could concentration-dependently inhibit the proliferation of glioblastoma cells, 100 μmol/L of which could also block cells in phase G2/M and improve cellular apoptosis. In addition, TMZ could evidently increase intracellular ROS level so as to activate SIRT1. Conclusion: The mechanism of anti-tumor effect of TMZ on glioblastoma may be associated with ROS-induced SIRT1 pathway, providing theoretical basis for the clinical efficacy of TMZ.

  2. Effect of microenviroment hypoxia on glioma cells radiosensitivity through cancer stem cell pathway

    International Nuclear Information System (INIS)

    Tong Liumei; Feng Libo; Lu Xueguan; Chen Liesong; Guo Xinwei; Tian Ye

    2010-01-01

    Objective: To investigate the effect of microenviroment hypoxia on glioma cells radiosensitivity through cancer stem pathway, and to explore the related mechanism. Methods: Glioma cell lines SHG44 and U251 were cultured in normoxia (20% O 2 ) or continuous hypoxia (1% O 2 ) for 12 and 24 h. The fraction of glioma cells with positive expression of CD133 was assayed by flow cytometry. The radiosensitivity of glioma cells was determined by clonogenic cell assay. Western blotting was used to investigate the expressions of HIF-1 α and its downstream gene Notch 1. Results: The fraction of glioma cells with positive expression of CD133 was higher after hypoxic culture for 12 and 24 h than that of the corresponding cells cultured in normoxia. Compared to the cells cultured in normoxia, SF 2 (survival fraction at 2 Gy) were enhanced significantly in SHG44 and U251 cells cultured in hypoxia for 12 and 24 h. The OER (oxygen-enhancement ratio) of SHG44 cells in hypoxia for 12 and 24 h was 1.54 and 1.38, respectively. The OER of U251 cells was 1.44 and 1.23, respectively. The radiosensitivity of these two cell line was decreased in hypoxia. The protein expressions of HIF-1 α and Notch 1 genes were elevated more significantly for cells cultured in hypoxia for 12 and 24 h than for those in normoxia. Conclusions: Microenviroment hypoxia could increase the radioresistance of glioma cells through enrichment of cancer stem cells, and HIF-1 α-Notch 1 signal pathway may play an important role in this process. (authors)

  3. Effect of UV radiation and its implications on carotenoid pathway in Bixa orellana L.

    Science.gov (United States)

    Sankari, M; Hridya, H; Sneha, P; George Priya Doss, C; Ramamoorthy, Siva

    2017-11-01

    The current study was undertaken to analyse the effect of short-term UV-B and UV-C radiations in provoking carotenoid biosynthesis in Bixa orellana. Seeds of B. orellana were germinated and exposed to the short term UV pre-treatment under controlled environmental condition for 5days. The UV treated young seedlings response in pigment contents; antioxidant enzyme activity and mRNA gene expression level were analysed. The pigment content such as chlorophyll was increased in both UV-B and UV-C treated seedlings, but the total carotenoid level was decreased when compared to the control seedlings this can be attributed to the plant adaptability to survive in a stressed condition. The β-carotene level was increased in UV-B, and UV-C treated young seedlings. No significant changes have occurred in the secondary pigment such as bixin and ABA. The activity of the antioxidant enzymes such as catalase, peroxidase, and superoxide dismutase was significantly increased in UV-B treated seedlings when compared to the UV-C treated seedlings and control. The mRNA expression of the genes involved in bixin biosynthesis pathways such as DXS, PSY, PDS, LCY-β, LCY-ε, CMT, LCD, ADH and CCD genes showed different expression pattern in UV-B and UV-C treated young seedlings. Further we analysed the gene co-expression network to identify the genes which are mainly involved in carotenoid/bixin biosynthesis pathway. Form our findings the CCD, LCY, PDS, ZDS and PSY showed a close interaction. The result of our study shows that the short term UV-B and UV-C radiations induce pigment content, antioxidant enzyme activity and different gene expression pattern allowing the plant to survive in the oxidative stress condition. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Effects of glutamine, taurine and their association on inflammatory pathway markers in macrophages.

    Science.gov (United States)

    Sartori, Talita; Galvão Dos Santos, Guilherme; Nogueira-Pedro, Amanda; Makiyama, Edson; Rogero, Marcelo Macedo; Borelli, Primavera; Fock, Ricardo Ambrósio

    2018-06-01

    The immune system is essential for the control and elimination of infections, and macrophages are cells that act as important players in orchestrating the various parts of the inflammatory/immune response. Amino acids play important role in mediating functionality of the inflammatory response, especially mediating macrophages functions and cytokines production. We investigated the influence of glutamine, taurine and their association on the modulation of inflammatory pathway markers in macrophages. The RAW 264.7 macrophage cell line was cultivated in the presence of glutamine and taurine and proliferation rates, cell viability, cell cycle phases, IL-1α, IL-6, IL-10 and TNF-α as well as H 2 O 2 production and the expression of the transcription factor, NFκB, and its inhibitor, IκBα, were evaluated. Our results showed an increase in viable cells and increased proliferation rates of cells treated with glutamine concentrations over 2 mM, as well as cells treated with both glutamine and taurine. The cell cycle showed a higher percentage of cells in the phases S, G2 and M when they were treated with 2 or 10 mM glutamine, or with glutamine and taurine in cells stimulated with lipopolysaccharide. The pNFκB/NFκB showed reduced ratio expression when cells were treated with 10 mM of glutamine or with glutamine in association with taurine. These conditions also resulted in reduced TNF-α, IL-1α and H 2 O 2 production, and higher production of IL-10. These findings demonstrate that glutamine and taurine are able to modulate macrophages inflammatory pathways, and that taurine can potentiate the effects of glutamine, illustrating their immunomodulatory properties.

  5. Temporal expression profiling identifies pathways mediating effect of causal variant on phenotype.

    Directory of Open Access Journals (Sweden)

    Saumya Gupta

    2015-06-01

    Full Text Available Even with identification of multiple causal genetic variants for common human diseases, understanding the molecular processes mediating the causal variants' effect on the disease remains a challenge. This understanding is crucial for the development of therapeutic strategies to prevent and treat disease. While static profiling of gene expression is primarily used to get insights into the biological bases of diseases, it makes differentiating the causative from the correlative effects difficult, as the dynamics of the underlying biological processes are not monitored. Using yeast as a model, we studied genome-wide gene expression dynamics in the presence of a causal variant as the sole genetic determinant, and performed allele-specific functional validation to delineate the causal effects of the genetic variant on the phenotype. Here, we characterized the precise genetic effects of a functional MKT1 allelic variant in sporulation efficiency variation. A mathematical model describing meiotic landmark events and conditional activation of MKT1 expression during sporulation specified an early meiotic role of this variant. By analyzing the early meiotic genome-wide transcriptional response, we demonstrate an MKT1-dependent role of novel modulators, namely, RTG1/3, regulators of mitochondrial retrograde signaling, and DAL82, regulator of nitrogen starvation, in additively effecting sporulation efficiency. In the presence of functional MKT1 allele, better respiration during early sporulation was observed, which was dependent on the mitochondrial retrograde regulator, RTG3. Furthermore, our approach showed that MKT1 contributes to sporulation independent of Puf3, an RNA-binding protein that steady-state transcription profiling studies have suggested to mediate MKT1-pleiotropic effects during mitotic growth. These results uncover interesting regulatory links between meiosis and mitochondrial retrograde signaling. In this study, we highlight the advantage

  6. Effects of public premiums on children's health insurance coverage: evidence from 1999 to 2003.

    Science.gov (United States)

    Kenney, Genevieve; Hadley, Jack; Blavin, Fredric

    This study uses 2000 to 2004 Current Population Survey data to examine the effects of public premiums on the insurance coverage of children whose family incomes are between 100% and 300% of the federal poverty level. The analysis employs multinomial logistic models that control for factors other than premium costs. While the magnitude of the estimated effects varies across models, the results consistently indicate that raising public premiums reduces enrollment in public programs, with some children who forgo public coverage having private coverage instead and others being uninsured. The results indicate that public premiums have larger effects when applied to lower-income families.

  7. Mastering public health: essential skills for effective practice

    National Research Council Canada - National Science Library

    Levy, Barry S; Gaufin, Joyce R

    2012-01-01

    .... Designed for new and seasoned public health workers alike, this user-friendly guide focuses on the day-to-day practical skills and competencies that are often not taught in educational or training programs...

  8. PUBLIC-PRIVATE PARTNERSHIP AS EFFECTIVE MECHANISM OF SPORTS INFRASTRUCTURE

    Directory of Open Access Journals (Sweden)

    D. P. Moskvin

    2012-01-01

    Full Text Available The article discusses the current state of sports infrastructure in Russia and also explores the experience of using public-private partnership at Olympic facilities construction in Sochi.

  9. Effective Practices for Evaluating Education and Public Outreach Programs

    Science.gov (United States)

    Wilkerson, S.

    2013-12-01

    Stephanie Baird Wilkerson, PhD Carol Haden EdD Magnolia Consulting,LLC Education and public outreach (EPO) program developers and providers seeking insights regarding effective practices for evaluating EPO activities programs benefit from understanding why evaluation is critical to the success of EPO activities and programs, what data collection methods are appropriate, and how to effectively communicate and report findings. Based on our extensive experience evaluating EPO programs, we will share lessons learned and examples of how these practices play out in actual evaluation studies. EPO program developers, providers, and evaluators must consider several factors that influence which evaluation designs and data collection methods will be most appropriate, given the nature of EPO programs. Effective evaluation practices of EPO programs take into account a program's phase of development, duration, and budget as well as a program's intended outcomes. EPO programs that are just beginning development will have different evaluation needs and priorities than will well-established programs. Effective evaluation practices consider the 'life' of a program with an evaluation design that supports a program's growth through various phases including development, revision and refinement, and completion. It would be premature and inappropriate to expect the attainment of longer-term outcomes of activities during program development phases or early stages of implementation. During program development, EPO providers should clearly define program outcomes that are feasible and appropriate given a program's scope and expected reach. In many respects, this directly relates to the amount of time, or duration, intended audiences participate in EPO programs. As program duration increases so does the likelihood that the program can achieve longer-term outcomes. When choosing which outcomes are reasonable to impact and measure, program duration should be considered. Effective evaluation

  10. To the public procurement cost-effectiveness evaluation in Russia

    Directory of Open Access Journals (Sweden)

    Timur V. Kramin

    2017-12-01

    Full Text Available Objective to search for and substantiate the single criterion of economic efficiency of state purchases in Russia. Methods econometric modelling benchmarking. Results the article identifies the need to assess the effectiveness of the state purchases system in Russia under the conditions of its reforming. The studies are analyzed which are devoted to the approaches to estimating the state purchases efficiency and the problems of ensuring the transparency of purchasing procedures. Special attention is paid to the analysis of studying the benchmarking of state purchases which helped to identify the key areas of benchmarking focusing on certain performance indicators. To implement the research objective the purchases effectiveness was analyzed from the viewpoint of the savings achieved. For this we studied the evaluation of savings in purchases as reflected in various sources of information including the data of the state statistics authorities audit and monitoring of purchases. As a result of the data systematization and generalization we identified a functional relationship between savings in purchases and the average number of participants in the purchasing process. A similar conclusion was formulated according to the analysis of indicators of the national rating of purchases transparency. There was also built a functional dependency of the discount on increasing the number of purchasing participants up to five for different ways of determining the provider. A slowdown of the discount to the initial price was revealed as the number of eligible applications grows. Based on the regional rating of the public purchases ldquoPurchases 360rdquo a factor analysis of differences of the Russian constituent entities was carried out in terms of savings. The analysis confirmed the hypothesis about the existence of a relationship between savings and the level of competition in purchases. The study also identified other factors that determine the level of

  11. Centralized Management For Effective Public Diplomacy: Case of Hasabara

    Directory of Open Access Journals (Sweden)

    Vitaliy V. Kabernik

    2015-01-01

    Full Text Available The following paper is the first in the series dedicated to review and analysis of cases of centralization of public diplomacy affairs management for better promoting the agenda of the state. Introduction focuses on the erosion of traditional diplomatic practices shifting towards the stark attraction of soft power and public diplomacy. The evolution of modern public diplomacy in new media and the ways of its practical implementation reviewed, stating the raising power of non-government actors and mass media with their greater influence developing political agenda. The shift is analyzed on temporal basis bearing in mind inception of web 2.0 happening almost simultaneously with theoretical basis of soft power and the role of public diplomacy in propagating it. The case outlined in the first part reviews the evolution of Israeli's Hasbara - public diplomacy apparatus implemented in Jewish State. This evolution demonstrates the shift from decentralized management and coordination paradigm towards structured complex of measures led by government bodies. The sources and reasons for such a shift are being analyzed while national specifics for public diplomacy coordination is outlined. Results of the study underline the deficiencies of the chosen centralization paradigm via government bodies' control. The approach is being compared with the current practices implemented in Russia, outlining the best practices and mistakes to avoid that could be deducted from Israeli experience.

  12. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication.

    Science.gov (United States)

    Bercik, P; Park, A J; Sinclair, D; Khoshdel, A; Lu, J; Huang, X; Deng, Y; Blennerhassett, P A; Fahnestock, M; Moine, D; Berger, B; Huizinga, J D; Kunze, W; McLean, P G; Bergonzelli, G E; Collins, S M; Verdu, E F

    2011-12-01

    The probiotic Bifidobacterium longum NCC3001 normalizes anxiety-like behavior and hippocampal brain derived neurotrophic factor (BDNF) in mice with infectious colitis. Using a model of chemical colitis we test whether the anxiolytic effect of B. longum involves vagal integrity, and changes in neural cell function. Methods  Mice received dextran sodium sulfate (DSS, 3%) in drinking water during three 1-week cycles. Bifidobacterium longum or placebo were gavaged daily during the last cycle. Some mice underwent subdiaphragmatic vagotomy. Behavior was assessed by step-down test, inflammation by myeloperoxidase (MPO) activity and histology. BDNF mRNA was measured in neuroblastoma SH-SY5Y cells after incubation with sera from B. longum- or placebo-treated mice. The effect of B. longum on myenteric neuron excitability was measured using intracellular microelectrodes. Chronic colitis was associated with anxiety-like behavior, which was absent in previously vagotomized mice. B. longum normalized behavior but had no effect on MPO activity or histological scores. Its anxiolytic effect was absent in mice with established anxiety that were vagotomized before the third DSS cycle. B. longum metabolites did not affect BDNF mRNA expression in SH-SY5Y cells but decreased excitability of enteric neurons. In this colitis model, anxiety-like behavior is vagally mediated. The anxiolytic effect of B. longum requires vagal integrity but does not involve gut immuno-modulation or production of BDNF by neuronal cells. As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system. © 2011 Blackwell Publishing Ltd.

  13. The effect of selected metals on the central metabolic pathways in ...

    African Journals Online (AJOL)

    compounds, interfere with xenobiotic metabolic pathways, and may also affect glycolysis, the Krebs cycle, oxidative phosphorylation, protein amino acid metabolism as well as carbohydrate and lipid metabolism. Therefore, in this review, we discuss the two phases of the central metabolic pathways, as well as how metals ...

  14. Effects of Bisphenol A on glucose homeostasis and brain insulin signaling pathways in male mice.

    Science.gov (United States)

    Fang, Fangfang; Chen, Donglong; Yu, Pan; Qian, Wenyi; Zhou, Jing; Liu, Jingli; Gao, Rong; Wang, Jun; Xiao, Hang

    2015-02-01

    The potential effects of Bisphenol A (BPA) on peripheral insulin resistance have recently gained more attention, however, its functions on brain insulin resistance are still unknown. The aim of the present study was to investigate the effects of BPA on insulin signaling and glucose transport in mouse brain. The male mice were administrated of 100 μg/kg/day BPA or vehicle for 15 days then challenged with glucose and insulin tolerance tests. The insulin levels were detected with radioimmunoassay (RIA), and the insulin signaling pathways were investigated by Western blot. Our results revealed that BPA significantly increased peripheral plasma insulin levels, and decreased the insulin signals including phosphorylated insulin receptor (p-IR), phosphorylated insulin receptor substrate 1 (p-IRS1), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular regulated protein kinases (p-ERK1/2) in the brain, though insulin expression in both hippocampus and profrontal cortex was increased. In parallel, BPA exposure might contribute to glucose transport disturbance in the brain since the expression of glucose transporters were markedly decreased. In conclusion, BPA exposure perturbs the insulin signaling and glucose transport in the brain, therefore, it might be a risk factor for brain insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Effects of Water Molecule on CO Oxidation by OH: Reaction Pathways, Kinetic Barriers, and Rate Constants.

    Science.gov (United States)

    Zhang, Linyao; Yang, Li; Zhao, Yijun; Zhang, Jiaxu; Feng, Dongdong; Sun, Shaozeng

    2017-07-06

    The water dilute oxy-fuel combustion is a clean combustion technology for near-zero emission power; and the presence of water molecule could have both kinetic and dynamic effects on combustion reactions. The reaction OH + CO → CO 2 + H, one of the most important elementary reactions, has been investigated by extensive electronic structure calculations. And the effects of a single water molecule on CO oxidation have been studied by considering the preformed OH(H 2 O) complex reacts with CO. The results show little change in the reaction pathways, but the additional water molecule actually increases the vibrationally adiabatic energy barriers (V a G ). Further thermal rate constant calculations in the temperature range of 200 to 2000 K demonstrate that the total low-pressure limit rate constant for the water assisted OH(H 2 O) + CO → CO 2 + H 2 O + H reaction is 1-2 orders lower than that of the water unassisted one, which is consistent with the change of V a G . Therefore, the hydrated radical OH(H 2 O) would actually slow down the oxidation of CO. Meanwhile, comparisons show that the M06-2X/aug-cc-pVDZ method gives a much better estimation in energy and thus is recommended to be employed for direct dynamics simulations.

  16. The effect of the pathway to a two degrees warmer world on the regional temperature change of Europe

    Directory of Open Access Journals (Sweden)

    Cathrine Fox Maule

    2017-08-01

    Full Text Available The purpose of this study is to investigate if the pathway to reach a 2 degree warmer world influences the regional climate in Europe at the time of 2 degrees of global warming above the pre-industrial level. We have investigated this using climate change data from ensembles of both Global Climate Models and Regional Climate Models. We compare the change of regional temperature in Europe to the global temperature change for different emission scenarios, following the IPCC Representative Concentration Pathways (RCP, to see if the pathway has any influence. We find that there is a small but significant difference in the regional temperature change, but the effect is small compared to internal variability on the timescales involved in reaching +2 degrees for the investigated emission scenarios. From an adaptation point of view, reaching +2 degrees as slowly as possible will obviously allow for a longer time period to implement adaptation measures to mitigate the effect of climate change.

  17. Possible involvement of the JAK/STAT signaling pathway in N-acetylcysteine-mediated antidepressant-like effects.

    Science.gov (United States)

    Al-Samhari, Marwa M; Al-Rasheed, Nouf M; Al-Rejaie, Salim; Al-Rasheed, Nawal M; Hasan, Iman H; Mahmoud, Ayman M; Dzimiri, Nduna

    2016-03-01

    Advances in depression research have targeted inflammation and oxidative stress to develop novel types of treatment. The JAK/STAT signaling pathway plays pivotal roles in immune and inflammatory responses. The present study was designed to investigate the effects of N-acetylcysteine, a putative precursor of the antioxidant glutathione, in an animal model of depression, with an emphasis on the JAK/STAT signaling pathway. Fluoxetine, a classical antidepressant drug was also under investigation. Male Wistar rats were subjected to forced swimming test and given N-acetylcysteine and fluoxetine immediately after the pre-test session, 5 h later and 1 h before the test session of the forced swimming test. N-acetylcysteine decreased immobility time (P acetylcysteine produced significant (P acetylcysteine significantly (P acetylcysteine. Therefore, depression research may target the JAK/STAT signaling pathway to provide a novel effective therapy. © 2015 by the Society for Experimental Biology and Medicine.

  18. The Mediating Effect of Social Capital on the Relationship Between Public Health Managers' Transformational Leadership and Public Health Nurses' Organizational Empowerment in Korea Public Health.

    Science.gov (United States)

    Jun, Soo Young

    2017-12-01

    This study was to verify the effect of public health nurse's (PHN's) social capital on the relationship between public health manager's (PHM's) transformational leadership and PHN's organizational empowerment in Korea public health. This was a cross-sectional descriptive study involving 303 PHNs from public health centers in Daegu and Gyeongsangbuk-do cities in South Korea. Data were collected from February 29, 2016 to April 8, 2016, using structured questionnaires which included general characteristics, transformational leadership, organizational empowerment, and social capital. Data were analyzed using descriptive statistics, correlations, and structural equation model. PHM's transformational leadership has a positive effect on PHN's social capital and PHN's organizational empowerment. Social capital had a mediating effect between transformational leadership and organizational empowerment in PHNs. This study suggests that PHM's transformational leadership is a contributing factor to improve PHN's organizational empowerment, and transformational leadership can lead to improve PHN's organizational empowerment through PHN's social capital. So, an intervention program to promote organizational empowerment should include strategies to enhance PHM's transformational leadership as well as to improve PHN's social capital. Copyright © 2017. Published by Elsevier B.V.

  19. Identifying effective pathways in a successful continuous quality improvement programme: the GEDAPS study.

    Science.gov (United States)

    Bodicoat, Danielle H; Mundet, Xavier; Gray, Laura J; Cos, Xavier; Davies, Melanie J; Khunti, Kamlesh; Cano, Juan-Franciso

    2014-12-01

    Continuous quality improvement programmes often target several aspects of care, some of which may be more effective meaning that resources could be focussed on these. The objective was to identify the effective and ineffective aspects of a successful continuous quality improvement programme for individuals with type 2 diabetes in primary care. Data were from a series of cross-sectional studies (GEDAPS) in primary care, Catalonia, Spain, in 55 centres (2239 participants) in 1993, and 92 centres (5819 participants) in 2002. A structural equation modelling approach was used. The intervention was associated with improved microvascular outcomes through microalbuminuria and funduscopy screening, which had a direct effect on microvascular outcomes, and through attending 2-4 nurse visits and having ≥1 blood pressure measurement, which acted through reducing systolic blood pressure. The intervention was associated with improved macrovascular outcomes through blood pressure measurement and attending 2-4 nurse visits (through systolic blood pressure) and having ≥3 education topics, ≥1 HbA1c measurement and adequate medication (through HbA1c). Cholesterol measurement, weight measurement and foot examination did not contribute towards the effectiveness of the intervention. The pathways through which a continuous quality improvement programme appeared to act to reduce microvascular and macrovascular complications were driven by reductions in systolic blood pressure and HbA1c, which were attained through changes in nurse and education visits, measurement and medication. This suggests that these factors are potential areas on which future quality improvement programmes should focus. © 2014 John Wiley & Sons, Ltd.

  20. Co-LncRNA: investigating the lncRNA combinatorial effects in GO annotations and KEGG pathways based on human RNA-Seq data.

    Science.gov (United States)

    Zhao, Zheng; Bai, Jing; Wu, Aiwei; Wang, Yuan; Zhang, Jinwen; Wang, Zishan; Li, Yongsheng; Xu, Juan; Li, Xia

    2015-01-01

    Long non-coding RNAs (lncRNAs) are emerging as key regulators of diverse biological processes and diseases. However, the combinatorial effects of these molecules in a specific biological function are poorly understood. Identifying co-expressed protein-coding genes of lncRNAs would provide ample insight into lncRNA functions. To facilitate such an effort, we have developed Co-LncRNA, which is a web-based computational tool that allows users to identify GO annotations and KEGG pathways that may be affected by co-expressed protein-coding genes of a single or multiple lncRNAs. LncRNA co-expressed protein-coding genes were first identified in publicly available human RNA-Seq datasets, including 241 datasets across 6560 total individuals representing 28 tissue types/cell lines. Then, the lncRNA combinatorial effects in a given GO annotations or KEGG pathways are taken into account by the simultaneous analysis of multiple lncRNAs in user-selected individual or multiple datasets, which is realized by enrichment analysis. In addition, this software provides a graphical overview of pathways that are modulated by lncRNAs, as well as a specific tool to display the relevant networks between lncRNAs and their co-expressed protein-coding genes. Co-LncRNA also supports users in uploading their own lncRNA and protein-coding gene expression profiles to investigate the lncRNA combinatorial effects. It will be continuously updated with more human RNA-Seq datasets on an annual basis. Taken together, Co-LncRNA provides a web-based application for investigating lncRNA combinatorial effects, which could shed light on their biological roles and could be a valuable resource for this community. Database URL: http://www.bio-bigdata.com/Co-LncRNA/. © The Author(s) 2015. Published by Oxford University Press.

  1. Effects of aerosol emission pathways on future warming and human health

    Science.gov (United States)

    Partanen, Antti-Ilari; Matthews, Damon

    2016-04-01

    The peak global temperature is largely determined by cumulative emissions of long-lived greenhouse gases. However, anthropogenic emissions include also so-called short-lived climate forcers (SLCFs), which include aerosol particles and methane. Previous studies with simple models indicate that the timing of SLCF emission reductions has only a small effect on the rate of global warming and even less of an effect on global peak temperatures. However, these simple model analyses do not capture the spatial dynamics of aerosol-climate interactions, nor do they consider the additional effects of aerosol emissions on human health. There is therefore merit in assessing how the timing of aerosol emission reductions affects global temperature and premature mortality caused by elevated aerosol concentrations, using more comprehensive climate models. Here, we used an aerosol-climate model ECHAM-HAMMOZ to simulate the direct and indirect radiative forcing resulting from aerosol emissions. We simulated Representative Concentration Pathway (RCP) scenarios, and we also designed idealized low and high aerosol emission pathways based on RCP4.5 scenario (LOW and HIGH, respectively). From these simulations, we calculated the Effective Radiative Forcing (ERF) from aerosol emissions between 1850 and 2100, as well as aerosol concentrations used to estimate the premature mortality caused by particulate pollution. We then use the University of Victoria Earth System Climate Model to simulate the spatial and temporal pattern of climate response to these aerosol-forcing scenarios, in combination with prescribed emissions of both short and long-lived greenhouse gases according to the RCP4.5 scenario. In the RCP scenarios, global mean ERF declined during the 21st century from -1.3 W m-2 to -0.4 W m-2 (RCP8.5) and -0.2 W m-2 (RCP2.6). In the sensitivity scenarios, the forcing at the end of the 21st century was -1.6 W m-2 (HIGH) and practically zero (LOW). The difference in global mean temperature

  2. Inferring the functional effect of gene expression changes in signaling pathways

    Science.gov (United States)

    Sebastián-León, Patricia; Carbonell, José; Salavert, Francisco; Sanchez, Rubén; Medina, Ignacio; Dopazo, Joaquín

    2013-01-01

    Signaling pathways constitute a valuable source of information that allows interpreting the way in which alterations in gene activities affect to particular cell functionalities. There are web tools available that allow viewing and editing pathways, as well as representing experimental data on them. However, few methods aimed to identify the signaling circuits, within a pathway, associated to the biological problem studied exist and none of them provide a convenient graphical web interface. We present PATHiWAYS, a web-based signaling pathway visualization system that infers changes in signaling that affect cell functionality from the measurements of gene expression values in typical expression microarray case–control experiments. A simple probabilistic model of the pathway is used to estimate the probabilities for signal transmission from any receptor to any final effector molecule (taking into account the pathway topology) using for this the individual probabilities of gene product presence/absence inferred from gene expression values. Significant changes in these probabilities allow linking different cell functionalities triggered by the pathway to the biological problem studied. PATHiWAYS is available at: http://pathiways.babelomics.org/. PMID:23748960

  3. Estimated effects of adding universal public coverage of an essential medicines list to existing public drug plans in Canada.

    Science.gov (United States)

    Morgan, Steven G; Li, Winny; Yau, Brandon; Persaud, Nav

    2017-02-27

    Canada's universal health care system does not include universal coverage of prescription drugs. We sought to estimate the effects of adding universal public coverage of an essential medicines list to existing public drug plans in Canada. We used administrative and market research data to estimate the 2015 shares of the volume and cost of prescriptions filled in the community setting that were for 117 drugs on a model list of essential medicines for Canada. We compared prices of these essential medicines in Canada with prices in the United States, Sweden and New Zealand. We estimated the cost of adding universal public drug coverage of these essential medicines based on anticipated effects on medication use and pricing. The 117 essential medicines on the model list accounted for 44% of all prescriptions and 30% of total prescription drug expenditures in 2015. Average prices of generic essential medicines were 47% lower in the US, 60% lower in Sweden and 84% lower in New Zealand; brand-name drugs were priced 43% lower in the US. Estimated savings from universal public coverage of these essential medicines was $4.27 billion per year (range $2.72 billion to $5.83 billion; 28% reduction) for patients and private drug plan sponsors, at an incremental government cost of $1.23 billion per year (range $373 million to $1.98 billion; 11% reduction). Our analysis showed that adding universal public coverage of essential medicines to the existing public drug plans in Canada could address most of Canadians' pharmaceutical needs and save billions of dollars annually. Doing so may be a pragmatic step forward while more comprehensive pharmacare reforms are planned. © 2017 Canadian Medical Association or its licensors.

  4. Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets.

    Science.gov (United States)

    Bijak, Michal; Szelenberger, Rafal; Dziedzic, Angela; Saluk-Bijak, Joanna

    2018-02-10

    Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly reduces the risk of peripheral artery disease, myocardial infarction, ischemic stroke, and vascular death. Recent studies demonstrated the inhibition of ADP-induced blood platelet activation by three major compounds of the flavonolignans group: silybin, silychristin, and silydianin. For this reason, the aim of the current work was to verify the effects of silybin, silychristin, and silydianin on ADP-induced physiological platelets responses, as well as mechanisms of P2Y12-dependent intracellular signal transduction. We evaluated the effect of tested flavonolignans on ADP-induced blood platelets' aggregation in platelet-rich plasma (PRP) (using light transmission aggregometry), adhesion to fibrinogen (using the static method), and the secretion of PF-4 (using the ELISA method). Additionally, using the double labeled flow cytometry method, we estimated platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. We demonstrated a dose-dependent reduction of blood platelets' ability to perform ADP-induced aggregation, adhere to fibrinogen, and secrete PF-4 in samples treated with flavonolignans. Additionally, we observed that all of the tested flavonolignans were able to increase VASP phosphorylation in blood platelets samples, which is correlated with P2Y12 receptor inhibition. All of these analyses show that silychristin and silybin have the strongest inhibitory effect on blood platelet activation by ADP, while silydianin also inhibits the ADP pathway, but to a lesser extent. The results obtained in this study clearly demonstrate that silybin, silychristin, and silydianin have inhibitory properties against the P2Y12 receptor and block ADP-induced blood platelet

  5. Local and distal effects of arbuscular mycorrhizal colonization on direct pathway Pi uptake and root growth in Medicago truncatula

    Science.gov (United States)

    Watts-Williams, Stephanie J.; Jakobsen, Iver; Cavagnaro, Timothy R.; Grønlund, Mette

    2015-01-01

    Two pathways exist for plant Pi uptake from soil: via root epidermal cells (direct pathway) or via associations with arbuscular mycorrhizal (AM) fungi, and the two pathways interact in a complex manner. This study investigated distal and local effects of AM colonization on direct root Pi uptake and root growth, at different soil P levels. Medicago truncatula was grown at three soil P levels in split-pots with or without AM fungal inoculation and where one root half grew into soil labelled with 33P. Plant genotypes included the A17 wild type and the mtpt4 mutant. The mtpt4 mutant, colonized by AM fungi, but with no functional mycorrhizal pathway for Pi uptake, was included to better understand effects of AM colonization per se. Colonization by AM fungi decreased expression of direct Pi transporter genes locally, but not distally in the wild type. In mtpt4 mutant plants, direct Pi transporter genes and the Pi starvation-induced gene Mt4 were more highly expressed than in wild-type roots. In wild-type plants, less Pi was taken up via the direct pathway by non-colonized roots when the other root half was colonized by AM fungi, compared with non-mycorrhizal plants. Colonization by AM fungi strongly influenced root growth locally and distally, and direct root Pi uptake activity locally, but had only a weak influence on distal direct pathway activity. The responses to AM colonization in the mtpt4 mutant suggested that in the wild type, the increased P concentration of colonized roots was a major factor driving the effects of AM colonization on direct root Pi uptake. PMID:25944927

  6. Differential effects of 17 alpha-ethinylestradiol on the neutral and acidic pathways of bile salt synthesis in the rat

    NARCIS (Netherlands)

    Koopen, NR; Post, SM; Wolters, H; Havinga, R; Stellaard, F; Boverhof, R; Kuipers, F; Princen, HMG

    Effects of 17 alpha-ethinylestradiol (EE) on the neutral and acidic biosynthetic pathways of bile salt (BS) synthesis were evaluated in rats with an intact enterohepatic circulation and in rats with long-term bile diversion to induce BS synthesis, For this purpose, bile salt pool composition,

  7. The effect of alterations in total coenzyme A on metabolic pathways in the liver and heart

    International Nuclear Information System (INIS)

    Schlosser, C.A.S.

    1989-01-01

    The first set of experiments involved in vitro experiments using primary cultures of rat hepatocytes. A range of conditions were developed which resulted in cell cultures with variations in total CoA over a range of 1.3 to 2.9 nmol/mg protein with identical hormonal activation which simulated metabolic stress. Elevations of total CoA levels above that of controls due to preincubation with cyanamide plus pantothenate were correlated with diminished rates of total ketone body production, 3-hydroxybutyrate production and ratios of 3 hydroxybutyrate/acetoactetate with palmitate as substrate. In contrast, cells with elevated total CoA levels had higher rates of [ 14 C] CO 2 production from radioactive palmitate which implied greater flux of acetyl CoA units into the TCA cycle and less to the pathway of ketogenesis. The second set of experiments were designed to alter total CoA levels in vivo by maintaining rats on a chronic ethanol diet with or without pantothenate-supplementation. The effect of alterations of CoA on mitochondrial metabolism was evaluated by measuring substrate oxidation rates in liver and heat mitochondria as well as ketone body production with palmitoyl-1-carnitine as substrate

  8. Effect of uric acid on inflammatory COX-2 and ROS pathways in vascular smooth muscle cells.

    Science.gov (United States)

    Oğuz, Nurgül; Kırça, Mustafa; Çetin, Arzu; Yeşilkaya, Akın

    2017-10-01

    Hyperuricemia is thought to play a role in cardiovascular diseases (CVD), including hypertension, coronary artery disease and atherosclerosis. However, exactly how uric acid contributes to these pathologies is unknown. An underlying mechanism of inflammatory diseases, such as atherosclerosis, includes enhanced production of cyclooxygenase-2 (COX-2) and superoxide anion. Here, we aimed to examine the effect of uric acid on inflammatory COX-2 and superoxide anion production and to determine the role of losartan. Primarily cultured vascular smooth muscle cells (VSMCs) were time and dose-dependently induced by uric acid and COX-2 and superoxide anion levels were measured. COX-2 levels were determined by ELISA, and superoxide anion was measured by the superoxide dismutase (SOD)-inhibitable reduction of ferricytochrome c method. Uric acid elevated COX-2 levels in a time-dependent manner. Angiotensin-II receptor blocker, losartan, diminished uric-acid-induced COX-2 elevation. Uric acid also increased superoxide anion level in VSMCs. Uric acid plays an important role in CVD pathogenesis by inducing inflammatory COX-2 and ROS pathways. This is the first study demonstrating losartan's ability to reduce uric-acid-induced COX-2 elevation.

  9. Effect of various gases and chemical catalysts on phenol degradation pathways by pulsed electrical discharges

    Energy Technology Data Exchange (ETDEWEB)

    Shen Yongjun [Institute of Environmental Pollution Control Technologies, Zhejiang University, Hangzhou 310028 (China); Lei Lecheng [Institute of Environmental Pollution Control Technologies, Zhejiang University, Hangzhou 310028 (China)], E-mail: lclei@zju.edu.cn; Zhang Xingwang; Zhou Minghua; Zhang Yi [Institute of Environmental Pollution Control Technologies, Zhejiang University, Hangzhou 310028 (China)

    2008-02-11

    The processes of phenol degradation by pulsed electrical discharges were investigated under several kinds of discharge atmospheres (oxygen, argon, nitrogen and ozone) and chemical catalysts (ferrous ion and hydrogen peroxide). The temporal variations of the concentrations of phenol and the intermediate products were monitored by HPLC and GC-MS, respectively. It has been found that the effect of various gases bubbling on phenol degradation rate ranked in the following order: oxygen-containing ozone > oxygen > argon > nitrogen. The high gas bubbling flow rate was beneficial to the removal of phenol. It was found that the degradation proceeded differently when in the presence and absence of catalysts. The phenol removal rate was increased when ferrous ion was added. This considerable enhancement may be due to the Fenton's reaction. What's more, putting the chemical additives hydrogen peroxide into the reactor led to a dramatic increase in phenol degradation rate. The mechanism was due to the direct or indirect photolysis and pyrolysis destruction in plasma channel. Furthermore, the intermediate products were monitored by GC-MS under three degradation conditions. More THBs were generated under degradation conditions without gases bubbling or adding any catalyst, and more DHBs under the condition of adding ferrous ion, and more carboxylic acids under the condition of oxygen-containing ozone gas bubbling. Consequently, three distinct degradation pathways based on different conditions were proposed.

  10. Effect of various gases and chemical catalysts on phenol degradation pathways by pulsed electrical discharges.

    Science.gov (United States)

    Shen, Yongjun; Lei, Lecheng; Zhang, Xingwang; Zhou, Minghua; Zhang, Yi

    2008-02-11

    The processes of phenol degradation by pulsed electrical discharges were investigated under several kinds of discharge atmospheres (oxygen, argon, nitrogen and ozone) and chemical catalysts (ferrous ion and hydrogen peroxide). The temporal variations of the concentrations of phenol and the intermediate products were monitored by HPLC and GC-MS, respectively. It has been found that the effect of various gases bubbling on phenol degradation rate ranked in the following order: oxygen-containing ozone>oxygen>argon>nitrogen. The high gas bubbling flow rate was beneficial to the removal of phenol. It was found that the degradation proceeded differently when in the presence and absence of catalysts. The phenol removal rate was increased when ferrous ion was added. This considerable enhancement may be due to the Fenton's reaction. What's more, putting the chemical additives hydrogen peroxide into the reactor led to a dramatic increase in phenol degradation rate. The mechanism was due to the direct or indirect photolysis and pyrolysis destruction in plasma channel. Furthermore, the intermediate products were monitored by GC-MS under three degradation conditions. More THBs were generated under degradation conditions without gases bubbling or adding any catalyst, and more DHBs under the condition of adding ferrous ion, and more carboxylic acids under the condition of oxygen-containing ozone gas bubbling. Consequently, three distinct degradation pathways based on different conditions were proposed.

  11. Effect of various gases and chemical catalysts on phenol degradation pathways by pulsed electrical discharges

    International Nuclear Information System (INIS)

    Shen Yongjun; Lei Lecheng; Zhang Xingwang; Zhou Minghua; Zhang Yi

    2008-01-01

    The processes of phenol degradation by pulsed electrical discharges were investigated under several kinds of discharge atmospheres (oxygen, argon, nitrogen and ozone) and chemical catalysts (ferrous ion and hydrogen peroxide). The temporal variations of the concentrations of phenol and the intermediate products were monitored by HPLC and GC-MS, respectively. It has been found that the effect of various gases bubbling on phenol degradation rate ranked in the following order: oxygen-containing ozone > oxygen > argon > nitrogen. The high gas bubbling flow rate was beneficial to the removal of phenol. It was found that the degradation proceeded differently when in the presence and absence of catalysts. The phenol removal rate was increased when ferrous ion was added. This considerable enhancement may be due to the Fenton's reaction. What's more, putting the chemical additives hydrogen peroxide into the reactor led to a dramatic increase in phenol degradation rate. The mechanism was due to the direct or indirect photolysis and pyrolysis destruction in plasma channel. Furthermore, the intermediate products were monitored by GC-MS under three degradation conditions. More THBs were generated under degradation conditions without gases bubbling or adding any catalyst, and more DHBs under the condition of adding ferrous ion, and more carboxylic acids under the condition of oxygen-containing ozone gas bubbling. Consequently, three distinct degradation pathways based on different conditions were proposed

  12. The Effective Public Manager. Achieving Success in Government. First Edition.

    Science.gov (United States)

    Cohen, Steven

    The problems faced by public managers in managing an agency's internal operations and communicating with the outside world are described, and strategies for addressing these management problems are provided, as is personal advice on how to build and maintain a professional reputation and advance in the bureaucratic hierarchy. The following…

  13. The Effect of Outsourcing on the Performance of Public Schools

    Science.gov (United States)

    Rivera, Lonny J.

    2009-01-01

    Public education in the 21st century is faced with many difficult challenges. The first and probably most common issue is related to finance. As the economy continues to worsen, school districts are forced to find new revenue streams while at the same time reducing expenditures. In the current economic climate, it is becoming more difficult for…

  14. Public - private interdependence: An effective tool in water supply services

    Directory of Open Access Journals (Sweden)

    Ana Elena Iosif

    2014-11-01

    Full Text Available The paper aims to study the impact of certain determinants on the choice of local authorities to use public - private interdependence for the provision of water supply services, based on the Spanish and Romanian local experiences. Being aware of their impact, the authorities could place a particular focus on the determinants that lead to local development. Several studies reveal that public – private interdependence is a powerful tool for building local development (Melo & do Carmo, 2008; Dessi & Floris, 2009 and states are interested in finding out ways to obtain it. The complex methodology of the paper was designed in accordance with the particularities of each country studied. Gathering the data for Romania implied conducting several interviews, and for Spain survey, exploratory analysis and semi-structured interviews were applied. The determinants’ influence was tested through logit or linear probability model. The analysis validates that population, density of population, indirect taxes, affiliation of the city representative to a certain political party is influencing the option of local public authorities. The paper brings recommendations on promoting public - private interdependence in water supply services. The paper is mainly valuable for the parallel that is made between Spain and Romania in water supply services and it brings progress in comparative country cases.

  15. When is public enforcement of insider trading regulations effective?

    NARCIS (Netherlands)

    Wielhouwer, J.L.

    2013-01-01

    In this paper we investigate when public enforcement of insider trading regulations reduces the amount of insider trading. We model a game between a potentially self-interested regulator enforcing insider trading laws and a trader who may be trading on inside information. We show that equilibrium

  16. The Effect of Leadership in a Public Bad Experiment

    NARCIS (Netherlands)

    Moxnes, E.; van der Heijden, E.C.M.

    2000-01-01

    With regard to global or regional environmental problems, do countries that take unilateral actions inspire other countries to curtail emissions?In this paper this possibility is investigated by the use of a novel design of a laboratory public bad experiment with a leader.Twelve groups of five

  17. Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

    Science.gov (United States)

    Koch, Karoline; Havermann, Susannah; Büchter, Christian

    2014-01-01

    Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research. PMID:24895670

  18. Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

    Directory of Open Access Journals (Sweden)

    Karoline Koch

    2014-01-01

    Full Text Available Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research.

  19. Cytochrome and Alternative Pathway Respiration in Tobacco (Effects of Salicylic Acid).

    Science.gov (United States)

    Rhoads, D. M.; McIntosh, L.

    1993-11-01

    In suspension cultures of NT1 tobacco (Nicotiana tabacum L. cv Bright Yellow) cells the cytochrome pathway capacity increased between d 3 and d 4 following subculturing and reached the highest level observed on d 7. The capacity decreased significantly by d 10 and was at the same level on d 14. Both alternative pathway capacity and the amount of the 35-kD alternative oxidase protein increased significantly between d 5 and d 6, reached the highest point observed on d 7, remained constant until d 10, and decreased by d 14. The highest capacities of the alternative and cytochrome pathways and the highest amount of the 35-kD protein were attained on the day that cell cultures reached a stationary phase of growth. Addition of salicylic acid to cell cultures on d 4 caused a significant increase in alternative pathway capacity and a dramatic accumulation of the 35-kD protein by 12 h. The alternative pathway capacity and the protein level reached the highest level observed by 16 h after salicylic acid addition, and the cytochrome pathway capacity was at about the same level at each time point. The accumulation of the 35-kD alternative oxidase protein was significantly decreased by addition of actinomycin D 1 h before salicylic acid and was blocked by addition of cycloheximide. These results indicate that de novo transcription and translation were necessary for salicylic acid to cause the maximum accumulation of the 35-kD protein.

  20. Neighborhood effects on birthweight: an exploration of psychosocial and behavioral pathways in Baltimore, 1995--1996.

    Science.gov (United States)

    Schempf, Ashley; Strobino, Donna; O'Campo, Patricia

    2009-01-01

    Neighborhood characteristics have been proposed to influence birth outcomes through psychosocial and behavioral pathways, yet empirical evidence is lacking. Using data from an urban, low-income sample, this study examined the impact of the neighborhood environment on birthweight and evaluated mediation by psychosocial and behavioral factors. The sample included 726 women who delivered a live birth at Johns Hopkins Hospital in Baltimore, Maryland, USA between 1995 and 1996. Census-tract data were used to create a principal component index of neighborhood risk based on racial and economic stratification (% Black, % poverty), social disorder (violent crime rate), and physical deterioration (% boarded-up housing) (alpha=0.82). Information on sociodemographic, psychosocial, and behavioral factors was gathered from a postpartum interview and medical records. Random intercept multilevel models were used to estimate neighborhood effects and assess potential mediation. Controlling for sociodemographic characteristics, a standard deviation increase in neighborhood risk conferred a 76g birthweight decrement. This represents an approximate 300g difference between the best and worst neighborhoods. Although stress (daily hassles), perceived locus-of-control, and social support were related to birthweight, their adjustment reduced the neighborhood coefficient by only 12%. In contrast, the neighborhood effect was reduced by an additional 30% and was no longer statistically significant after adjustment for the behavioral factors of smoking, drug use, and delayed prenatal care. These findings suggest that neighborhood factors may influence birthweight by shaping maternal behavioral risks. Thus, neighborhood level interventions should be considered to address multiple maternal and infant health risks. Future studies should examine more direct measures of neighborhood stress, such as perceived neighborhood disorder, and evaluate alternative mechanisms by which neighborhood factors

  1. Evaluating the Effects of Co-Production Initiatives in Public Service Organizations

    DEFF Research Database (Denmark)

    Brix, Jacob; Krogstrup, Hanne Kathrine; Mortensen, Nanna Møller

    2017-01-01

    A change from New Public Management to New Public Governance (NPG) does not occur overnight. This forces public service organizations to develop new hybrid organizational forms as strategic response to the current situation. In NPG the basic assumption is that coproduction will result in increased...... efficiency and effectiveness for public service organizations as a new organizational recipe. However, a recent review determines that only few empirical studies document these claimed effects. To enable the creation of more empirical evidence that establish the effects of co-production, the purpose of our...

  2. Sensation seeking and alcohol use by college students: examining multiple pathways of effects.

    Science.gov (United States)

    Yanovitzky, Itzhak

    2006-01-01

    This study tests the proposition that peer influence mediates the effect of sensation seeking, a personality trait, on alcohol use among college students. Cross-sectional data to test this proposition were collected from a representative sample of college students at a large public northeastern university (N = 427). Results of hierarchical regression analyses showed that, as hypothesized, sensation seeking influenced personal alcohol use both directly and indirectly, through its impact on students' frequency of association with alcohol-using peers and the size of their drinking norm misperception. The findings suggest that interventions that seek to limit the frequency in which high sensation seekers associate with peers whose alcohol use is extreme or, alternatively, seek to facilitate social interactions of high sensation seekers with normative peers, may supplement efforts to influence sensation seekers' alcohol and other drug use through tailored mass media advertisements.

  3. Linking public relations processes and organizational effectiveness at a state health department.

    Science.gov (United States)

    Wise, Kurt

    2003-01-01

    This qualitative case study explored a state health department's relationships with strategic constituencies from a public relations perspective. The relationships were explored within the theoretical framework of the Excellence Theory, the dominant paradigm in public research. Findings indicate application of the Excellence Theory has the potential to increase organizational effectiveness at public health entities. With respect to the case investigated, findings indicate that the state health department could increase its organizational effectiveness through the adoption of recommendations based on the Excellence Theory.

  4. Audit the effectiveness of the electronic system of public (state) procurement

    OpenAIRE

    Pysmenna, М.

    2017-01-01

    The study deals with the methodology of the audit the effectiveness of e-environment for public procurement. The purpose of this paper is deepening theoretical and methodological framework for auditing electronic systems for public (government) procurement. Research methods included analysis of legislation in the area of procurement, monitoring of individual transactions of public (state) procurement, interview with the responsible persons of budgetary funds on the assessment of the effective...

  5. Differentiating pathway-specific from nonspecific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development

    Science.gov (United States)

    The U.S. Environmental Protection Agency’s ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with potential ...

  6. Effect of science communication with the public on inference of risk perception of science and technology

    International Nuclear Information System (INIS)

    Kosugi, Motoko

    2006-01-01

    Our previous study showed a big difference between expert's own risk perception and experts' inference of the public risk perception about technologies. So, this study tried to clarify the effect of the perceived distance in risk perception between the public and experts themselves on forwardness in science communication to the public. The questionnaire survey results reaffirmed that experts were inclined to feel larger difference in risk perception between the public and themselves on the subject of their own specialty than of non-specialty. The result also suggested the tendency that the bigger experts recognized difference in risk perception from the public, the less they actually had experiences of science communication including communication with the public. Moreover, the result showed that experiences of science communication had positive effects on belief of the public's scientific literacy. (author)

  7. The effectiveness of performance measuring in Slovenian public libraries

    Directory of Open Access Journals (Sweden)

    Silva Novljan

    1997-01-01

    Full Text Available The article describes methods of performance measuring in Slovenian public libraries, and calls attention to the problems attached to it. The argued presumption is that the performance measuring carried out on the state level, is not always a sufficient and adequate foundation for plarming of the developmenl and functioning of an individual library which has to cater for the needs and wishes of the population in a certain area.

  8. The effects of affiliations on the initial public offering pricing

    OpenAIRE

    Geranio, Manuela; Mazzoli, Camilla; Palmucci, Fabrizio

    2017-01-01

    This paper studies the impact of affiliations between lead managers, venture capitalists, and institutional investors on the Initial Public Offering (IPO) pricing. Using a sample of 1996 US IPOs issued between 1997 and 2010, we find that affiliations strongly and positively affect the offer price by improving the information production process. We also show that the underpricing is affected by affiliations because of conflicts of interest that exist between the players: when an institutional ...

  9. The Effect of Gender in the Publication Patterns in Mathematics.

    Directory of Open Access Journals (Sweden)

    Helena Mihaljević-Brandt

    Full Text Available Despite the increasing number of women graduating in mathematics, a systemic gender imbalance persists and is signified by a pronounced gender gap in the distribution of active researchers and professors. Especially at the level of university faculty, women mathematicians continue being drastically underrepresented, decades after the first affirmative action measures have been put into place. A solid publication record is of paramount importance for securing permanent positions. Thus, the question arises whether the publication patterns of men and women mathematicians differ in a significant way. Making use of the zbMATH database, one of the most comprehensive metadata sources on mathematical publications, we analyze the scholarly output of ∼150,000 mathematicians from the past four decades whose gender we algorithmically inferred. We focus on development over time, collaboration through coautorships, presumed journal quality and distribution of research topics-factors known to have a strong impact on job perspectives. We report significant differences between genders which may put women at a disadvantage when pursuing an academic career in mathematics.

  10. The Effect of Gender in the Publication Patterns in Mathematics.

    Science.gov (United States)

    Mihaljević-Brandt, Helena; Santamaría, Lucía; Tullney, Marco

    2016-01-01

    Despite the increasing number of women graduating in mathematics, a systemic gender imbalance persists and is signified by a pronounced gender gap in the distribution of active researchers and professors. Especially at the level of university faculty, women mathematicians continue being drastically underrepresented, decades after the first affirmative action measures have been put into place. A solid publication record is of paramount importance for securing permanent positions. Thus, the question arises whether the publication patterns of men and women mathematicians differ in a significant way. Making use of the zbMATH database, one of the most comprehensive metadata sources on mathematical publications, we analyze the scholarly output of ∼150,000 mathematicians from the past four decades whose gender we algorithmically inferred. We focus on development over time, collaboration through coautorships, presumed journal quality and distribution of research topics-factors known to have a strong impact on job perspectives. We report significant differences between genders which may put women at a disadvantage when pursuing an academic career in mathematics.

  11. Publication planning: an effective corporate strategy to influence health professionals.

    Science.gov (United States)

    2013-12-01

    Pharmaceutical companies integrate scientific publications into the communication strategies they employ to influence the practices of health professionals. In their"publication plan", pharmaceutical companies, or the communication agencies they hire, develop key messages to promote their drugs and then plan in advance how, when and where to disseminate them in medical journals or at conferences. Although their true intent is promotional, these messages must appear to be purely scientific, and are therefore disseminated as research articles, review articles, editorials, commentaries. Publication planning involves the use of "ghost" authors who work directly for pharmaceutical companies, but whose contribution is rarely acknowledged in the final published article. Key opinion leaders are recruited as the honorary authors of these articles, to which they have made little, if any, contribution. The criteria for authorship set by journals that publish primary research articles do not provide adequate protection against the practice of ghost and honorary authorship. Certain journals publishing primary research derive a large proportion of their revenue from selling reprints used by pharmaceutical companies to promote their drugs, especially by their sales representatives.

  12. The effect of terrorism on public confidence : an exploratory study.

    Energy Technology Data Exchange (ETDEWEB)

    Berry, M. S.; Baldwin, T. E.; Samsa, M. E.; Ramaprasad, A.; Decision and Information Sciences

    2008-10-31

    A primary goal of terrorism is to instill a sense of fear and vulnerability in a population and to erode confidence in government and law enforcement agencies to protect citizens against future attacks. In recognition of its importance, the Department of Homeland Security includes public confidence as one of the metrics it uses to assess the consequences of terrorist attacks. Hence, several factors--including a detailed understanding of the variations in public confidence among individuals, by type of terrorist event, and as a function of time--are critical to developing this metric. In this exploratory study, a questionnaire was designed, tested, and administered to small groups of individuals to measure public confidence in the ability of federal, state, and local governments and their public safety agencies to prevent acts of terrorism. Data were collected from the groups before and after they watched mock television news broadcasts portraying a smallpox attack, a series of suicide bomber attacks, a refinery bombing, and cyber intrusions on financial institutions that resulted in identity theft and financial losses. Our findings include the following: (a) the subjects can be classified into at least three distinct groups on the basis of their baseline outlook--optimistic, pessimistic, and unaffected; (b) the subjects make discriminations in their interpretations of an event on the basis of the nature of a terrorist attack, the time horizon, and its impact; (c) the recovery of confidence after a terrorist event has an incubation period and typically does not return to its initial level in the long-term; (d) the patterns of recovery of confidence differ between the optimists and the pessimists; and (e) individuals are able to associate a monetary value with a loss or gain in confidence, and the value associated with a loss is greater than the value associated with a gain. These findings illustrate the importance the public places in their confidence in government

  13. The operations and effectiveness of public and private provision of solid waste collection services in Kampala

    NARCIS (Netherlands)

    Katusiimeh, M.W.; Mol, A.P.J.; Burger, C.P.J.

    2012-01-01

    This paper compares the operations and discusses the effectiveness of public and private sector provision of solid waste collection in Kampala, Uganda. Household data suggest that the private sector is more effective than the public sector. Private sector companies provide services like container

  14. The Role of MAPK and Dopaminergic Synapse Signaling Pathways in Antidepressant Effect of Electroacupuncture Pretreatment in Chronic Restraint Stress Rats

    Directory of Open Access Journals (Sweden)

    Xinjing Yang

    2017-01-01

    Full Text Available Acupuncture has demonstrated the function in ameliorating depressive-like behaviors via modulating PKA/CREB signaling pathway. To further confirm the antidepressant mechanism of EA on the mitogen-activated protein kinase (MAPK and dopaminergic synapse signaling pathways, 4 target proteins were detected based on our previous iTRAQ analysis. Rats were randomly divided into control group, model group, and electroacupuncture (EA group. Except for the control group, all rats were subjected to 28 days of chronic restraint stress (CRS protocols to induce depression. In the EA group, EA pretreatment at Baihui (GV20 and Yintang (GV29 was performed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes prior to restraint. The antidepressant-like effect of EA was measured by body weight and open-field test. The protein levels of DAT, Th, Mapt, and Prkc in the hippocampus were examined by using Western blot. The results showed EA could ameliorate the depression-like behaviors and regulate the expression levels of Prkc and Mapt in CRS rats. The effect of EA on DAT and Th expression was minimal. These findings implied that EA pretreatment could alleviate depression through modulating MAPK signaling pathway. The role of EA on dopaminergic synapse signaling pathways needs to be further explored.

  15. Neuroprotective effect of rapamycin on spinal cord injury via activation of the Wnt/β-catenin signaling pathway

    Directory of Open Access Journals (Sweden)

    Kai Gao

    2015-01-01

    Full Text Available The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guidance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord injury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, ca-spase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental findings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury.

  16. Effects of Qingshen Granules on the Oxidative Stress-NF/kB Signal Pathway in Unilateral Ureteral Obstruction Rats.

    Science.gov (United States)

    Jin, Hua; Wang, Yiping; Wang, Dong; Zhang, Lei

    2018-01-01

    Background . The activation of NF-kappa B (NF/kB) signaling pathway plays an important role in the process of epithelial-mesenchymal transition (EMT) and renal interstitial fibrosis (RIF) in renal tubules. The process of oxidative stress reaction in kidney is via excessive reactive oxygen species (ROS) production to activate NF/kB signaling pathway. Qingshen Granule (QSG) is an effective Chinese formula utilized to treat chronic renal failure. Previous studies confirmed that QSG could inhibit RIF in unilateral ureteral obstruction (UUO) rats. In this study, we used UUO rats to investigate the effects of QSG on oxidative stress and the activation of NF/kB signaling. Seventy male Sprague-Dawley (SD) rats were randomly divided into a sham group, UUO model group, Qingshen Granules (QSG) high-dose, medium-dose, and low-dose groups, PDTC group, and candesartan group (10 rats in each group). Our study demonstrated that oxidative stress-NF/kB signal pathway contributed to the formation of UUO renal interstitial fibrosis. QSG may protect against RIF by inhibiting the oxidative stress-NF/kB signal pathway, reducing inflammation, and improving renal tubular EMT.

  17. Effects of bifenthrin exposure on the estrogenic and dopaminergic pathways in zebrafish embryos and juveniles.

    Science.gov (United States)

    Bertotto, Luísa Becker; Richards, Jaben; Gan, Jay; Volz, David Christopher; Schlenk, Daniel

    2018-01-01

    Bifenthrin is a pyrethroid insecticide used in urban and agricultural applications. Previous studies have shown that environmentally relevant (ng/L) concentrations of bifenthrin increased plasma concentrations of 17β-estradiol (E2) and altered the expression of dopaminergic pathway components. The dopaminergic neurons can indirectly regulate E2 biosynthesis, suggesting that bifenthrin may disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Because embryos do not have a complete HPG axis, the hypothesis that bifenthrin impairs dopamine regulation was tested in embryonic and 1-mo-old juvenile zebrafish (Danio rerio) with exposure to measured concentrations of 0.34 and 3.1 µg/L bifenthrin for 96 h. Quantitative reverse transcriptase polymerase chain reaction was used to investigate transcripts of tyrosine hydroxylase (TH), dopamine receptor 1 (DR1) and 2A (DR2A), dopamine active transporter (DAT), estrogen receptor α (ERα), ERβ1, ERβ2, luteinizing hormone β (LHβ), follicle-stimulating hormone β (FSHβ), vitellogenin (VTG), cytochrome P450 cyp19a1a, and cyp19a1b. Levels of E2 were measured by enzyme-linked immunosorbent assay (ELISA). Dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations were measured by liquid chromatrography-tandem mass spectrometry (LC-MS/MS). Significant decreases in TH and DR1 transcripts and HVA levels, as well as ratios of HVA/dopamine and HVA+DOPAC/dopamine, in zebrafish embryos were observed after bifenthrin treatment. In juveniles, a significant increase in the expression of ERβ1 and the DOPAC to dopamine ratio was noted. These results show a possible antiestrogenic effect of bifenthrin in embryos, and estrogenicity in juveniles, indicating life-stage-dependent toxicity in developing fish. Environ Toxicol Chem 2018;37:236-246. © 2017 SETAC. © 2017 SETAC.

  18. Aqueous photochemical degradation of hydroxylated PAHs: Kinetics, pathways, and multivariate effects of main water constituents

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Linke; Na, Guangshui [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Chen, Chang-Er [Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ (United Kingdom); Li, Jun [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); College of Marine Science, Shanghai Ocean University, Shanghai 201306 (China); Ju, Maowei; Wang, Ying; Li, Kai [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Zhang, Peng, E-mail: pzhang@nmemc.org.cn [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Yao, Ziwei [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China)

    2016-03-15

    PAHs. • Hydroxylated PAHs intrinsically photodegrade fast in sunlit surface waters. • Reaction types and transformation pathways of 9-Hydroxyfluorene were clarified. • Photolysis kinetics was affected by multivariate effects of main water constituents. • The photomodified toxicity of 9-Hydroxyfluorene was examined using Vibrio fischeri.

  19. Effects of seasonality, transport pathway, and spatial structure on greenhouse gas fluxes in a restored wetland.

    Science.gov (United States)

    McNicol, Gavin; Sturtevant, Cove S; Knox, Sara H; Dronova, Iryna; Baldocchi, Dennis D; Silver, Whendee L

    2017-07-01

    Wetlands can influence global climate via greenhouse gas (GHG) exchange of carbon dioxide (CO 2 ), methane (CH 4 ), and nitrous oxide (N 2 O). Few studies have quantified the full GHG budget of wetlands due to the high spatial and temporal variability of fluxes. We report annual open-water diffusion and ebullition fluxes of CO 2 , CH 4 , and N 2 O from a restored emergent marsh ecosystem. We combined these data with concurrent eddy-covariance measurements of whole-ecosystem CO 2 and CH 4 exchange to estimate GHG fluxes and associated radiative forcing effects for the whole wetland, and separately for open-water and vegetated cover types. Annual open-water CO 2 , CH 4 , and N 2 O emissions were 915 ± 95 g C-CO 2  m -2  yr -1 , 2.9 ± 0.5 g C-CH 4  m -2  yr -1 , and 62 ± 17 mg N-N 2 O m -2  yr -1 , respectively. Diffusion dominated open-water GHG transport, accounting for >99% of CO 2 and N 2 O emissions, and ~71% of CH 4 emissions. Seasonality was minor for CO 2 emissions, whereas CH 4 and N 2 O fluxes displayed strong and asynchronous seasonal dynamics. Notably, the overall radiative forcing of open-water fluxes (3.5 ± 0.3 kg CO 2 -eq m -2  yr -1 ) exceeded that of vegetated zones (1.4 ± 0.4 kg CO 2 -eq m -2  yr -1 ) due to high ecosystem respiration. After scaling results to the entire wetland using object-based cover classification of remote sensing imagery, net uptake of CO 2 (-1.4 ± 0.6 kt CO 2 -eq yr -1 ) did not offset CH 4 emission (3.7 ± 0.03 kt CO 2 -eq yr -1 ), producing an overall positive radiative forcing effect of 2.4 ± 0.3 kt CO 2 -eq yr -1 . These results demonstrate clear effects of seasonality, spatial structure, and transport pathway on the magnitude and composition of wetland GHG emissions, and the efficacy of multiscale flux measurement to overcome challenges of wetland heterogeneity. © 2017 John Wiley & Sons Ltd.

  20. RETRACTED: The Mediating Effect of Social Capital on the Relationship Between Public Health Managers' Transformational Leadership and Public Health Nurses' Organizational Empowerment in Korea Public Health

    Directory of Open Access Journals (Sweden)

    Soo Young Jun, MPH, RN

    2017-12-01

    Full Text Available This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal.The Editor-in-Chief and ANR editorial board have decided to retract this article because the scientific integrity of the content cannot be guaranteed. The article shows evidence of redundant publication and falsification of instruments.This article was a duplicate of a paper that had already been published in Journal of the Korean Data & Information Science Society Vol 29, No. 3, May 2017. doi 10.7465/jkdi.2017.28.3.585 The identical data collection period, study sample, variables, and instruments between these two papers show strong evidence of plagiarism. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited.This article is published based on a master’s thesis (Kim YE. The effects of the transformational leadership of managers perceived by public health nurses and their social capital on empowerment [master’s thesis]. Dague (Korea: Kyungpook National University; 2016. p. 1-57. and the author of this dissertation is deleted. Inappropriate use of master’s thesis without appropriate disclosure and/or citation was made.The instruments [Multifactor leadership questionnaire (Kim DW. The relationship between transformational leadership and quality of nurses' care Service with nurses' organization citizenship behavior as a moderator. Health Soc Welf Rev. 2011;31(2:206e36. Korean, social capital (Han JW, Woo HY, Ju ES, Lim SH, Han SS. Effects of nurses' social capital on turnover intention: focused on the mediating effects organizational commitment and organizational cynicism. J Korean Acad Nurs. 2013;43(4:517e25. https://doi.org/10.4040/jkan.2013.43.4.517. Korean, and Organizational empowerment (Oh EH, Chung BY. The effect of

  1. Effects of Job Accessibility Improved by Public Transport System: Natural Experimental Evidence from the Copenhagen Metro

    DEFF Research Database (Denmark)

    Pons Rotger, Gabriel Angel; Nielsen, Thomas Alexander Sick

    2015-01-01

    This study examines the effect of accessibility to urban jobs via a public transport system on individual earnings and commuting behaviour. The effect of improved public transport based accessibility on these outcomes is determined by exploiting the exogenous variation in access to a public rail ...... with a change in commuting patterns as the improved access to public transport facilitates a shift from employment within the township to better paid jobs in the city centre, as well as in other suburbs of the Copenhagen Metropolitan area...

  2. Effects of Persuasive Appeals in Public Service Advertising

    Science.gov (United States)

    Lynn, Jerry R.

    1974-01-01

    Concludes that of four message types perceived on the basis of persuasive appeal--emotional, logical, source-attribute, and fear--emotional appeal is the most effective and source-attribute the least effective method of advertising. (RB)

  3. The effectiveness of internet cognitive behaviour therapy (iCBT for social anxiety disorder across two routine practice pathways

    Directory of Open Access Journals (Sweden)

    Alishia D. Williams

    2014-10-01

    Full Text Available Social anxiety disorder (SAD is a common, chronic and disabling mental disorder. Cognitive Behaviour Therapy (CBT is a highly effective treatment of SAD and internet CBT (iCBT offers a cost-effective and convenient alternative to face to face approaches, with high fidelity and demonstrated efficacy. The aim of the current paper was to evaluate the effectiveness of an iCBT programme for SAD (The This Way Up Clinic Shyness Programme when delivered in routine practice through two different pathways. Patients in the prescription pathway (Study 1, N = 368, 50% female, mean age = 34 were ‘prescribed’ the Shyness Programme by a registered practitioner of the This Way Up Clinic who supervised their progress throughout the programme. Patients in the referral pathway (Study 2, N = 192, 50% female, mean age = 36 were referred to the This Way Up Clinic and supervised by a specialist CBT clinician at the clinic. Intention-to-treat marginal model analyses demonstrated significant reductions in primary outcomes of social anxiety symptoms (Mini-SPIN and psychological distress (K10, corresponding to large effect sizes (Cohen's d = .82–1.09, 95% CIs .59–1.31 and secondary outcomes of impairment (WHODAS-II and depressive symptoms (PHQ9, corresponding to small effect sizes (Cohen's d = .36–.46, 95% CIs .19–.68 for patients in both pathways. Results provide evidence of the effectiveness of iCBT for social anxiety disorder when delivered in routine practice.

  4. A pivotal role of the jasmonic acid signal pathway in mediating radiation-induced bystander effects in Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ting; Xu, Wei; Deng, Chenguang; Xu, Shaoxin; Li, Fanghua; Wu, Yuejin; Wu, Lijun [Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Key Laboratory of Environmental Toxicology and Pollution Control Technology of Anhui Province, Hefei 230031 (China); Bian, Po, E-mail: bianpo@ipp.ac.cn [Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031 (China); Key Laboratory of Environmental Toxicology and Pollution Control Technology of Anhui Province, Hefei 230031 (China)

    2016-09-15

    Highlights: • The JA signal pathway plays a pivotal role in mediating radiation-induced bystander effects in Arabidopsis thaliana. • The JA signal pathway is involved in both the generation of bystander signals in irradiated roots and radiation responses in bystander aerial plants. • Over-accumulation of endogenous JA enhances the radiosensitivity of plants in terms of RIBE. - Abstract: Although radiation-induced bystander effects (RIBE) in Arabidopsis thaliana have been well demonstrated in vivo, little is known about their underlying mechanisms, particularly with regard to the participating signaling molecules and signaling pathways. In higher plants, jasmonic acid (JA) and its bioactive derivatives are well accepted as systemic signal transducers that are produced in response to various environmental stresses. It is therefore speculated that the JA signal pathway might play a potential role in mediating radiation-induced bystander signaling of root-to-shoot. In the present study, pretreatment of seedlings with Salicylhydroxamic acid, an inhibitor of lipoxigenase (LOX) in JA biosynthesis, significantly suppressed RIBE-mediated expression of the AtRAD54 gene. After root irradiation, the aerial parts of A. thaliana mutants deficient in JA biosynthesis (aos) and signaling cascades (jar1-1) showed suppressed induction of the AtRAD54 and AtRAD51 genes and TSI and 180-bp repeats, which have been extensively used as endpoints of bystander genetic and epigenetic effects in plants. These results suggest an involvement of the JA signal pathway in the RIBE of plants. Using the root micro-grafting technique, the JA signal pathway was shown to participate in both the generation of bystander signals in irradiated root cells and radiation responses in the bystander aerial parts of plants. The over-accumulation of endogenous JA in mutant fatty acid oxygenation up-regulated 2 (fou2), in which mutation of the Two Pore Channel 1 (TPC1) gene up-regulates expression of the LOX

  5. An investigation into the effectiveness of public entities’ procurement practices

    Directory of Open Access Journals (Sweden)

    Moitswadi Mofokeng

    2014-11-01

    Full Text Available The delivery of services through the procurement of goods and services requires proper strategic leadership and management processes. Inappropriate planning, under-spending of budgets and ineffective procurement form part of the root causes of poor service delivery, as this restricts the movement of resources to the right places. This study identified the leading procurement practices as: procurement strategy and leadership, the procurement process, human resource management, procurement information systems, supplier management and procurement performance management. These practices were then tested in public entities, mainly in Gauteng Province, South Africa, to determine the extent to which they are applied. The study found that there is a major divide between the perception of the level of application of the leading practices and actual implementation. Processes, skills, performance management, information technology (IT systems and supplier management are applied inadequately or inappropriately. Most entities thus show a poor understanding of customer needs and there seems to be a general lack of customer focus. The study highlighted the best practice areas in which public entities are able to focus their efforts to better achieve excellent customer service and thus service delivery.

  6. Vocational Study and Public Service Motivation: Disentangling the Socializing Effects of Higher Education

    DEFF Research Database (Denmark)

    Kjeldsen, Anne Mette

    2012-01-01

    Most studies of Public Service Motivation investigate differences in motivation between public and private sector employees, but how these differences emerge and evolve in a pre-entry setting is still puzzling. Based on cross-sectional survey data with 3,521 Danish students enrolled in different...... vocational studies and at different stages (years) of their educational programs, this article investigates the socializing effects of higher education into different levels of public service motivation. The analysis demonstrates that students’ levels of public service motivation at different stages...... of their educational programs depends on the field of study: The level of public service motivation among students in vocational studies aimed at jobs with core public service delivery stays the same during education, whereas the level of public service motivation among students in other fields increases substantively...

  7. Effect of the Fukushima nuclear disaster on global public acceptance of nuclear energy

    International Nuclear Information System (INIS)

    Kim, Younghwan; Kim, Minki; Kim, Wonjoon

    2013-01-01

    The Fukushima nuclear disaster has significantly changed public attitudes toward nuclear energy. It is important to understand how this change has occurred in different countries before the global community revises existing nuclear policies. This study examines the effect of the Fukushima disaster on public acceptance of nuclear energy in 42 countries. We find that the operational experience of nuclear power generation which has significantly affected positive public opinion about nuclear energy became considerably negative after the disaster, suggesting fundamental changes in public acceptance regardless of the level of acceptance before the disaster. In addition, contrary to our expectation, the proportion of nuclear power generation is positively and significantly related to public acceptance of nuclear energy after the Fukushima accident and government pressure on media content led to a greater decrease in the level of public acceptance after the accident. Nuclear energy policymakers should consider the varied factors affecting public acceptance of nuclear energy in each country depending on its historical, environmental, and geographical circumstances before they revise nuclear policy in response to the Fukushima accident. - Highlights: • Fukushima accident has negatively changed public attitudes toward nuclear energy. • Effect of operational experience became considerably negative after the accident. • Effect of proportion of nuclear power generation is positive after the accident. • Effect of government pressure on media content became negative after the accident. • Country specific policy responses on nuclear public acceptance are required

  8. Evaluation of the effective equivalent dose in the general public due to the discharge of uranium in groundwater

    International Nuclear Information System (INIS)

    Gordon, A.M.P.L.; Jacomino, V.M.F.

    1989-12-01

    Some facilities available at IPEN-CNEN/SP may discharge uranium in their liquid effluents. The uranium contents of these effluents are analyzed by photometry or fluorimetry, and according to the results obtained a decision is made, by the Environmental Monitoring Division, upon their discharge to the environment. In 1988 a total activity of 3.66x10 9 Bq of uranium was discharge in a volume of approximately 30 m 3 . The effective equivalent dose in the general public was evaluated by making a conservative assumption that all the liquid effluents containing uranium are discharged directly to the soil reaching the groundwater. The dose calculation was carried out by using a generic model which described the transport of radionuclides in the groundwater. In order to be conservative it was also assumed that the critical pathway is the direct in gestion of water through hypothetical wells around the Institute. Conservative assumptions were also made in the characterization of the local aquifer parameters such as vertical and longitudinal dispersivity, effective porosity of the soil, hydraulic conductivity etc., in roder to overestimate the effective equivalent dose. The result obtained, of 5.3x10 -10 mSv/a is far below the dose limit for the public adopted by the Radiological Protection Board. The derived limit for the discharge was also evaluated, using the same model, giving a result of 3.6x10 13 Bq/a. (author) [pt

  9. Effect of QSKL on MAPK and RhoA Pathways in a Rat Model of Heart Failure

    Directory of Open Access Journals (Sweden)

    Kai Xia

    2017-01-01

    Full Text Available Qishenkeli (QSKL is one of the Chinese medicine formulae for treating heart failure and has been shown to have an antifibrotic effect. However, the mechanism of its therapeutic effects remains unclear. In this study, we aimed to explore whether QSKL could exert an antifibrotic effect by attenuating ras homolog family member A (RhoA and mitogen activated protein kinase (MAPK pathways. Rats were randomly divided into sham group, model group, QSKL group, and positive control group. Heart failure was induced by ligation of the left ventricle anterior descending artery. Cardiac functions were measured by echocardiography and collagen deposition was assessed by Masson staining. Expressions of the key molecules involved in the RhoA and MAPK pathways were also measured. Twenty-one days after surgery, cardiac functions were severely impaired and collagen deposition was remarkable, while QSKL treatment could improve heart functions and alleviate collagen deposition. Further results demonstrated that the effects may be mediated by suppressing expressions of extracellular signal-regulated kinase (ERK and c-Jun N-terminal kinase (JNK. Moreover, expressions of RhoA, Rho-associated protein kinase 1/2 (ROCK1/2, and phosphorylated myosin light chain (p-MLC were also downregulated by QSKL compared with the model group. The cardioprotective mechanism of QSKL on heart failure is probably mediated by regulating both the MAPK and RhoA signaling pathways.

  10. Biphasic effects of FGF2 on odontoblast differentiation involve changes in the BMP and Wnt signaling pathways.

    Science.gov (United States)

    Sagomonyants, Karen; Mina, Mina

    2014-08-01

    Odontoblast differentiation during physiological and reparative dentinogenesis is dependent upon multiple signaling molecules, including fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs) and Wingless/Integrated (Wnt) ligands. Recent studies in our laboratory showed that continuous exposure of primary dental pulp cultures to FGF2 exerted biphasic effects on the expression of markers of dentinogenesis. In the present study, we examined the possible involvement of the BMP and Wnt signaling pathways in mediating the effects of FGF2 on dental pulp cells. Our results showed that stimulatory effects of FGF2 on dentinogenesis during the proliferation phase of growth were associated with increased expression of the components of the BMP (Bmp2, Dlx5, Msx2, Osx) and Wnt (Wnt10a, Wisp2) pathways, and decreased expression of an inhibitor of the Wnt signaling, Nkd2. Further addition of FGF2 during the differentiation/mineralization phase of growth resulted in decreased expression of components of the BMP signaling (Bmp2, Runx2, Osx) and increased expression of inhibitors of the Wnt signaling (Nkd2, Dkk3). This suggests that both BMP and Wnt pathways may be involved in mediating the effects of FGF2 on dental pulp cells.

  11. Synergy effects between MINUSTAH and public security in Brazil

    Directory of Open Access Journals (Sweden)

    Christoph Harig

    2015-03-01

    Full Text Available This article assesses the complex relationship between UN Peace Operations and public security in Brazil. It shows that there are obvious similarities at an operational level between military actions in MINUSTAH and Rio´s Pacification, which arguably result in reciprocal learning processes among troops. With the establishment of dedicated training centres and a considerable amount of practical experience in missions that differ significantly from combat-orientated warfare, soldiers are becoming increasingly familiar with police tasks. Considering the extension of the legal framework for allowing domestic military actions, I argue that this “police-ization of the military” (Dunlap, 1999, p. 222 is probably more significant for internal “Guaranteeing Law and Order” (GLO missions than for further Brazilian participations in Peace Operations.

  12. Effectiveness of presidents as public communicators and presidential performance

    Directory of Open Access Journals (Sweden)

    Virginia García Beaudoux

    2013-08-01

    Full Text Available In this paper, in the first place, we present perspectivas elaborated by various authors highlighting the efectiveness of presidents as public communicators as a relevant variable related to the prediction of presidential performance. Second, indicators for the empirical meassurment of the variable are proposed. Third, we discuss the results obtained by means of an empirical exploration that involved the application of the above mentioned indicators to the discourses of four argentinean presidents: Raúl Alfonsín (1983-1989, Carlos Menem (1989-1995 y 1995-1999, Fernando de la Rúa (1999-2001 and Néstor Kirchner (2003-2007. In the last part, we discuss the utility of the variable for evaluating and predicting presidential performance.

  13. CHARACTERISTICS OF SIGNALING PATHWAYS MEDIATING A CYTOTOXIC EFFECT OF DENDRITIC CELLS UPON ACTIVATED Т LYMPHOCYTES AND NK CELLS

    Directory of Open Access Journals (Sweden)

    T. V. Tyrinova

    2012-01-01

    Full Text Available Abstract. Cytotoxic/pro-apoptogenic effects of IFNα-induced dendritic cells (IFN-DCs directed against Т-lymphocytes and NK cells were investigated in healthy donors. Using an allogenic MLC system, it was revealed that IFN-DCs induce apoptosis of both activated CD4+ and CD8+ T-lymphocytes, and NK cells. Apoptosis of CD4+ and CD8+ T-lymphocytes induced by their interaction with IFN-DCs was mediated by various signaling pathways. In particular, activated CD4+Т-lymphocytes were most sensitive to TRAIL- и Fas/ FasL-transduction pathways, whereas activated CD8+ T-lymphocytes were induced to apoptosis via TNFα-mediated pathway. PD-1/B7-H1-signaling pathway also played a distinct role in cytotoxic activity of IFNDCs towards both types of T lymphocytes and activated NK cells. The pro-apoptogenic/cytotoxic activity of IFN-DC against activated lymphocytes may be regarded as a mechanism of a feedback regulation aimed at restriction of immune response and maintenance of immune homeostasis. Moreover, upregulation of proapoptogenic molecules on DCs under pathological conditions may lead to suppression of antigen-specific response, thus contributing to the disease progression.

  14. Outcome of slow pathway modulation for atrioventricular nodal reentrant tachycardia with 50 versus 30 watts-more power, more effect?

    Science.gov (United States)

    Dechering, Dirk G; Schleberger, Ruben; Greiser, Eva; Dickow, Jannis; Koebe, Julia; Frommeyer, Gerrit; Willems, Stephan; Eckardt, Lars; Hoffmann, Boris A; Wasmer, Kristina

    2018-03-19

    Slow pathway modulation is the treatment of choice in patients with atrioventricular nodal reentrant tachycardia (AVNRT). No comparative data on ablation strategies exist. Therefore, we sought to compare two common ablation approaches. We analyzed prospective ablation databases of two high-volume tertiary centers (> 1000 ablations/year) using either 30 or 50 W for slow pathway modulation from 2012 to 2013. We analyzed procedural characteristics as well as short- and long-term outcomes. Mean follow-up was 36 ± 9 months. Six hundred thirty-four patients (50 W center: n = 342, 30 W center: n = 292) were ablated. Slow pathway modulation was successful in 99% in both groups (p = ns). Periprocedural AV block occurred in nine patients (2.6%) in the 50 W and five patients (1.7%) in the 30 W group (p = 0.59), respectively. We documented no permanent higher-degree AV block. The number of RF lesions and seconds of RF delivery was significantly less in the 50 W group (p = 0.04 for number of lesions; p modulation are highly effective and safe. Significantly, fewer RF duration was necessary to modulate the slow pathway with higher power output (50 W). Our subgroup analysis suggests that males and females might benefit most from different modulation approaches.

  15. Three Models of Anthrax Toxin Effects on the MAP-Kinase Pathway and Macrophage Survival

    Science.gov (United States)

    2008-03-01

    2005). Apic, Gordana, Tijana Ignjatovic, Scott Boyer , and Robert B. Russell. “Illuminating drug discovery with biological pathways,” FEBS Letters...Molecular Biology Reviews, 68(2): 320–344 (June 2004). Sauro, Herbert M. and Boris N. Kholodenko. “Quantitative analysis of signaling networks

  16. Cutting-edge technology for public health workforce training in comparative effectiveness research.

    Science.gov (United States)

    Salinas-Miranda, Abraham A; Nash, Michelle C; Salemi, Jason L; Mbah, Alfred K; Salihu, Hamisu M

    2013-06-01

    A critical mass of public health practitioners with expertise in analytic techniques and best practices in comparative effectiveness research is needed to fuel informed decisions and improve the quality of health care. The purpose of this case study is to describe the development and formative evaluation of a technology-enhanced comparative effectiveness research learning curriculum and to assess its potential utility to improve core comparative effectiveness research competencies among the public health workforce. Selected public health experts formed a multidisciplinary research collaborative and participated in the development and evaluation of a blended 15-week comprehensive e-comparative effectiveness research training program, which incorporated an array of health informatics technologies. Results indicate that research-based organizations can use a systematic, flexible, and rapid means of instructing their workforce using technology-enhanced authoring tools, learning management systems, survey research software, online communities of practice, and mobile communication for effective and creative comparative effectiveness research training of the public health workforce.

  17. The Recruitment Process as a Part of Effective Human Resource Management in Public Administration in Croatia

    OpenAIRE

    Tišma, Sanja; Ozimec, Kristina

    2007-01-01

    Facing global trends, recognizing and retaining talented and perspective employees became an important issue in every public administration reform. Human resources management in public administration has a mission to help an institution to meet strategic goals by attracting, maintaining and managing employees more effectively. On its way to EU Croatia also has to cope with improvements and development of its public administration system with accent on HRM importance. Taking into account other...

  18. Modeling the effects of a Staphylococcal Enterotoxin B (SEB on the apoptosis pathway

    Directory of Open Access Journals (Sweden)

    Hammamieh Rasha

    2006-05-01

    Full Text Available Abstract Background The lack of detailed understanding of the mechanism of action of many biowarfare agents poses an immediate challenge to biodefense efforts. Many potential bioweapons have been shown to affect the cellular pathways controlling apoptosis 1234. For example, pathogen-produced exotoxins such as Staphylococcal Enterotoxin B (SEB and Anthrax Lethal Factor (LF have been shown to disrupt the Fas-mediated apoptotic pathway 24. To evaluate how these agents affect these pathways it is first necessary to understand the dynamics of a normally functioning apoptosis network. This can then serve as a baseline against which a pathogen perturbed system can be compared. Such comparisons can expose both the proteins most susceptible to alteration by the agent as well as the most critical reaction rates to better instill control on a biological network. Results We explore this through the modeling and simulation of the Fas-mediated apoptotic pathway under normal and SEB influenced conditions. We stimulated human Jurkat cells with an anti-Fas antibody in the presence and absence of SEB and determined the relative levels of seven proteins involved in the core pathway at five time points following exposure. These levels were used to impute relative rate constants and build a quantitative model consisting of a series of ordinary differential equations (ODEs that simulate the network under both normal and pathogen-influenced conditions. Experimental results show that cells exposed to SEB exhibit an increase in the rate of executioner caspase expression (and subsequently apoptosis of 1 hour 43 minutes (± 14 minutes, as compared to cells undergoing normal cell death. Conclusion Our model accurately reflects these results and reveals intervention points that can be altered to restore SEB-influenced system dynamics back to levels within the range of normal conditions.

  19. The Effect of Public Support on College Attainment

    Science.gov (United States)

    Trostel, Philip A.

    2012-01-01

    This study estimates the extent that state financial support for higher education raises college attainment. Despite its manifest importance for policy, this is the first study to estimate this effect directly. Many studies have estimated the effect of college price on attendance, but state support for higher education and college price do not…

  20. An evaluation framework for effective public participation in EIA in Pakistan

    International Nuclear Information System (INIS)

    Nadeem, Obaidullah; Fischer, Thomas B.

    2011-01-01

    Evaluating the effectiveness of public participation in EIA related decisions is of crucial importance for developing a better understanding of overall EIA effectiveness. This paper aims to contribute to the professional debate by establishing a country specific evaluation framework for Pakistan, which, it is suggested, could also potentially be used in other developing countries. The framework is used to evaluate performance of public participation in EIA in terms of 40 attributes for four selected projects from the province of Punjab. The evaluation is based on interviews with stakeholders, review of EIA reports as well as public hearing proceedings and environmental approval conditions. The evaluation of the selected projects revealed an overall weak influence of public participation on substantive quality of EIA and on the final decision. Overall, EIA public participation has succeeded in providing a more egalitarian environment. Furthermore, it appears fair to say that sufficient time for submitting written comments on EIA reports as well as for raising concerns during public hearings had been given. Also, public consultation was significantly contributing to educating participants. Despite some impediments, it is argued that public participation in EIA is gradually gaining ground in Pakistan. Recommendations to enhance EIA public participation effectiveness in Pakistan include applying a more proactive approach which should take place before EIA is conducted and before site selection for development projects is happening.

  1. Effect of terbinafine on the biosynthetic pathway of isoprenoid compounds in carrot suspension cultured cells.

    Science.gov (United States)

    Miras-Moreno, Begoña; Almagro, Lorena; Pedreño, María Angeles; Sabater-Jara, Ana Belén

    2018-04-21

    Terbinafine induced a significant increase of squalene production. Terbinafine increased the expression levels of squalene synthase. Cyclodextrins did not work as elicitors due to the gene expression levels obtained. Plant sterols are essential components of membrane lipids, which contributing to their fluidity and permeability. Besides their cholesterol-lowering properties, they also have anti-inflammatory, antidiabetic and anticancer activities. Squalene, which is phytosterol precursor, is widely used in medicine, foods and cosmetics due to its anti-tumor, antioxidant and anti-aging activities. Nowadays, vegetable oils constitute the main sources of phytosterols and squalene, but their isolation and purification involve complex extraction protocols and high costs. In this work, Daucus carota cell cultures were used to evaluate the effect of cyclodextrins and terbinafine on the production and accumulation of squalene and phytosterols as well as the expression levels of squalene synthase and cycloartenol synthase genes. D. carota cell cultures were able to produce high levels of extracellular being phytosterols in the presence of cyclodextrins (12 mg/L), these compounds able to increase both the secretion and accumulation of phytosterols in the culture medium. Moreover, terbinafine induced a significant increase in intracellular squalene production, as seen after 168 h of treatment (497.0 ± 23.5 µg g dry weight -1 ) while its extracellular production only increased in the presence of cyclodextrins.The analysis of sqs and cas gene expression revealed that cyclodextrins did not induce genes encoding enzymes involved in the phytosterol biosynthetic pathway since the expression levels of sqs and cas genes in cyclodextrin-treated cells were lower than in control cells. The results, therefore, suggest that cyclodextrins were only able to release phytosterols from the cells to the extracellular medium, thus contributing to their acumulation. To sum up, D. carota

  2. Effects of Job Accessibility Improved by Public Transport System: Natural Experimental Evidence from the Copenhagen Metro

    DEFF Research Database (Denmark)

    Pons Rotger, Gabriel Angel; Nielsen, Thomas Alexander Sick

    2015-01-01

    This study examines the effect of accessibility to urban jobs via a public transport system on individual earnings and commuting behaviour. The effect of improved public transport based accessibility on these outcomes is determined by exploiting the exogenous variation in access to a public rail...... and Metro system resulting from the construction of a new terminal Metro station connecting southern townships to Copenhagen city centre. The results show that public transport based job accessibility has a positive and permanent effect on individual earnings. The increase in earnings is associated...... with a change in commuting patterns as the improved access to public transport facilitates a shift from employment within the township to better paid jobs in the city centre, as well as in other suburbs of the Copenhagen Metropolitan area...

  3. Investigating the effectiveness of response strategies for vulnerabilities to corruption in the chinese public construction sector.

    Science.gov (United States)

    Shan, Ming; Chan, Albert P C; Le, Yun; Hu, Yi

    2015-06-01

    Response strategy is a key for preventing widespread corruption vulnerabilities in the public construction sector. Although several studies have been devoted to this area, the effectiveness of response strategies has seldom been evaluated in China. This study aims to fill this gap by investigating the effectiveness of response strategies for corruption vulnerabilities through a survey in the Chinese public construction sector. Survey data obtained from selected experts involved in the Chinese public construction sector were analyzed by factor analysis and partial least squares-structural equation modeling. Analysis results showed that four response strategies of leadership, rules and regulations, training, and sanctions, only achieved an acceptable level in preventing corruption vulnerabilities in the Chinese public construction sector. This study contributes to knowledge by improving the understanding of the effectiveness of response strategies for corruption vulnerabilities in the public construction sector of developing countries.

  4. Identifying new susceptibility genes on dopaminergic and serotonergic pathways for the framing effect in decision-making.

    Science.gov (United States)

    Gao, Xiaoxue; Liu, Jinting; Gong, Pingyuan; Wang, Junhui; Fang, Wan; Yan, Hongming; Zhu, Lusha; Zhou, Xiaolin

    2017-09-01

    The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing. Using genome-wide association data and the gene-based principal components regression method, we examined genetic variations of 26 genes on the pathways in 1317 Chinese Han participants. Consistent with previous studies, we found that the genetic variations of the SLC6A4 gene and the COMT gene were associated with the framing effect. More importantly, we demonstrated that the genetic variations of the aromatic-L-amino-acid decarboxylase (DDC) gene, which is involved in the synthesis of both dopamine and serotonin, contributed to individual differences in the susceptibility to framing. Our findings shed light on the understanding of the genetic basis of affective decision-making. © The Author (2017). Published by Oxford University Press.

  5. Identifying new susceptibility genes on dopaminergic and serotonergic pathways for the framing effect in decision-making

    Science.gov (United States)

    Gao, Xiaoxue; Liu, Jinting; Gong, Pingyuan; Wang, Junhui; Fang, Wan; Yan, Hongming; Zhu, Lusha

    2017-01-01

    Abstract The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing. Using genome-wide association data and the gene-based principal components regression method, we examined genetic variations of 26 genes on the pathways in 1317 Chinese Han participants. Consistent with previous studies, we found that the genetic variations of the SLC6A4 gene and the COMT gene were associated with the framing effect. More importantly, we demonstrated that the genetic variations of the aromatic-L-amino-acid decarboxylase (DDC) gene, which is involved in the synthesis of both dopamine and serotonin, contributed to individual differences in the susceptibility to framing. Our findings shed light on the understanding of the genetic basis of affective decision-making. PMID:28431168

  6. The effect of maternal diabetes on the Wnt-PCP pathway during embryogenesis as reflected in the developing mouse eye

    Directory of Open Access Journals (Sweden)

    Beatriz López-Escobar

    2015-02-01

    Full Text Available Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1 and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1gt/gt and Daam1gt/+ embryos develop ocular defects (anophthalmia or microphthalmia that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1gt/+ mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos.

  7. Synergistic effects of concurrent blockade of PI3K and MEK pathways in pancreatic cancer preclinical models.

    Directory of Open Access Journals (Sweden)

    Hua Zhong

    Full Text Available Patients with pancreatic cancer have dismal prognoses, and novel therapies are urgently needed. Mutations of the KRAS oncogene occur frequently in pancreatic cancer and represent an attractive target. Direct targeting of the predominant KRAS pathways have been challenging and research into therapeutic strategies have been now refocused on pathways downstream of KRAS, phosphoinositide 3-kinase (PI3K and mitogen-activated protein kinase (MAPK [MEK]. We hypothesized that concurrent inhibition of the PI3K and MEK pathways would result in synergistic antitumor activity, as it would circumvent the compensatory feedback loop between the two pathways. We investigated the combined effect of the PI3K inhibitor, GDC0941, and the MEK inhibitor, AZD6244, on cell viability, apoptosis and cell signaling in a panel of pancreatic cancer cell lines. An in vivo analysis was conducted on pancreatic cancer xenografts. While BxPC-3 (KRAS wild type and MIA PaCa-2 (KRAS mutated cell lines were sensitive to GDC0941 and AZD6244 as single agents, synergistic inhibition of tumor cell growth and induction of apoptosis were observed in both cell lines when the two drugs were combined. Interestingly, phosphorylation of the cap-dependent translational components, 4E-binding protein (p-4E-BP1 and S6 was found to be closely associated with sensitivity to GDC0941 and AZD6244. In BxPC-3 cell xenografts, survival differences were observed between the control and the AZD6244, GDC0941, and combination groups. Our study provides the rationale for concurrent targeting of the PI3K and MEK pathways, regardless of KRAS status, and suggests that phosphorylation of 4E-BP1and S6 can serve as a predictive biomarker for response to treatment.

  8. A Comparative Study of the Effect of Subliminal Messages on Public Speaking Ability.

    Science.gov (United States)

    Schnell, James A.

    A study investigated the effectiveness of subliminal techniques (such as tape recorded programs) for improving public speaking ability. It was hypothesized that students who used subliminal tapes to improve public speaking ability would perform no differently from classmates who listened to identical-sounding placebo tape programs containing no…

  9. Rolling back the public sector: differential effects on growth, employment and investment

    NARCIS (Netherlands)

    van der Ploeg, F.

    2006-01-01

    The macroeconomic effects of different ways of rolling back the welfare state are analysed. Cutting public spending on market goods induces a lower interest rate, a higher wage, a lower capital stock, and a fall in employment. Cutting public employment or the labour income tax rate leads, in

  10. Performance management and cost effectiveness of public services : empirical evidence from Dutch municipalities

    NARCIS (Netherlands)

    de Groot, Hans; van Hulst, B.L.

    2011-01-01

    The performance of public organizations is one of the key topics in public administration research. Cost-effectiveness as a dimension of performance has hardly been studied in this literature, however. Many governments currently are cutting budgets on an unprecedented scale after the world-wide

  11. Organizational crisis-denial strategy: the effect of denial on public framing

    NARCIS (Netherlands)

    van der Meer, T.G.L.A.

    2014-01-01

    By applying a framing perspective, this study explores the effect of a crisis-denial strategy on public response. The online public framing of a specific crisis is compared with the crisis-denial frame provided by the organization. An automated semantic-network analysis is used to identify frames

  12. Risk-based estimate of effect of foodborne diseases on public health, Greece

    NARCIS (Netherlands)

    Gkogka, E.; Reij, M.W.; Havelaar, A.H.; Zwietering, M.H.; Gorris, L.G.M.

    2011-01-01

    The public health effects of illness caused by foodborne pathogens in Greece during 1996–2006 was quantified by using publicly available surveillance data, hospital statistics, and literature. Results were expressed as the incidence of different disease outcomes and as disability-adjusted life years

  13. Afferent Pathway-Mediated Effect of α1 Adrenergic Antagonist, Tamsulosin, on the Neurogenic Bladder After Spinal Cord Injury.

    Science.gov (United States)

    Han, Jin-Hee; Kim, Sung-Eun; Ko, Il-Gyu; Kim, Jayoung; Kim, Khae Hawn

    2017-09-01

    The functions of the lower urinary tract (LUT), such as voiding and storing urine, are dependent on complex central neural networks located in the brain, spinal cord, and peripheral ganglia. Thus, the functions of the LUT are susceptible to various neurologic disorders including spinal cord injury (SCI). SCI at the cervical or thoracic levels disrupts voluntary control of voiding and the normal reflex pathways coordinating bladder and sphincter functions. In this context, it is noteworthy that α1-adrenoceptor blockers have been reported to relieve voiding symptoms and storage symptoms in elderly men with benign prostatic hyperplasia (BPH). Tamsulosin, an α1-adrenoceptor blocker, is also considered the most effective regimen for patients with LUT symptoms such as BPH and overactive bladder (OAB). In the present study, the effects of tamsulosin on the expression of c-Fos, nerve growth factor (NGF), and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the afferent micturition areas, including the pontine micturition center (PMC), the ventrolateral periaqueductal gray matter (vlPAG), and the spinal cord (L5), of rats with an SCI were investigated. SCI was found to remarkably upregulate the expression of c-Fos, NGF, and NADPH-d in the afferent pathway of micturition, the dorsal horn of L5, the vlPAG, and the PMC, resulting in the symptoms of OAB. In contrast, tamsulosin treatment significantly suppressed these neural activities and the production of nitric oxide in the afferent pathways of micturition, and consequently, attenuated the symptoms of OAB. Based on these results, tamsulosin, an α1-adrenoceptor antagonist, could be used to attenuate bladder dysfunction following SCI. However, further studies are needed to elucidate the exact mechanism and effects of tamsulosin on the afferent pathways of micturition.

  14. Global effects of the CSR-1 RNA interference pathway on the transcriptional landscape.

    Science.gov (United States)

    Cecere, Germano; Hoersch, Sebastian; O'Keeffe, Sean; Sachidanandam, Ravi; Grishok, Alla

    2014-04-01

    Argonaute proteins and their small RNA cofactors short interfering RNAs are known to inhibit gene expression at the transcriptional and post-transcriptional levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of endogenous siRNAs (endo-siRNAs) that are antisense to germline transcripts. However, its role in gene expression regulation remains controversial. Here we used genome-wide profiling of nascent RNA transcripts and found that the CSR-1 RNA interference pathway promoted sense-oriented RNA polymerase II transcription. Moreover, a loss of CSR-1 function resulted in global increase in antisense transcription and ectopic transcription of silent chromatin domains, which led to reduced chromatin incorporation of centromere-specific histone H3. On the basis of these findings, we propose that the CSR-1 pathway helps maintain the directionality of active transcription, thereby propagating the distinction between transcriptionally active and silent genomic regions.

  15. The Effect of Publicized Quality Information on Home Health Agency Choice.

    Science.gov (United States)

    Jung, Jeah Kyoungrae; Wu, Bingxiao; Kim, Hyunjee; Polsky, Daniel

    2016-12-01

    We examine consumers' use of publicized quality information in Medicare home health care markets, where consumer cost sharing and travel costs are absent. We report two findings. First, agencies with high quality scores are more likely to be preferred by consumers after the introduction of a public reporting program than before. Second, consumers' use of publicized quality information differs by patient group. Community-based patients have slightly larger responses to public reporting than hospital-discharged patients. Patients with functional limitations at the start of their care, at least among hospital-discharged patients, have a larger response to the reported functional outcome measure than those without functional limitations. In all cases of significant marginal effects, magnitudes are small. We conclude that the current public reporting approach is unlikely to have critical impacts on home health agency choice. Identifying and releasing quality information that is meaningful to consumers may help increase consumers' use of public reports. © The Author(s) 2015.

  16. Involvement of NO/cGMP pathway in the antidepressant-like effect of gabapentin in mouse forced swimming test.

    Science.gov (United States)

    Ostadhadi, Sattar; Kordjazy, Nastaran; Haj-Mirzaian, Arya; Ameli, Sanaz; Akhlaghipour, Golnoosh; Dehpour, AhmadReza

    2016-04-01

    Based on clinical studies regarding the beneficial effect of gabapentin in depression, we aimed to evaluate the antidepressant-like properties of gabapentin in mice and also the participation of nitric oxide (NO)/cyclic guanosine monophosphate pathway in this effect. The following drugs were used in this study: gabapentin; N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific NO synthase (NOS) inhibitor; 7-nitroindazole, a specific neuronal NOS inhibitor; aminoguanidine, a specific inducible NOS inhibitor; L-arginine, a NO precursor; and sildenafil, a phosphodiestrase inhibitor. Finally, we studied the behavioral effects through the forced swimming test (FST) and the changes of the hippocampus NO level through nitrite assay. The immobility time was significantly reduced after gabapentin administration. Co-administration of non-effective doses of gabapentin and L-NAME or 7-nitroindazole (7-NI) resulted in antidepressant-like effect in FST, while aminoguanidine did not affect the immobility time of gabapentin-treated mice. Furthermore, the antidepressant-like property of gabapentin was prevented by L-arginine or sildenafil. Also, the hippocampal nitrite level was significantly lower in gabapentin-treated mice relative to saline-injected mice, and co-administration of 7-NI with sub-effective gabapentin caused a significant decrease in hippocampal nitrite levels. Our results indicate that the antidepressant-like effect of gabapentin in the mice FST model is mediated at least in part through nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.

  17. Changing public attitudes towards corporal punishment: the effects of statutory reform in Sweden.

    Science.gov (United States)

    Roberts, J V

    2000-08-01

    One justification for a statutory ban on physical punishment is that passage of such legislation changes public attitudes towards the use of this form of parental discipline. The experience in Sweden is often cited as an example of legislation which changed public opinion. The aim of this brief article is to review the public opinion findings in Sweden in order to evaluate in greater detail the impact of changing the law. A search was conducted to generate all published and publicly-available quantitative surveys of the public in Sweden and elsewhere. The results of time-series analysis of the data are clear. The 1979 legal reform in Sweden did not reduce the level of public support for parental use of corporal punishment as a means of disciplining children. Support for physical punishment began declining years before the reform was passed and the decline was in no way accelerated by the law reform. Changes in public opinion may have generated the legal reform, but the reverse is not true. Data from other jurisdictions also support the view that there is no relationship between the status of the law and the nature of public views with regard to corporal punishment. This result is consistent with analyses of the effects of legal reforms in other areas. The Swedish ban on corporal punishment did not affect public attitudes. Changing public views requires other initiatives.

  18. Effect of ammonium and acetate on methanogenic pathway and methanogenic community composition

    DEFF Research Database (Denmark)

    Fotidis, Ioannis; Karakashev, Dimitar Borisov; Kotsopoulos, T. A.

    2013-01-01

    exposure to different ammonia concentrations. The methanogenic pathway was determined by following the production of (14) CH(4) and (14) CO(2) from acetate labeled in the methyl group (C-2). Microbial communities' composition was determined by fluorescence in situ hybridization. Upon acclimatization......Methanogenesis from acetate (aceticlastic methanogenesis or syntrophic acetate oxidation (SAO) coupled with hydrogenotrophic methanogenesis) is the most important step for the biogas process. The major environmental factors influencing methanogenesis are volatile fatty acids, ammonia, p...

  19. Neighborhood Effects on Birthweight: An Exploration of Psychosocial and Behavioral Pathways in Baltimore, 1995–1996

    OpenAIRE

    Schempf, Ashley; Strobino, Donna; O’Campo, Patricia

    2008-01-01

    Neighborhood characteristics have been proposed to influence birth outcomes through psychosocial and behavioral pathways, yet empirical evidence is lacking. Using data from an urban, low-income sample, this study examined the impact of the neighborhood environment on birthweight and evaluated mediation by psychosocial and behavioral factors. The sample included 726 women who delivered a live birth at Johns Hopkins Hospital in Baltimore, Maryland USA between 1995 and 1996. Census tract data we...

  20. [Effects of electromagnetic radiation on RAF/MEK/ERK signaling pathway in rats hippocampus].

    Science.gov (United States)

    Zuo, Hong-yan; Wang, De-wen; Peng, Rui-yun; Wang, Shui-ming; Gao, Ya-bing; Xu, Xin-ping; Ma, Jun-Jie

    2009-05-01

    To study the development of changes for signaling molecules related to Raf/MEK/ERK pathway in hippocampus of rats after electromagnetic radiation, and investigate the mechanisms of radiation injury. Rats were exposed to X-HPM, S-HPM and EMP radiation source respectively, and animal model of electromagnetic radiation was established. Western blot was used to detect the expression of Raf-1, phosphorylated Raf-1 and phospholylated ERK. The expression of Raf-1 down-regulated during 6 h-14 d after radiation, most significantly at 7 d, and recovered at 28 d. There was no significant difference between the radiation groups. The expression of phosphorylated Raf-1 and phosphorylated ERK both up-regulated at 6 h and 7 d after radiation, more significantly at 6 h, and the two microwave groups were more serious for phosphorylated ERK. During 6 h-14 d after S-HPM radiation, the expression of phosphorylated Raf-1 increased continuously, but phosphorylated ERK changed wavily, 6 h and 7 d were expression peak. Raf/MEK/ERK signaling pathway participates in the hippocampus injury induced by electromagnetic radiation. The excessive activation of ERK pathway may result in the apoptosis and death of neurons, which is the important mechanism of recognition disfunction caused by electromagnetic radiation.

  1. Public lighting.

    NARCIS (Netherlands)

    Schreuder, D.A.

    1986-01-01

    The function of public lighting and the relationship between public lighting and accidents are considered briefly as aspects of effective countermeasures. Research needs and recent developments in installation and operational described. Public lighting is an efficient accident countermeasure, but

  2. Intranet Effectiveness: A Public Relations Paper-and-Pencil Checklist.

    Science.gov (United States)

    Murgolo-Poore, Marie E.; Pitt, Leyland F.; Ewing, Michael T.

    2002-01-01

    Describes a process directed at developing a simple paper-and-pencil checklist to assess Intranet effectiveness. Discusses the checklist purification procedure, and attempts to establish reliability and validity for the list. Concludes by identifying managerial applications of the checklist, recognizing the limitations of the approach, and…

  3. Physical Education Teacher Effectiveness in a Public Health Context

    Science.gov (United States)

    McKenzie, Thomas L.; Lounsbery, Monica A. F.

    2013-01-01

    The health benefits of physical activity are well documented, and the important role that schools and physical education (PE) can play in reducing sedentary behavior and contributing to population health has been identified. Although effective teaching is ultimately judged by student achievement, a major component of teacher and school…

  4. Effective Schools. What Makes a Public School Work Well?

    Science.gov (United States)

    Our Children, 1998

    1998-01-01

    Most effective schools share a number of key characteristics, including clear-cut goals and objectives, adequate funding and financial management, quality academic programs, valid assessment programs, parent and family involvement, teacher and staff development, high expectations for students, community involvement, comprehensive support services,…

  5. Sources and pathways of selected organochlorine pesticides to the Arctic and the effect of pathway divergence on HCH trends in biota: a review

    International Nuclear Information System (INIS)

    Li, Y.F.; Macdonald, R.W.

    2005-01-01

    Historical global usage and emissions for organochlorine pesticides (OCPs), including hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethane (DDT), toxaphene and endosulfan, are presented. Relationships between the air concentrations of these OCPs and their global emissions are also discussed. Differences between the pathways of α- and β-HCH to the Arctic Ocean are described in the context of environmental concentrating and diluting processes. These concentrating and diluting processes are shown to control the temporal and spatial loading of northern oceans and that the HCH burdens in marine biota from these oceans respond accordingly. The HCHs provide an elegant example of how hemispheric-scale solvent switching processes can alter the ocean into which an HCH congener partitions, how air-water partitioning controls the pathway for HCHs entering the Arctic, and how the various pathways impact spatial and temporal trends of HCH residues in arctic animals feeding out of marine and terrestrial foodwebs

  6. Oxidation of benzoic acid by heat-activated persulfate: Effect of temperature on transformation pathway and product distribution.

    Science.gov (United States)

    Zrinyi, Nick; Pham, Anh Le-Tuan

    2017-09-01

    Heat activates persulfate (S 2 O 8 2- ) into sulfate radical (SO 4 - ), a powerful oxidant capable of transforming a wide variety of contaminants. Previous studies have shown that an increase in temperature accelerates the rates of persulfate activation and contaminant transformation. However, few studies have considered the effect of temperature on contaminant transformation pathway. The objective of this study was to determine how temperature (T = 22-70 °C) influences the activation of persulfate, the transformation of benzoic acid (i.e., a model compound), and the distribution of benzoic acid oxidation products. The time-concentration profiles of the products suggest that benzoic acid was transformed via decarboxylation and hydroxylation mechanisms, with the former becoming increasingly important at elevated temperatures. The pathway through which the products were further oxidized was also influenced by the temperature of persulfate activation. Our findings suggest that the role of temperature in the persulfate-based treatment systems is not limited only to controlling the rates of sulfate and hydroxyl radical generation. The ability of sulfate radical to initiate decarboxylation reactions and, more broadly, fragmentation reactions, as well as the effect of temperature on these transformation pathways could be important to the transformation of a number of organic contaminants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Decomposing the effects of negative framing in linear public goods games.

    OpenAIRE

    Cox, C.

    2015-01-01

    I examine two dimensions of framing in public goods games: Contributing vs. Taking and Gains vs. Losses. I find decreased cooperation under the Taking frame, but not under the Loss frame. This framing effect is stronger for men than women.

  8. Recommendations for international gambling harm-minimisation guidelines: comparison with effective public health policy

    NARCIS (Netherlands)

    Gainsbury, Sally M.; Blankers, Matthijs; Wilkinson, Claire; Schelleman-Offermans, Karen; Cousijn, Janna

    2014-01-01

    Problem gambling represents a significant public health problem, however, research on effective gambling harm-minimisation measures lags behind other fields, including other addictive disorders. In recognition of the need for consistency between international jurisdictions and the importance of

  9. Recommendations for international gambling harm-minimisation guidelines : comparison with effective public health policy

    NARCIS (Netherlands)

    Gainsbury, Sally M; Blankers, Matthijs; Wilkinson, Claire; Schelleman-Offermans, Karen; Cousijn, Janna

    2014-01-01

    Problem gambling represents a significant public health problem, however, research on effective gambling harm-minimisation measures lags behind other fields, including other addictive disorders. In recognition of the need for consistency between international jurisdictions and the importance of

  10. Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in cholestasis and intervention effect of Paeonia lactiflora Pall.

    Directory of Open Access Journals (Sweden)

    Xiao eMa

    2016-02-01

    Full Text Available Background: The dried root of Paeonia lactiflora Pall. (PLP is a classical Chinese herbal medicine that has been used to treat hepatic disease for thousands of years. Our previous work suggested that PLP can be used to treat hepatitis with severe cholestasis. This study explored the mechanism by which PLP affects ANIT-induced cholestasis in rats using a metabolomics approach.Methods: The effects of PLP on serum indices (TBIL, DBIL, AST, ALT, ALP and TBA and the histopathology of the liver were analyzed. Moreover, UHPLC-Q-TOF was performed to identify the possible effect of PLP on metabolites. The pathway analysis was conducted to illustrate the pathways and network by which PLP treats cholestasis. Result: High-dose PLP remarkably down-regulated the serum indices and alleviated histological damage to the liver. Metabolomics analyses showed that the therapeutic effect of high-dose PLP is mainly associated with the regulation of several metabolites, such as glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, L(D-arginine and L-tryptophan. A pathway analysis showed that the metabolites were related to bile acid secretion and amino acid metabolism. In addition, the significant changes in bile acid transporters also indicated that bile acid metabolism might be involved in the therapeutic effect of PLP on cholestasis. Moreover, a principal component analysis indicated that the metabolites in the high-dose PLP group were closer to those of the control, whereas those of the moderate dose or low-dose PLP group were closer to those of the ANIT group. This finding indicated that metabolites may be responsible for the differences between the effects of low-dose and moderate-dose PLP. Conclusions: The therapeutic effect of high-dose PLP on cholestasis is possibly related to regulation of bile acid secretion and amino acid metabolism. Moreover, these findings may help better understand the mechanisms of disease and provide a potential therapy for

  11. Antiproliferative effect of growth hormone-releasing hormone (GHRH antagonist on ovarian cancer cells through the EGFR-Akt pathway

    Directory of Open Access Journals (Sweden)

    Varga Jozsef

    2010-05-01

    Full Text Available Abstract Background Antagonists of growth hormone-releasing hormone (GHRH are being developed for the treatment of various human cancers. Methods MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR. Results In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR level and the phosphorylation of Akt (p-Akt, suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells. Conclusions The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells.

  12. Communicating climate change: Improving the effectiveness of public campaigns

    Directory of Open Access Journals (Sweden)

    María del Carmen Hidalgo Villodres

    2014-08-01

    Full Text Available Research on climate change highlights the need to develop more effective campaigns to increase citizens’ awareness of this issue, increase their willingness to accept the measures necessary to halt this phenomenon and change their behaviour. This paper describes a study which analyzed the effectiveness of an advertising message that combined informative and motivational variables on pro-environmental attitudes and intended behaviour. The study sample consisted of 180 university students, divided into two equivalent groups. The results supported the initial hypothesis,the participants in the group that received specific behaviour guidelines (to increase perceived control together with information on economic savings (motivational variable displayed more changes in self-efficacy, pro-environmental attitudes and intention of behaviour than the group that did not receive this information.

  13. Assessing the effect of public policy on worker absenteeism

    OpenAIRE

    Johansson, Per; Palme, Mårten

    2001-01-01

    We analyze the effect of economic incentives on worker absenteeism, using panel data on work absence for 1990 and 1991 with a sample of 1,396 Swedish blue-collar workers. During this period Sweden implemented major reforms of both its national income replacement program for short-term sickness and income taxes. Both affected the worker's cost of missing work. Our econometric model allows for state-dependent dynamic behavior and control for unobserved heterogeneity. The latter proves to be an ...

  14. Tax Havens and Effective Tax Rates: An Analysis of Private versus Public European Firms

    OpenAIRE

    Aziz Jaafar; John Thorton

    2015-01-01

    We examine the impact of tax-haven operations on the effective corporate tax burdens of publicly listed and privately held firms domiciled in Europe. In particular, we consider how European firmsÕ tax haven operations interacts with factors such listing status and home-country tax reporting systems to determine the relative tax burdens of publicly listed and private firms. Our main empirical results show that tax haven operations is associated with lower effective tax rates for both private a...

  15. A concise guide to effective management of the public works equipment fleet

    OpenAIRE

    De Armas, Vicente.

    1996-01-01

    CIVINS (Civilian Institutions) Thesis document Approved for public release ; distribution is unlimited The purpose of this report is to present in a concise form the principles and fundamentals of managing the public works equipment fleet, providing a basis from which to develop an effective fleet management program. The report begins with a review of today's trends in fleet management, including, organization, privatization, effects of environmental regulations and a discussion on info...

  16. 76 FR 22414 - Amended Proposed Withdrawal, Notice of Public Meetings, Partial Termination of Segregative Effect...

    Science.gov (United States)

    2011-04-21

    ... Withdrawal, Notice of Public Meetings, Partial Termination of Segregative Effect; Arizona, California... the proposed SEZs to include some additional lands. It also terminates the segregative effect as to... proposal is cancelled and the segregative effect established by the June 30, 2009, Notice of Proposed...

  17. Deuterium isotope effects during formation of phenols by hepatic monoxygenases. Evidence for an alternative to the arene oxide pathway

    International Nuclear Information System (INIS)

    Tomaszewski, J.E.; Jerina, D.M.; Daly, J.W.

    1975-01-01

    The in vivo and in vitro metabolisms of normal and deuterated aromatic substrates have been investigated in rats. Significant isotope effects (k/ sub H//k/sub D/ equals 1.3-1.75) were associated with in vivo formation of meta-hydroxylated metabolites from 1:1 mixtures of normal and perdeuterio-(arylring) nitrobenzene, methyl phenyl sulfide, and methyl phenyl sulfone. Since isotope effects of this magnitude are incompatible with arene oxides as intermediates in the formation of phenols, the results provide evidence that multiple pathways are responsible for the formation of phenols in mammals. Significant isotope effects were not associated with the formation of the other phenolic isomers of nitrobenzene, methyl phenyl sulfone, or methyl phenyl sulfide or with the formation of phenolic products from anisole, bromobenzene, chlorobenzene, fluorobenzene, benzonitrile, naphthalene, zoxazolamine, acetanilide, biphenyl, diphenylhydantoin, benzene, o- and p-xylene, toluene, and mesitylene. Significant isotope effects might not be observable with the latter substrates if the kinetic parameters for oxidation of substrate change or if the arene oxide pathway greatly predominates. Furthermore, extensive in vivo metabolism of any substrate would make isotope effects unobservable by the procedure employed, namely the analysis of isotope content in metabolites formed from 1:1 mixtures of normal and deuterated substrates. (U.S.)

  18. Relevance of DNA repair pathways on ascorbic acid effects on Echerichia Coli K-12 cells

    International Nuclear Information System (INIS)

    Slyus, M.A. van; Oliveira, R.L.B. da C.; Felzenszwalb, I.; Gomes, R.A.; Menck, C.F.

    1985-01-01

    Inactivation kinetics were performed with repair proficient and deficient Escherichia coli K-12 cells treated with oxidized solutions of ascorbic acid. The repair pathways controlled by the recA and uvrA gene products are essential for cell survival to the treatment. However, SOS chromotest result indicates that the SOS functions are only induced at high and toxic concentrations of the drug. Moreover, single strand breaks in DNA from treated cells are detected, demonstrating genome damage promoted by oxidized solutions of ascorbate. (M.A.C.) [pt

  19. Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) to Monitor Compound Effects on Cardiac Myocyte Signaling Pathways.

    Science.gov (United States)

    Guo, Liang; Eldridge, Sandy; Furniss, Mike; Mussio, Jodie; Davis, Myrtle

    2015-09-01

    There is a need to develop mechanism-based assays to better inform risk of cardiotoxicity. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are rapidly gaining acceptance as a biologically relevant in vitro model for use in drug discovery and cardiotoxicity screens. Utilization of hiPSC-CMs for mechanistic investigations would benefit from confirmation of the expression and activity of cellular pathways that are known to regulate cardiac myocyte viability and function. This unit describes an approach to demonstrate the presence and function of signaling pathways in hiPSC-CMs and the effects of treatments on these pathways. We present a workflow that employs protocols to demonstrate protein expression and functional integrity of signaling pathway(s) of interest and to characterize biological consequences of signaling modulation. These protocols utilize a unique combination of structural, functional, and biochemical endpoints to interrogate compound effects on cardiomyocytes. Copyright © 2015 John Wiley & Sons, Inc.

  20. Effects of andrographolide on postoperative cognitive dysfunction and the association with NF-κB/MAPK pathway.

    Science.gov (United States)

    Ding, Yongbo; Shi, Cunxian; Chen, Linjing; Ma, Piliang; Li, Kezhong; Jin, Jin; Zhang, Qingfeng; Li, Aizhi

    2017-12-01

    The present study investigated the effects of andrographolide on postoperative cognitive dysfunction (POCD) in aged rats to gain insight of the underlying mechanism, which may provide theoretical basis for the clinical application of andrographolide to prevent POCD in older patients. Thirty aged male rats were randomly assigned to 3 groups: Control, model and andrographolide groups. The Morris water maze test was used to examine the spatial memory and learning ability of the rats postoperatively. The histological alterations of neuronal cells in the hippocampus were visualized by H&E staining. The serum levels of neuron-specific enolase (NSE), human soluble protein-100β (S-100β) and the inflammation factors of interluekin (IL)-1β, IL-6 and TNF-α involved in the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway were detected by ELISA. The NF-κB/MAPK signaling pathway-associated proteins in rat serum were detected by western blotting. Following andrographolide treatment, the rats significantly gained learning ability after surgery. Is it ameliorated hippocampal neuronal injury in rats following surgery. Andrographolide decreased NSE, S-100β, and the inflammation factors, IL-6, IL-1β and TNF-α in serum. Andrographolide reduced NF-κB/MAPK pathway-associated protein expression. Andrographolide ameliorated POCD in aged rats following surgery. The underlying mechanism may be associated with the downregulation the inflammatory factors and NF-κB/MAPK-associated protein expression.

  1. The regulation effect of STAT 5 signaling pathway on the cell cycle progression of irradiated KG-1 cells

    International Nuclear Information System (INIS)

    Guo Dehuang; Dong Bo; Luo Qingliang; Wen Gengyun; Mao Bingzhi

    2000-01-01

    The author investigated the role of the JAK/STAT signaling pathway regulating cell cycle progression in the irradiated KG-1 cells. By permanent transfecting the cells with DN-STAT 5 cDNA to block the JAK/STAT signaling pathway and then transient transfecting with cyclin D 1 or cyclin B 1 cDNA, the effects of cyclin D 1 protein and cyclin B 1 protein on the cell cycle progression were examined. Results showed that after irradiation with 8Gy 60 Co rays, the irradiated KG-1 cells transfected with only DN-STAT 5 cDNA can not recover form the G 1 arrest, even though GM-CSF was added. Meanwhile, the cells transfected with both the DN-STAT 5 cDNA and cyclin D 1 cDNA or cyclin B 1 cDNA can recover from the G 1 arrest or the G 2 arrest to a great extent. Thus, it was proved indirectly that the JAK/STAT signaling pathway activated by GM-CSF regulated the cell cycle progression through cyclin D 1 and cyclin B 1 protein

  2. Differential effects of multiplicity of infection on Helicobacter pylori-induced signaling pathways and interleukin-8 gene transcription.

    Science.gov (United States)

    Ritter, Birgit; Kilian, Petra; Reboll, Marc Rene; Resch, Klaus; DiStefano, Johanna Kay; Frank, Ronald; Beil, Winfried; Nourbakhsh, Mahtab

    2011-02-01

    Interleukin-8 (IL-8) plays a central role in the pathogenesis of Helicobacter pylori infection. We used four different H. pylori strains isolated from patients with gastritis or duodenal ulcer disease to examine their differential effects on signaling pathways and IL-8 gene response in gastric epithelial cells. IL-8 mRNA level is elevated in response to high (100) multiplicity of infection (MOI) independent of cagA, vacA, and dupA gene characteristics. By lower MOIs (1 or 10), only cagA ( + ) strains significantly induce IL-8 gene expression. This is based on differential regulation of IL-8 promoter activity. Analysis of intracellular signaling pathways indicates that H. pylori clinical isolates induce IL-8 gene transcription through NF-κB p65, but by a MOI-dependent differential activation of MAPK pathways. Thus, the major virulence factors of H. pylori CagA, VacA, and DupA might play a minor role in the level of IL-8 gene response to a high bacterial load.

  3. Effects of Ghrelin miRNA on Inflammation and Calcium Pathway in Pancreatic Acinar Cells of Acute Pancreatitis.

    Science.gov (United States)

    Tang, Xiping; Tang, Guodu; Liang, Zhihai; Qin, Mengbin; Fang, Chunyun; Zhang, Luyi

    The study investigated the effects of endogenous targeted inhibition of ghrelin gene on inflammation and calcium pathway in an in vitro pancreatic acinar cell model of acute pancreatitis. Lentiviral expression vector against ghrelin gene was constructed and transfected into AR42J cells. The mRNA and protein expression of each gene were detected by reverse transcription polymerase chain reaction, Western blotting, or enzyme-linked immunosorbent assay. The concentration of intracellular calcium ([Ca]i) was determined by calcium fluorescence mark probe combined with laser scanning confocal microscopy. Compared with the control group, cerulein could upregulate mRNA and protein expression of inflammatory factors, calcium pathway, ghrelin, and [Ca]i. mRNA and protein expression of inflammatory factors increased significantly in cells transfected with ghrelin miRNA compared with the other groups. Intracellular calcium and expression of some calcium pathway proteins decreased significantly in cells transfected with ghrelin miRNA compared with the other groups. Targeted inhibition of ghrelin gene in pancreatic acinar cells of acute pancreatitis can upregulate the expression of the intracellular inflammatory factors and alleviate the intracellular calcium overload.

  4. Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells

    International Nuclear Information System (INIS)

    Luce, A.; Courtin, A.; Levalois, C.; Altmeyer-Morel, S.; Chevillard, S.; Lebeau, J.; Romeo, P.H.

    2009-01-01

    Delayed cell death by mitotic catastrophe is a frequent mode of solid tumor cell death after γ-irradiation, a widely used treatment of cancer. Whereas the mechanisms that underlie the early γ-irradiation-induced cell death are well documented, those that drive the delayed cell death are largely unknown. Here we show that the Fas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and tumor necrosis factor (TNF)-α death receptor pathways mediate the delayed cell death observed after γ-irradiation of breast cancer cells. Early after irradiation, we observe the increased expression of Fas, TRAIL-R and TNF-R that first sensitizes cells to apoptosis. Later, the increased expression of FasL, TRAIL and TNF-α permit the apoptosis engagement linked to mitotic catastrophe. Treatments with TNF-α, TRAIL or anti-Fas antibody, early after radiation exposure, induce apoptosis, whereas the neutralization of the three death receptors pathways impairs the delayed cell death. We also show for the first time that irradiated breast cancer cells excrete soluble forms of the three ligands that can induce the death of sensitive bystander cells. Overall, these results define the molecular basis of the delayed cell death of irradiated cancer cells and identify the death receptors pathways as crucial actors in apoptosis induced by targeted as well as non-targeted effects of ionizing radiation. (authors)

  5. The effect of S1P receptor signaling pathway on the survival and drug resistance in multiple myeloma cells.

    Science.gov (United States)

    Fu, Di; Li, Yingchun; Li, Jia; Shi, Xiaoyan; Yang, Ronghui; Zhong, Yuan; Wang, Huihan; Liao, Aijun

    2017-01-01

    Multiple myeloma (MM) remains incurable by conventional chemotherapy. Sphingosine-1-phosphate (S1P) receptor-mediated signaling has been recently demonstrated to have critical roles in cell survival and drug resistance in a number of hematological malignancies. To dissect the roles of S1P receptor pathway in MM, we systematically examined cell viability and protein expression associated with cell survival and drug resistance in MM cell lines upon treatment with either pathway activator (S1P) or inhibitor (FTY720). Our results reveal that FTY720 inhibits cell proliferation by downregulating expression of target genes, while S1P has an opposite effect. Knocking down of S1P receptor S1P5R results in a reduction of cell survival-related gene expression; however, it does not have impacts on expression of drug resistance genes. These results suggest that S1P signaling plays a role in cell proliferation and drug resistance in MM, and targeting this pathway will provide a new therapeutic direction for MM management.

  6. The long-term effects of maternal depression: early childhood physical health as a pathway to offspring depression.

    Science.gov (United States)

    Raposa, Elizabeth; Hammen, Constance; Brennan, Patricia; Najman, Jake

    2014-01-01

    Cross-sectional and retrospective studies have highlighted the long-term negative effects of maternal depression on offspring physical, social, and emotional development, but longitudinal research is needed to clarify the pathways by which maternal depression during pregnancy and early childhood affects offspring outcomes. The current study tested one developmental pathway by which maternal depression during pregnancy might negatively impact offspring mental health in young adulthood, via poor physical health in early childhood. The sample consisted of 815 Australian youth and their mothers who were followed for 20 years. Mothers reported on their own depressive symptoms during pregnancy and offspring early childhood. Youth completed interviews about health-related stress and social functioning at age 20 years, and completed a questionnaire about their own depressive symptoms 2 to 5 years later. Path analysis indicated that prenatal maternal depressive symptoms predicted worse physical health during early childhood for offspring, and this effect was partially explained by ongoing maternal depression in early childhood. Offspring poor physical health during childhood predicted increased health-related stress and poor social functioning at age 20. Finally, increased health-related stress and poor social functioning predicted increased levels of depressive symptoms later in young adulthood. Maternal depression had a significant total indirect effect on youth depression via early childhood health and its psychosocial consequences. Poor physical health in early childhood and its effects on young adults' social functioning and levels of health related stress is one important pathway by which maternal depression has long-term consequences for offspring mental health. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  7. Global effects of the CSR-1 RNA interference pathway on transcriptional landscape

    Science.gov (United States)

    Cecere, Germano; Hoersch, Sebastian; O’Keeffe, Sean; Sachidanandam, Ravi; Grishok, Alla

    2014-01-01

    Argonaute proteins and their small RNA co-factors short interfering RNAs (siRNAs) are known to inhibit gene expression at the transcriptional and post-transcriptional levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of endogenous siRNAs (endo-siRNAs) antisense to germline transcripts and associates with chromatin in a siRNA-dependent manner. However, its role in gene expression regulation remains controversial. Here, we used a genome-wide profiling of nascent RNA transcripts to demonstrate that the CSR-1 RNAi pathway promotes sense-oriented Pol II transcription. Moreover, a loss of CSR-1 function resulted in global increase in antisense transcription and ectopic transcription of silent chromatin domains, which led to reduced chromatin incorporation of centromere-specific histone H3. Based on these findings, we propose that the CSR-1 pathway has a role in maintaining the directionality of active transcription thereby propagating the distinction between transcriptionally active and silent genomic regions. PMID:24681887

  8. Rapid effects of hearing song on catecholaminergic activity in the songbird auditory pathway.

    Directory of Open Access Journals (Sweden)

    Lisa L Matragrano

    Full Text Available Catecholaminergic (CA neurons innervate sensory areas and affect the processing of sensory signals. For example, in birds, CA fibers innervate the auditory pathway at each level, including the midbrain, thalamus, and forebrain. We have shown previously that in female European starlings, CA activity in the auditory forebrain can be enhanced by exposure to attractive male song for one week. It is not known, however, whether hearing song can initiate that activity more rapidly. Here, we exposed estrogen-primed, female white-throated sparrows to conspecific male song and looked for evidence of rapid synthesis of catecholamines in auditory areas. In one hemisphere of the brain, we used immunohistochemistry to detect the phosphorylation of tyrosine hydroxylase (TH, a rate-limiting enzyme in the CA synthetic pathway. We found that immunoreactivity for TH phosphorylated at serine 40 increased dramatically in the auditory forebrain, but not the auditory thalamus and midbrain, after 15 min of song exposure. In the other hemisphere, we used high pressure liquid chromatography to measure catecholamines and their metabolites. We found that two dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, increased in the auditory forebrain but not the auditory midbrain after 30 min of exposure to conspecific song. Our results are consistent with the hypothesis that exposure to a behaviorally relevant auditory stimulus rapidly induces CA activity, which may play a role in auditory responses.

  9. Developing public health performance measures to capture the effects of transportation facilities on multiple public health outcomes.

    Science.gov (United States)

    2016-04-15

    Increasingly, federal transportation and public health agencies are working together to identify : transportation investments that improve public health. Investments in transportation : infrastructure represent one method to utilize transportation to...

  10. A pivotal role of the jasmonic acid signal pathway in mediating radiation-induced bystander effects in Arabidopsis thaliana.

    Science.gov (United States)

    Wang, Ting; Xu, Wei; Deng, Chenguang; Xu, Shaoxin; Li, Fanghua; Wu, Yuejin; Wu, Lijun; Bian, Po

    Although radiation-induced bystander effects (RIBE) in Arabidopsis thaliana have been well demonstrated in vivo, little is known about their underlying mechanisms, particularly with regard to the participating signaling molecules and signaling pathways. In higher plants, jasmonic acid (JA) and its bioactive derivatives are well accepted as systemic signal transducers that are produced in response to various environmental stresses. It is therefore speculated that the JA signal pathway might play a potential role in mediating radiation-induced bystander signaling of root-to-shoot. In the present study, pretreatment of seedlings with Salicylhydroxamic acid, an inhibitor of lipoxigenase (LOX) in JA biosynthesis, significantly suppressed RIBE-mediated expression of the AtRAD54 gene. After root irradiation, the aerial parts of A. thaliana mutants deficient in JA biosynthesis (aos) and signaling cascades (jar1-1) showed suppressed induction of the AtRAD54 and AtRAD51 genes and TSI and 180-bp repeats, which have been extensively used as endpoints of bystander genetic and epigenetic effects in plants. These results suggest an involvement of the JA signal pathway in the RIBE of plants. Using the root micro-grafting technique, the JA signal pathway was shown to participate in both the generation of bystander signals in irradiated root cells and radiation responses in the bystander aerial parts of plants. The over-accumulation of endogenous JA in mutant fatty acid oxygenation up-regulated 2 (fou2), in which mutation of the Two Pore Channel 1 (TPC1) gene up-regulates expression of the LOX and allene oxide synthase (AOS) genes, inhibited RIBE-mediated expression of the AtRAD54 gene, but up-regulated expression of the AtKU70 and AtLIG4 genes in the non-homologous end joining (NHEJ) pathway. Considering that NHEJ is employed by plants with increased DNA damage, the switch from HR to NHEJ suggests that over-accumulation of endogenous JA might enhance the radiosensitivity of plants

  11. Consumption value theory and the marketing of public health: an effective formative research tool.

    Science.gov (United States)

    Nelson, Douglas G; Byus, Kent

    2002-01-01

    Contemporary public health requires the support and participation of its constituency. This study assesses the capacity of consumption value theory to identify the basis of this support. A telephone survey design used simple random sampling of adult residents of Cherokee County, Oklahoma. Factor analysis and stepwise discriminant analysis was used to identify and classify personal and societal level support variables. Most residents base societal level support on epistemic values. Direct services clientele base their support on positive emotional values derived from personal contact and attractive programs. Residents are curious about public health and want to know more about the health department. Where marketing the effectiveness of public health programs would yield relatively little support, marketing health promotion activities may attract public opposition. This formative research tool suggests a marketing strategy for public health practitioners.

  12. Understanding Autoimmune Mechanisms in Multiple Sclerosis Using Gene Expression Microarrays: Treatment Effect and Cytokine-related Pathways

    Directory of Open Access Journals (Sweden)

    A. Achiron

    2004-01-01

    Full Text Available Multiple sclerosis (MS is a central nervous system disease in which activated autoreactive T-cells invade the blood brain barrier and initiate an inflammatory response that leads to myelin destruction and axonal loss. The etiology of MS, as well as the mechanisms associated with its unexpected onset, the unpredictable clinical course spanning decades, and the different rates of progression leading to disability over time, remains an enigma. We have applied gene expression microarrays technology in peripheral blood mononuclear cells (PBMC to better understand MS pathogenesis and better target treatment approaches. A signature of 535 genes were found to distinguish immunomodulatory treatment effects between 13 treated and 13 untreated MS patients. In addition, the expression pattern of 1109 gene transcripts that were previously reported to significantly differentiate between MS patients and healthy subjects were further analyzed to study the effect of cytokine-related pathways on disease pathogenesis. When relative gene expression for 26 MS patients was compared to 18 healthy controls, 30 genes related to various cytokine-associated pathways were identified. These genes belong to a variety of families such as interleukins, small inducible cytokine subfamily and tumor necrosis factor ligand and receptor. Further analysis disclosed seven cytokine-associated genes within the immunomodulatory treatment signature, and two cytokine-associated genes SCYA4 (small inducible cytokine A4 and FCAR (Fc fragment of IgA, CD89 that were common to both the MS gene expression signature and the immunomodulatory treatment gene expression signature. Our results indicate that cytokine-associated genes are involved in various pathogenic pathways in MS and also related to immunomodulatory treatment effects.

  13. Adverse effects of MWCNTs on life parameters, antioxidant systems, and activation of MAPK signaling pathways in the copepod Paracyclopina nana.

    Science.gov (United States)

    Kim, Duck-Hyun; Puthumana, Jayesh; Kang, Hye-Min; Lee, Min-Chul; Jeong, Chang-Bum; Han, Jeonghoon; Hwang, Dae-Sik; Kim, Il-Chan; Lee, Jin Wuk; Lee, Jae-Seong

    2016-10-01

    Engineered multi-walled carbon nanotubes (MWCNTs) have received widespread applications in a broad variety of commercial products due to low production cost. Despite their significant commercial applications, CNTs are being discharged to aquatic ecosystem, leading a threat to aquatic life. Thus, we investigated the adverse effect of CNTs on the marine copepod Paracyclopina nana. Additional to the study on the uptake of CNTs and acute toxicity, adverse effects on life parameters (e.g. growth, fecundity, and size) were analyzed in response to various concentrations of CNTs. Also, as a measurement of cellular damage, oxidative stress-related markers were examined in a time-dependent manner. Moreover, activation of redox-sensitive mitogen-activated protein kinase (MAPK) signaling pathways along with the phosphorylation pattern of extracellular signal-regulated kinase (ERK), p38, and c-Jun-N-terminal kinases (JNK) were analyzed to obtain a better understanding of molecular mechanism of oxidative stress-induced toxicity in the copepod P. nana. As a result, significant inhibition on life parameters and evoked antioxidant systems were observed without ROS induction. In addition, CNTs activated MAPK signaling pathway via ERK, suggesting that phosphorylated ERK (p-ERK)-mediated adverse effects are the primary cause of in vitro and in vivo endpoints in response to CNTs exposure. Moreover, ROS-independent activation of MAPK signaling pathway was observed. These findings will provide a better understanding of the mode of action of CNTs on the copepod P. nana at cellular and molecular level and insight on possible ecotoxicological implications in the marine environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. The Effectiveness of Integrated Care Pathways for Adults and Children in Health Care Settings: A Systematic Review.

    Science.gov (United States)

    Allen, Davina; Gillen, Elizabeth; Rixson, Laura

    's realistic evaluation methodology. The underlying rationale for this approach is that if we know and understand how different interventions produce varying effects in different circumstances, we are better able to decide what policies/services to implement in what conditions. To identify the purposes for which ICPs are effective, for whom and in what contexts;To identify the purposes for which ICPs are not effective, for whom and in what contexts;To produce recommendations on how ICPs should be used in the full range of health care settings. Types of participants - The review focused on adults and children that accessed health care settings in which ICPs are used.Types of intervention(s)/phenomena of interest - For the purposes of the review, the ICP had to meet the defining characteristics set by the European Pathway Association (EPA):An explicit statement of the goals and key elements of care based on evidence, best practice and patient expectations;Facilitation of communication, coordination of roles, and sequencing of activities of the multidisciplinary care team, patients and their relatives;The documentation, monitoring, and evaluation of variances and outcomes;The identification of the appropriate resources.Here multidisciplinary is taken to refer to the involvement of two or more disciplines.Types of outcomes - Outcome measures were determined by the purposes of the studies selected for review and the type of study participant. Specific clinical outcomes were determined by the group of patients for which the ICP was developed.Types of studies - To address the aims of the review it was necessary to examine evidence of ICP effectiveness across the full spectrum of contexts in which they are in use. In order to keep the study to a manageable scale we limited its scope to randomised controlled trials (RCTs). All RCTs reported between 1980 and 2008 (March) were included in the review. The search was restricted to publications after 1980 coinciding with the emergence of

  15. Examining a pathway for hormone mediated maternal effects - Yolk testosterone affects androgen receptor expression and endogenous testosterone production in young chicks (Gallus gallus domesticus)

    NARCIS (Netherlands)

    Pfannkuche, K. A.; Gahr, M.; Weites, I. M.; Riedstra, B.; Wolf, C.; Groothuis, T. G. G.

    2011-01-01

    In vertebrates maternal androgens can substantially influence developing offspring, inducing both short and long term changes in physiology and behavior, including androgen sensitive traits. However, how the effects of maternal hormones are mediated remains unknown. Two possible pathways are that

  16. Do driving restriction policies effectively motivate commuters to use public transportation?

    International Nuclear Information System (INIS)

    Liu, Yunxia; Hong, Zaisheng; Liu, Yong

    2016-01-01

    Driving restriction policies have been implemented in some large Chinese cities to cope with severe urban smog pollution. We explored the roles of policy acceptance and other factors in commuters' transport mode decisions, based on the Theory of Planned Behavior. A questionnaire survey was conducted in Tianjin, China. A structural equation model was developed to test eight hypotheses, two of which were rejected. The results indicate that a driving restriction policy alone cannot effectively motivate commuters to use public transport if the policymakers fail to improve public transport, enhance commuters' awareness of consequences, increase commuters' perceived behavior control, and encourage car owners to change driving behavior. Comparisons between car owners and non-owners indicated that car owners view driving restriction policy and public transport more negatively. These negative views could be a barrier for the promotion of public transport among car owners. In addition, attitude toward public transport was found to have positive correlation with commuting time. - Highlights: • Attitude towards public transport has an impact on policy acceptance. • Driving habit indirectly affects policy acceptance and perceived behavior control. • Driving restriction policy and public transport are not popular among car owners. • Attitude towards public transport correlates positively with commuting time.

  17. Economic and Environmental Effects of Public Transport Subsidy Policies: a Spatial CGE Model of Beijing

    Directory of Open Access Journals (Sweden)

    Ping Xu

    2018-01-01

    Full Text Available Public transport plays an important role in the environment. This study established a Spatial Computable General Equilibrium (SCGE model to examine the economic and environmental effects of public transport subsidy policies. The model includes firms, consumers, and traffic modules in one framework. Statistical data from Beijing were used in calibration to obtain benchmark equilibrium. Based on the equilibrium, simulations compared citywide social welfare, jobs-housing spatial population distribution, and environmental outputs under four subsidy policies: fare subsidy, cash grants, road expansion, and public transport speedup. Based on the results regarding the effects of public transport policies, conclusions can be drawn about which policies will have greater overall social influence and should therefore be used.

  18. The Effect of “Speak Up” Training Toward Apprehension of Speaking in Front of Public

    OpenAIRE

    Amalia, Rizky Nur; Hidayati, Farida

    2013-01-01

    This study is aimed to evaluate the effect of “SPEAK uP” training toward apprehension of speaking in front of public.The characteristic subject of this study is to students of SMK Negeri 8 Semarang who took social worker studies as their major; mostly they are having apprehension in ability of speaking in front of public with high and extra high category level on apprehension of speaking in front of public, those students had agreed to join “SPEAK uP” training completely. This study generally...

  19. Effective acupuncture practice through diagnosis based on distribution of meridian pathways & related syndromes.

    Science.gov (United States)

    Chen, Yemeng; Zheng, Xin; Li, Hui; Zhang, Qunce; Wang, Tianfang

    2011-01-01

    This article discusses the importance of acupuncture practice utilizing diagnosis and distribution of various meridians and connecting channels based on meridian theory. The meridian system is considered as basic anatomy for acupuncture, so the corresponding pathways and related syndromes of different channels should play a key role in differentiation, known as meridian-related pattern differentiation. Since this doctrine originated in ancient times and was not so well developed in later generations, many acupuncturists are not able to utilize it efficiently. The authors survey how this doctrine was weakened during the past century, especially in acupuncture education for foreigners, and how this important method is currently being reinvigorated. This article also lays out the ways this doctrine can be applied clinically and introduces examples of a variety of indications including some difficult cases, such as whiplash injury, intervertebral disc herniation, oculomotor nerve paralysis, and eczema, etc.

  20. EGb 761 Protects Cardiac Microvascular Endothelial Cells against Hypoxia/Reoxygenation Injury and Exerts Inhibitory Effect on the ATM Pathway.

    Science.gov (United States)

    Zhang, Chao; Wang, Deng-Feng; Zhang, Zhuang; Han, Dong; Yang, Kan

    2017-03-28

    Ginkgo bilob a extract (EGb 761) has been widely used clinically to reduce myocardial ischemia reperfusion injury (MIRI). Microvascular endothelial cells (MVECs) may be a proper cellular model in vitro for the effect and mechanism study against MIRI. However, the protective effect of EGb 761 on MVECs resisting hypoxia/reoxygenation (H/R) injury is little reported. In this study, H/R-injured MVECs were treated with EGb 761, and then the cell viability, apoptosis, ROS production, SOD activity, caspase-3 activity, and protein level of ATM, γ-H2AX, p53, and Bax were measured. ATM siRNA was transfected to study the changes of protein in the ATM pathway. EGb 761 presented protective effect on H/R-injured MVECs, with decreasing cell death, apoptosis, and ROS, and elevated SOD activity. Next, EGb 761 could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax in a dose-dependent manner. Moreover, ATM siRNA also could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax. Overall, these findings verify that EGb 761 protects cardiac MVECs from H/R injury, and for the first time, illustrate the influence on the ATM pathway and apoptosis by EGb 761 via dampening ROS.

  1. Synergetic effect of alkaline earth metal oxides and iron oxides on the degradation of hexachlorobenzene and its degradation pathway.

    Science.gov (United States)

    Su, Guijin; Liu, Yexuan; Huang, Linyan; Shi, Yali; Zhang, Aiqian; Zhang, Lixia; Liu, Wenbin; Gao, Lirong; Zheng, Minghui

    2013-01-01

    The degradation of hexachlorobenzene (HCB) was carried out over physical mixtures of a series of alkaline earth metal oxides (MO: M=Mg, Ca, Sr, Ba) and iron oxides with different crystal types (Fe(x)O(y):Fe(2)O(3) or Fe(3)O(4)) at 300°C. These physical mixtures all showed a synergetic effect toward the degradation of HCB. A range of degradation products were identified by various methods, including tri- to penta-chlorobenzenes by gas chromatography/mass spectrometry (GC-MS), tri- to penta-chlorophenols, tetrachlorocatechol (TCC) and tetrachlorohydroquinone (TCHQ) by GC-MS after derivatization, and formic and acetic acids by ion chromatography. Two degradation pathways, hydrodechlorination and oxidative degradation, appear to occur competitively. However, more sequential chlorinated benzene and phenol congeners were formed over mixed MO/Fe(3)O(4) than over mixed MO/Fe(2)O(3) under the same conditions. The oxidative reaction dominated over mixed MO/Fe(2)O(3) and was promoted as the major reaction by the synergetic effect, while both the oxidative and hydrodechlorination reactions were important over mixed MO/Fe(3)O(4), and both pathways are remarkably promoted by the synergetic effect. The enhanced hydrodechlorination may be attributed to free electrons generated by the transformation of Fe(3)O(4) into Fe(2)O(3), and hydrogen provided by water adsorbed on the MO. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. The effect of neutral-surface iron oxide nanoparticles on cellular uptake and signaling pathways

    Directory of Open Access Journals (Sweden)

    Kim E

    2016-09-01

    Full Text Available Eunjoo Kim,1 Joon Mee Kim,2 Lucia Kim,2 Suk Jin Choi,2 In Suh Park,2 Jee Young Han,2 Young Chae Chu,2 Eun Sook Choi,1 Kun Na,3 Soon-Sun Hong4 1Division of Nano and Energy Convergence Research, Daegu Gyeongbuk Institute of Science and Technology (DGIST, Daegu, 2Department of Pathology, Inha University College of Medicine, Incheon, 3Department of Biotechnology, Catholic University of Korea, Bucheon, 4Department of Biomedical Sciences, Inha University College of Medicine, Incheon, South Korea Abstract: In recent years, iron oxide nanoparticles (IONPs have been applied widely to biomedical fields. However, the relationship between the physicochemical properties of IONPs and their biological behavior is not fully understood yet. We prepared 3-methacryloxypropyl­trimethoxysilane (MPS-coated IONPs, which have a neutral hydrophobic surface, and compared their biological behavior to that of Resovist (ferucarbotran, a commercialized IONP formulation modified with carboxymethyl dextran. The rate of MPS-IONP uptake by human aortic endothelial cells (HAoECs was higher than ferucarbotran uptake, indicating that the neutral hydrophobic nature of MPS-IONPs allowed them to be absorbed more readily through the plasma membrane. However, the signaling pathways activated by MPS-IONPs and ferucarbotran were comparable, suggesting that surface charge is not a key factor for inducing changes in HAoECs. In vivo fate analysis showed that MPS-IONPs accumulated for longer periods in tissues than hydrophilic ferucarbotran. These findings could enlarge our understanding of NP behavior for advanced applications in the biomedical field. Keywords: iron oxide nanoparticles, neutral hydrophobic surface, signaling pathway, uptake, accumulation, reactive oxygen species (ROS

  3. Effects of Cellular Pathway Disturbances on Misfolded Superoxide Dismutase-1 in Fibroblasts Derived from ALS Patients.

    Directory of Open Access Journals (Sweden)

    Isil Keskin

    Full Text Available Mutations in superoxide dismutase-1 (SOD1 are a common known cause of amyotrophic lateral sclerosis (ALS. The neurotoxicity of mutant SOD1s is most likely caused by misfolded molecular species, but disease pathogenesis is still not understood. Proposed mechanisms include impaired mitochondrial function, induction of endoplasmic reticulum stress, reduction in the activities of the proteasome and autophagy, and the formation of neurotoxic aggregates. Here we examined whether perturbations in these cellular pathways in turn influence levels of misfolded SOD1 species, potentially amplifying neurotoxicity. For the study we used fibroblasts, which express SOD1 at physiological levels under regulation of the native promoter. The cells were derived from ALS patients expressing 9 different SOD1 mutants of widely variable molecular characteristics, as well as from patients carrying the GGGGCC-repeat-expansion in C9orf72 and from non-disease controls. A specific ELISA was used to quantify soluble, misfolded SOD1, and aggregated SOD1 was analysed by western blotting. Misfolded SOD1 was detected in all lines. Levels were found to be much lower in non-disease control and the non-SOD1 C9orf72 ALS lines. This enabled us to validate patient fibroblasts for use in subsequent perturbation studies. Mitochondrial inhibition, endoplasmic reticulum stress or autophagy inhibition did not affect soluble misfolded SOD1 and in most cases, detergent-resistant SOD1 aggregates were not detected. However, proteasome inhibition led to uniformly large increases in misfolded SOD1 levels in all cell lines and an increase in SOD1 aggregation in some. Thus the ubiquitin-proteasome pathway is a principal determinant of misfolded SOD1 levels in cells derived both from patients and controls and a decline in activity with aging could be one of the factors behind the mid-to late-life onset of inherited ALS.

  4. Therapeutic effect of a novel Wnt pathway inhibitor on cardiac regeneration after myocardial infarction.

    Science.gov (United States)

    Yang, Dezhong; Fu, Wenbin; Li, Liangpeng; Xia, Xuewei; Liao, Qiao; Yue, Rongchuan; Chen, Hongmei; Chen, Xiongwen; An, Songzhu; Zeng, Chunyu; Wang, Wei Eric

    2017-12-15

    After myocardial infarction (MI), the heart is difficult to repair because of great loss of cardiomyoctyes and lack of cardiac regeneration. Novel drug candidates that aim at reducing pathological remodeling and stimulating cardiac regeneration are highly desirable. In the present study, we identified if and how a novel porcupine inhibitor CGX1321 influenced MI and cardiac regeneration. Permanent ligation of left anterior descending (LAD) coronary artery was performed in mice to induce MI injury. Cardiac function was measured by echocardiography, infarct size was examined by TTC staining. Fibrosis was evaluated with Masson's trichrome staining and vimentin staining. As a result, CGX1321 administration blocked the secretion of Wnt proteins, and inhibited both canonical and non-canonical Wnt signaling pathways. CGX1321 improved cardiac function, reduced myocardial infarct size, and fibrosis of post-MI hearts. CGX1321 significantly increased newly formed cardiomyocytes in infarct border zone of post-MI hearts, evidenced by the increased EdU + cardiomyocytes. Meanwhile, CGX1321 increased Ki67 + and phosphohistone H3 (PH3 + ) cardiomyocytes in culture, indicating enhanced cardiomyocyte proliferation. The mRNA microarray showed that CGX1321 up-regulated cell cycle regulating genes such as Ccnb1 and Ccne1 CGX1321 did not alter YAP protein phosphorylation and nuclear translocation in cardiomyocytes. In conclusion, porcupine inhibitor CGX1321 reduces MI injury by limiting fibrosis and promoting regeneration. It promotes cardiomyocyte proliferation by stimulating cell cycle regulating genes with a Hippo/YAP-independent pathway. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  5. „Model of Effective Management of Bulgarian Public Administration Managing EU Funds“

    OpenAIRE

    Nozharov, Shteryo

    2014-01-01

    Abstract: The paper analyzes the possibilities of constructing a model for the effective management of the Bulgarian public administration responsible for managing the EU funds amid the global financial crisis by using McKinsey’s 7S model. The change of the management model of the public administration in charge of the absorption of EU funds in Bulgaria would increase the absorption rate of the funds while streamlining budgetary costs on the maintenance of the administration. The aim of the s...

  6. Informing people about radiation risks: a review of obstacles to public understanding and effective risk communication

    International Nuclear Information System (INIS)

    Covello, V.T.

    1988-01-01

    This paper reviews the literature on informing people about radiation risks. The paper focuses on obstacles to public understanding and effective risk communication. The paper concludes with a set of guidelines for communicating information about radiation risks to the public. The paper also includes an appendix that reviews the literature on one of the most important tools for communicating information about radiation risks: risk comparisons

  7. Promoting public transport as a subscription service: Effects of a free month travel card

    DEFF Research Database (Denmark)

    Thøgersen, John

    2009-01-01

    Newspapers, book clubs, telephone services and many other subscription services are often marketed to new customers by means of a free or substantially discounted trial period. This article evaluates this method as a means to promote commuting by public transport in a field experiment and based...... that had an effect was the free month travel card, which led to a significant increase in commuting by public transport.As expected, the effect was mediated through a change in behavioural intentions rather than a change in perceived constraints. As expected, the effect became weaker when the promotion...

  8. Detrimental Effects of Performance-Related Pay in the Public Sector?

    DEFF Research Database (Denmark)

    Bregn, Kirsten

    2013-01-01

    Performance-related pay has been a key ingredient in New Public Management reforms. Nevertheless, the research presented here indicates some adverse effects of such incentives. These incentives may impair an initial motivation to work and change the norms that guide behavior. An issue which...... in particular has been given insufficient attention is fairness. Findings drawn from experimental economics supported by field studies demonstrate that perceived unfairness may have important negative effects on performance. The implication of a broader perspective in the analysis of performance-related pay...... in the public sector is that such a pay system, contrary to its aim, may have detrimental effects on performance....

  9. Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas

    International Nuclear Information System (INIS)

    Pignochino, Ymera; Bardelli, Alberto; Aglietta, Massimo; Leone, Francesco; Sarotto, Ivana; Peraldo-Neia, Caterina; Penachioni, Junia Y; Cavalloni, Giuliana; Migliardi, Giorgia; Casorzo, Laura; Chiorino, Giovanna; Risio, Mauro

    2010-01-01

    Advanced biliary tract carcinomas (BTCs) have poor prognosis and limited therapeutic options. Therefore, it is crucial to combine standard therapies with molecular targeting. In this study EGFR, HER2, and their molecular transducers were analysed in terms of mutations, amplifications and over-expression in a BTC case series. Furthermore, we tested the efficacy of drugs targeting these molecules, as single agents or in combination with gemcitabine, the standard therapeutic agent against BTC. Immunohistochemistry, FISH and mutational analysis were performed on 49 BTC samples of intrahepatic (ICCs), extrahepatic (ECCs), and gallbladder (GBCs) origin. The effect on cell proliferation of different EGFR/HER2 pathway inhibitors as single agents or in combination with gemcitabine was investigated on BTC cell lines. Western blot analyses were performed to investigate molecular mechanisms of targeted drugs. EGFR is expressed in 100% of ICCs, 52.6% of ECCs, and in 38.5% of GBCs. P-MAPK and p-Akt are highly expressed in ICCs (>58% of samples), and to a lower extent in ECCs and GBCs (<46%), indicating EGFR pathway activation. HER2 is overexpressed in 10% of GBCs (with genomic amplification), and 26.3% of ECCs (half of which has genomic amplification). EGFR or its signal transducers are mutated in 26.5% of cases: 4 samples bear mutations of PI3K (8.2%), 3 cases (6.1%) in K-RAS, 4 (8.2%) in B-RAF, and 2 cases (4.1%) in PTEN, but no loss of PTEN expression is detected. EGI-1 cell line is highly sensitive to gemcitabine, TFK1 and TGBC1-TKB cell lines are responsive and HuH28 cell line is resistant. In EGI-1 cells, combination with gefitinib further increases the antiproliferative effect of gemcitabine. In TFK1 and TGBC1-TKB cells, the efficacy of gemcitabine is increased with addiction of sorafenib and everolimus. In TGBC1-TKB cells, lapatinib also has a synergic effect with gemcitabine. HuH28 becomes responsive if treated in combination with erlotinib. Moreover, HuH28 cells are

  10. No, Virginia, It's Not True What They Say About Publicity's "Implied Third-Party Endorsement" Effect.

    Science.gov (United States)

    Hallahan, Kirk

    1999-01-01

    Re-examines "implied third-party endorsement" as an explanation of publicity's effectiveness. Argues that any effect involves inferences by audience members who use biased processing that favors news and disfavors advertising. Suggests that the presentation of information as news is not necessarily perceived by audiences as an…

  11. Role of hippocampal and prefrontal cortical signaling pathways in dextromethorphan effect on morphine-induced memory impairment in rats.

    Science.gov (United States)

    Ghasemzadeh, Zahra; Rezayof, Ameneh

    2016-02-01

    Evidence suggests that dextromethorphan (DM), an NMDA receptor antagonist, induces memory impairment. Considering that DM is widely used in cough-treating medications, and the co-abuse of DM with morphine has recently been reported, the aims of the present study was (1) to investigate whether there is a functional interaction between morphine and DM in passive avoidance learning and (2) to assess the possible role of the hippocampal and prefrontal cortical (PFC) signaling pathways in the effects of the drugs on memory formation. Our findings indicated that post-training or pre-test administration of morphine (2 and 6 mg/kg) or DM (10-30 mg/kg) impaired memory consolidation and retrieval which was associated with the attenuation of the levels of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II (p-CAMKII) and cAMP responsive element-binding protein (p-CREB) in the targeted sites. Moreover, the memory impairment induced by post-training administration of morphine was reversed by pre-test administration of the same dose of morphine or DM (30 mg/kg), indicating state-dependent learning (SDL) and a cross-SDL between the drugs. It is important to note that the levels of p-CAMKII/CAMKII and p-CREB/CREB in the hippocampus and the PFC increased in drugs-induced SDL. In addition, DM administration potentiated morphine-induced SDL which was related to the enhanced levels of hippocampal and PFC CAMKII-CREB signaling pathways. It can be concluded that there is a relationship between the hippocampus and the PFC in the effect of DM and/or morphine on memory retrieval. Moreover, a cross SDL can be induced between the co-administration of DM and morphine. Interestingly, CAMKII-CREB signaling pathways also mediate the drugs-induced SDL. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Involvement of NO-cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia.

    Science.gov (United States)

    Otari, K V; Upasani, C D

    2015-08-01

    The association of elevated level of cyclic guanosine monophosphate (cGMP) with inhibition of hyperalgesia and involvement of nitric oxide (NO)-cGMP pathway in the modulation of pain perception was previously reported. Phosphodiesterases 5 (PDE5) inhibitors, sildenafil and tadalafil (TAD) used in erectile dysfunction, are known to act via the NO-cGMP pathway. TAD exerts its action by increasing the levels of intracellular cGMP. Hence, the present study investigated the effect of TAD 5, 10, or 20 mg/kg, per os (p.o.) or L-NAME 20 mg/kg, intraperitoneally (i.p.) and TAD (20 mg/kg, p.o.) in carrageenan- and diabetes-induced hyperalgesia in rats using hot plate test at 55 ± 2 °C. In carrageenan- and diabetes-induced hyperalgesia, TAD (10 and 20 mg/kg, p.o.) significantly increased paw withdrawal latencies (PWLs) as compared to the control group. L-NAME significantly decreased PWLs as compared to the normal group and aggravated the hyperalgesia. Moreover, significant difference in PWLs of L-NAME and TAD 20 was evident. Co-administration of L-NAME (20 mg/kg) with TAD (20 mg/kg) showed significant difference in PWLs as compared to the TAD (20 mg/kg), indicating L-NAME reversed and antagonized TAD-induced anti-hyperalgesia. This suggested an important role of NO-cGMP pathway in TAD-induced anti-hyperalgesic effect.

  13. Genes and (Common) Pathways Underlying Drug Addiction

    Science.gov (United States)

    Li, Chuan-Yun; Mao, Xizeng; Wei, Liping

    2008-01-01

    Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn), the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction. PMID:18179280

  14. Genes and (common pathways underlying drug addiction.

    Directory of Open Access Journals (Sweden)

    Chuan-Yun Li

    2008-01-01

    Full Text Available Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn, the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction.

  15. Multi-causal pathways of public opposition to dam projects in Asia: A fuzzy set qualitative comparative analysis (fsQCA)

    NARCIS (Netherlands)

    Kirchherr, Julian; Charles, Katrina J.; Walton, Matthew J.

    2016-01-01

    Scholars overwhelmingly adopt the case study method when analyzing causal conditions inducing anti-dam-protests. We have carried out the first medium-N-study on this topic analyzing public opposition to 12 dam projects in Asia. For this purpose, we employ a fuzzy-set Qualitative Comparative Analysis

  16. The effect of tributyltin chloride on Caenorhabditis elegans germline is mediated by a conserved DNA damage checkpoint pathway.

    Science.gov (United States)

    Cheng, Zhe; Tian, Huimin; Chu, Hongran; Wu, Jianjian; Li, Yingying; Wang, Yanhai

    2014-03-21

    Tributyltin (TBT), one of the environmental pollutants, has been shown to impact the reproduction of animals. However, due to the lack of appropriate animal model, analysis of the affected molecular pathways in germ cells is lagging and has been particularly challenging. In the present study, we investigated the effects of tributyltin chloride (TBTCL) on the nematode Caenorhabditis elegans germline. We show that exposure of C. elegans to TBTCL causes significantly elevated level of sterility and embryonic lethality. TBTCL exposure results in an increased number of meiotic DNA double-strand breaks in germ cells, subsequently leading to activated DNA damage checkpoint. Exposing C. elegans to TBTCL causes dose- and time-dependent germline apoptosis. This apoptotic response was blocked in loss-of-function mutants of hus-1 (op241), mrt-2 (e2663) and p53/cep-1 (gk138), indicating that checkpoints and p53 are essential for mediating TBTCL-induced germ cell apoptosis. Moreover, TBTCL exposure can inhibit germ cell proliferation, which is also mediated by the conserved checkpoint pathway. We thereby propose that TBT exhibits its effects on the germline by inducing DNA damage and impaired maintenance of genomic integrity. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  17. Effect of aspirin and prostaglandins on the carbohydrate metabolism in albino rats.: glucose oxidation through different pathways and glycolytic enzymes

    International Nuclear Information System (INIS)

    Balasubramanian, A.; Ramakrishnan, S.

    1980-01-01

    The effect of chronic and acute doses of aspirin and prostaglandins F2α and E2 individually on the oxidation of glucose through Embden Meyerhof-TCA cycle and pentose phosphate pathways and some key glycolytic enzymes of liver were studied in male albino rats. Studies were extended to find the combined effect of PGF2α and E2 with an acute dose of aspirin. There was increased utilisation of both 1- 14 C glucose and 6- 14 C glucose on aspirin treatment. However, the metabolism through the EM-TCA pathway was more pronounced as shown by a reduced ratio of 14 CO 2 from 1- 14 C and 6- 14 C glucose. Two hepatic key glycolytic enzymes viz. hexokinase and pyruvate kinase were increased due to aspirin treatment. Withdrawal of aspirin corrected the above impaired carbohydrate metabolism in liver. Prostaglandin F2α also caused a reduction in the utilisation of 1- 14 C glucose, while PGE2 recorded an increase in the utilisation of both 1- 14 C and 6- 14 C glucose when compared to controls, indicating that different members of prostaglandins could affect metabolisms and differently. Administration of the PGs and aspirin together showed an increase in the utilisation of 6- 14 C glucose. (auth.)

  18. Protective Effect of Saccharomyces boulardii on Deoxynivalenol-Induced Injury of Porcine Macrophage via Attenuating p38 MAPK Signal Pathway.

    Science.gov (United States)

    Chang, Chao; Wang, Kun; Zhou, Sheng-Nan; Wang, Xue-Dong; Wu, Jin-E

    2017-05-01

    The aims of our study were to evaluate the effects of Saccharomyces boulardii (S. boulardii) on deoxynivalenol (DON)-induced injury in porcine alveolar macrophage cells (PAMCs) and to explore the underlying mechanisms. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis, ELISA, qRT-PCR, and western blot were performed to assess whether S. boulardii could prevent DON-induced injury by p38 mitogen-activated protein kinase (p38 MAPK) signal pathway. The results showed that pretreatment with 8 μM DON could decrease the viability of PAMC and significantly increase the apoptosis rate of PAMC, whereas S. boulardii could rescue apoptotic PAMC cells induced by DON. Further experiments revealed that S. boulardii effectively reversed DON-induced cytotoxicity via downregulating the expression of TNF-α, IL-6, and IL-lβ. In addition, S. boulardii significantly alleviated DON-induced phosphorylation and mRNA expression of p38 and further increased the expression of apoptosis regulation genes Bcl-xl and Bcl-2 and inhibited the activation of Bax. Our results suggest that S. boulardii could suppress DON-induced p38 MAPK pathway activation and reduce the expression of downstream inflammatory cytokines, as well as promote the expression of anti-apoptotic genes to inhibit apoptosis induced by DON in PAMC.

  19. Effects of cortisol and dexamethasone on insulin signalling pathways in skeletal muscle of the ovine fetus during late gestation.

    Directory of Open Access Journals (Sweden)

    Juanita K Jellyman

    Full Text Available Before birth, glucocorticoids retard growth, although the extent to which this is mediated by changes in insulin signalling pathways in the skeletal muscle of the fetus is unknown. The current study determined the effects of endogenous and synthetic glucocorticoid exposure on insulin signalling proteins in skeletal muscle of fetal sheep during late gestation. Experimental manipulation of fetal plasma glucocorticoid concentration was achieved by fetal cortisol infusion and maternal dexamethasone treatment. Cortisol infusion significantly increased muscle protein levels of Akt2 and phosphorylated Akt at Ser473, and decreased protein levels of phosphorylated forms of mTOR at Ser2448 and S6K at Thr389. Muscle GLUT4 protein expression was significantly higher in fetuses whose mothers were treated with dexamethasone compared to those treated with saline. There were no significant effects of glucocorticoid exposure on muscle protein abundance of IR-β, IGF-1R, PKCζ, Akt1, calpastatin or muscle glycogen content. The present study demonstrated that components of the insulin signalling pathway in skeletal muscle of the ovine fetus are influenced differentially by naturally occurring and synthetic glucocorticoids. These findings may provide a mechanism by which elevated concentrations of endogenous glucocorticoids retard fetal growth.

  20. Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer.

    Science.gov (United States)

    Cui, X Y; Tinholt, M; Stavik, B; Dahm, A E A; Kanse, S; Jin, Y; Seidl, S; Sahlberg, K K; Iversen, N; Skretting, G; Sandset, P M

    2016-02-01

    ESSENTIALS: A hypoxic microenvironment is a common feature of tumors that may influence activation of coagulation. MCF-7 and SK-BR-3 breast cancer cells and breast cancer tissue samples were used. The results showed transcriptional repression of tissue factor pathway inhibitor expression in hypoxia. Hypoxia-inducible factor 1α may be a target for the therapy of cancer-related coagulation and thrombosis. Activation of coagulation is a common finding in patients with cancer, and is associated with an increased risk of venous thrombosis. As a hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia-inducible factor (HIF)-1α in breast cancer cells and their correlation in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. Time-dependent and dose-dependent downregulation of TFPI mRNA (quantitative RT-PCR) and of free TFPI protein (ELISA) were observed in hypoxia. Western blotting showed parallel increases in the levels of HIF-1α protein and TF. HIF-1α inhibitor abolished or attenuated the hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and HIF-1α overexpression caused strong repression of TFPI promoter activity. Subsequent chromatin immunoprecipitation and mutagenesis analysis demonstrated a functional hypoxia response element within the TFPI promoter, located at -1065 to -1060 relative to the transcriptional start point. In breast cancer tissue samples, gene expression analyses showed a positive correlation between the mRNA expression of TFPI and that of HIF-1α. This study demonstrates that HIF-1α is involved in the transcriptional regulation of the TFPI gene, and suggests that a hypoxic microenvironment inside a breast tumor may

  1. Effect of temperature on the reaction pathway of calcium carbonate formation via precursor phases

    Science.gov (United States)

    Purgstaller, Bettina; Mavromatis, Vasileios; Konrad, Florian; Dietzel, Martin

    2016-04-01

    It has been earlier postulated that some biogenic and sedimentary calcium carbonate (CaCO3) minerals (e.g. calcite and aragonite) are secondary in origin and have originally formed via a metastable calcium carbonate precursor phase (e.g. amorphous CaCO3, [1-2]). Such formation pathways are likely affected by various physicochemical parameters including aqueous Mg and temperature. In an effort to improve our understanding on the formation mechanism of CaCO3 minerals, precipitation experiments were carried out by the addition of a 0.6 M (Ca,Mg)Cl2 solution at distinct Mg/Ca ratios (1/4 and 1/8) into a 1 M NaHCO3 solution under constant pH conditions(8.3 ±0.1). The formation of CaCO3 was systematically examined as a function of temperature (6, 12, 18 and 25 ±0.3° C). During the experimental runs mineral precipitation was monitored by in situ Raman spectroscopy as well as by continuous sampling and analyzing of precipitates and reactive solutions. The results revealed two pathways of CaCO3 formation depending on the initial Mg/Ca ratio and temperature: (i) In experiments with a Mg/Ca ratio of 1/4 at ≤ 12° C as well as in experiments with a Mg/Ca ratio of 1/8 at ≤ 18° C, ikaite (CaCO3 6H2O) acts as a precursor phase for aragonite formation. (ii) In contrast higher temperatures induced the formation of Mg-rich amorphous CaCO3 (Mg-ACC) which was subsequently transformed to Mg-rich calcite. In situ Raman spectra showed that the transformation of Mg-ACC to Mg-calcite occurs at a higher rate (˜ 8 min) compared to that of ikaite to aragonite (> 2 h). Thus, the formation of aragonite rather than of Mg-calcite occurs due to the slower release of Ca2+and CO32- ions into the Mg-rich reactive solution during retarded ikaite dissolution. This behavior is generally consistent with the observation that calcite precipitation is inhibited at elevated aqueous Mg/Ca ratios. [1] Addadi L., Raz S. and Weiner S. (2003) Advanced Materials 15, 959-970. [2] Rodriguez-Blanco J. D

  2. Effectiveness of public health interventions in food safety: a systematic review.

    Science.gov (United States)

    Campbell, M E; Gardner, C E; Dwyer, J J; Isaacs, S M; Krueger, P D; Ying, J Y

    1998-01-01

    To summarize evidence on the effectiveness of public health interventions regarding food safety at restaurants, institutions, homes and other community-based settings. This systematic review of published and unpublished studies involved a comprehensive literature search, screening for relevance, quality assessment of relevant studies, data extraction and synthesis. The interventions identified in 15 studies included in this review were grouped into three categories: inspections, food handler training, and community-based education. The evidence suggests that: routine inspection (at least once per year) of food service premises is effective in reducing the risk of foodborne illness; food handler training can improve the knowledge and practices of food handlers; and selected community-based education programs can increase public knowledge of food safety. There is some evidence for the effectiveness of multiple public health interventions on food safety. Future research needs include evaluation of HACCP and community-based education programs.

  3. Effects of Public Preschool Expenditures on the Test Scores of 4th Graders: Evidence from TIMSS

    Science.gov (United States)

    Waldfogel, Jane; Zhai, Fuhua

    2011-01-01

    This study examines the effects of public preschool expenditures on the math and science scores of 4th graders, holding constant child, family, and school characteristics, other relevant social expenditures, and country and year effects, in seven Organization for Economic Co-operation and Development (OECD) countries -- Australia, Japan, Netherlands, New Zealand, Norway, U.K., and U.S -- using data from the 1995 and 2003 Trends in International Mathematics and Science Study (TIMSS). Our results indicate that there are small but significant positive effects of public preschool expenditures on the math and science scores of 4th graders and preschool expenditures reduce the risk of children scoring at the low level of proficiency. We also find some evidence that children from low-resource homes and homes where the test language is not always spoken may tend to gain more from increased public preschool expenditures than other children,. PMID:21442008

  4. Effects of Public Preschool Expenditures on the Test Scores of 4 Graders: Evidence from TIMSS.

    Science.gov (United States)

    Waldfogel, Jane; Zhai, Fuhua

    2008-02-01

    This study examines the effects of public preschool expenditures on the math and science scores of 4(th) graders, holding constant child, family, and school characteristics, other relevant social expenditures, and country and year effects, in seven Organization for Economic Co-operation and Development (OECD) countries -- Australia, Japan, Netherlands, New Zealand, Norway, U.K., and U.S -- using data from the 1995 and 2003 Trends in International Mathematics and Science Study (TIMSS). Our results indicate that there are small but significant positive effects of public preschool expenditures on the math and science scores of 4(th) graders and preschool expenditures reduce the risk of children scoring at the low level of proficiency. We also find some evidence that children from low-resource homes and homes where the test language is not always spoken may tend to gain more from increased public preschool expenditures than other children,.

  5. Assessing communications effectiveness in meeting corporate goals of public health organizations.

    Science.gov (United States)

    Brown, Gordon D; Bopp, Kenneth D; Boren, Suzanne Austin

    2005-01-01

    Much evaluation of health communications in public health is considered from a program perspective of smoking cessation, weight reduction, education on sexually transmitted diseases, etc. These studies have advanced the knowledge base of communications theory and evaluation and have contributed to program effectiveness. In program-based evaluation the communications process is structured as part of the program itself. This article extends program-based communications evaluation to view communications from the perspective of the consumer and how effectively public health departments respond to consumer expectations. It develops a conceptual model for evaluating elements of communications such as its importance in defining mission and goals within the community, managing strategic constituencies, and enlisting individuals and groups as customers and co-producers of health. It gives a broader perspective on how communications in public heath organizations are managed and a basis for assessing whether they are being managed effectively.

  6. Overview of the Main Theories on the Economic Effects of Public Indebtedness

    Directory of Open Access Journals (Sweden)

    Irina Bilan

    2016-05-01

    Full Text Available The paper briefly reviews the main theories formulated over time on the economic effects of public indebtedness, with the aim to highlight their common and divergent points, the arguments they rely upon, as well as their relevance, given the current economic environment. Three major views are considered, namely the classical one, the Keynesian one and the view of neoliberal economists (monetarist economists and representatives of the school of rational expectations. The comparative approach of the different views allowed us to shape some criteria of decision which may prove useful for public policymakers in formulating public debt policies conducive to economic growth: public indebtedness should not become common practice but be reserved for those situations in which the economy is confronted with unusual phenomena, such as economic downturns; borrowed resources should be used especially on those destinations which create added value in the economy, such as public investment; public debt should not accumulate at a fast pace and should be kept within reasonable limits, to avoid possible side effects on economic growth.

  7. Effects of pictures and textual arguments in sun protection public service announcements.

    Science.gov (United States)

    Boer, Henk; Ter Huurne, Ellen; Taal, Erik

    2006-01-01

    The effect of public service announcements aimed at promoting primary prevention of skin cancer may be limited by superficial cognitive processing. The use of both pictures and textual arguments in sun protection public service announcements were evaluated for their potentially beneficial effects on judgment, cognitive processing and persuasiveness. In a 2 x 2 factorial experimental design individuals were shown public service announcements that advocated the advantages of sun protection measures in different versions in which a picture was present or not present and a textual argument was present or not present. The 159 participants were randomly assigned to one of four conditions. In each condition, participants were shown 12 different public service announcements designed according to the condition. Participants judged each public service announcement on attractiveness, credibility, clarity of communication and the required amount of reflection. After the judgment task, they completed a questionnaire to assess knowledge, perceived advantages and disadvantages of sun protection and intended use of sun protection measures. Pictures enhanced attractiveness, but diminished comprehension. Textual arguments enhanced attractiveness, credibility and comprehension. Pictures as well as textual arguments increased knowledge of sun protection measures. Pictures and textual arguments in public service announcements positively influence the individual's perception of the advantages of sun protection methods and the advantages of their adoption.

  8. The Protective Effect of Gangliosides on Lead (Pb)-Induced Neurotoxicity Is Mediated by Autophagic Pathways.

    Science.gov (United States)

    Meng, Hongtao; Wang, Lan; He, Junhong; Wang, Zhufeng

    2016-03-25

    Lead (Pb) is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS) from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions.

  9. The Protective Effect of Gangliosides on Lead (Pb-Induced Neurotoxicity Is Mediated by Autophagic Pathways

    Directory of Open Access Journals (Sweden)

    Hongtao Meng

    2016-03-01

    Full Text Available Lead (Pb is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions.

  10. Pleiotrophin Exerts Its Migration and Invasion Effect through the Neuropilin-1 Pathway

    Directory of Open Access Journals (Sweden)

    Rania Elahouel

    2015-08-01

    Full Text Available Pleiotrophin (PTN is a pleiotropic growth factor that exhibits angiogenic properties and is involved in tumor growth and metastasis. Although it has been shown that PTN is expressed in tumor cells, few studies have investigated its receptors and their involvement in cell migration and invasion. Neuropilin-1 (NRP-1 is a receptor for multiple growth factors that mediates cell motility and plays an important role in angiogenesis and tumor progression. Here we provide evidence for the first time that NRP-1 is crucial for biological activities of PTN. We found that PTN interacted directly with NRP-1 through its thrombospondin type-I repeat domains. Importantly, binding of PTN to NRP-1 stimulated the internalization and recycling of NRP-1 at the cell surface. Invalidation of NRP-1 by RNA interference in human carcinoma cells inhibited PTN-induced intracellular signaling of the serine-threonine kinase, mitogen-activated protein MAP kinase, and focal adhesion kinase pathways. Accordingly, NRP-1 silencing or blocking by antibody inhibited PTN-induced human umbilical vein endothelial cell migration and tumor cell invasion. These results suggest that NRP-1/PTN interaction provides a novel mechanism for controlling the response of endothelial and tumoral cells to PTN and may explain, at least in part, how PTN contributes to tumor angiogenesis and cancer progression.

  11. Expert elicitation on ultrafine particles: likelihood of health effects and causal pathways.

    NARCIS (Netherlands)

    Knol, A.B.; de Hartog, J.J.|info:eu-repo/dai/nl/288354850; Boogaard, H.|info:eu-repo/dai/nl/314406522; Slottje, P.|info:eu-repo/dai/nl/299345351; van der Sluijs, J.P.|info:eu-repo/dai/nl/073427489; Lebret, E.|info:eu-repo/dai/nl/071318917; Cassee, F.R.|info:eu-repo/dai/nl/143038990; Wardekker, J.A.|info:eu-repo/dai/nl/306644398; Ayres, J.G.; Borm, P.; Brunekreef, B.|info:eu-repo/dai/nl/067548180; Donaldson, K.; Forastiere, F.; Holgate, S.T.; Kreyling, W.; Nemery, B.; Pekkanen, J.; Stone, V.; Wichmann, H.E.; Hoek, G.|info:eu-repo/dai/nl/069553475

    2009-01-01

    ABSTRACT: BACKGROUND: Exposure to fine ambient particulate matter (PM) has consistently been associated with increased morbidity and mortality. The relationship between exposure to ultrafine particles (UFP) and health effects is less firmly established. If UFP cause health effects independently from

  12. Tinnitus referral pathways within the National Health Service in England: a survey of their perceived effectiveness among audiology staff

    Directory of Open Access Journals (Sweden)

    Collins Luke

    2011-07-01

    Full Text Available Abstract Background In the UK, audiology services deliver the majority of tinnitus patient care, but not all patients experience the same level of service. In 2009, the Department of Health released a Good Practice Guide to inform commissioners about key aspects of a quality tinnitus service in order to promote equity of tinnitus patient care in UK primary care, audiology, and in specialist multi-disciplinary centres. The purpose of the present research was to evaluate utilisation and opinions on pathways for the referral of tinnitus patients to and from English Audiology Departments. Methods We surveyed all audiology staff engaged in providing tinnitus services across England. A 36-item questionnaire was mailed to 351 clinicians in all 163 National Health Service (NHS Trusts identified as having a tinnitus service. 138 clinicians responded. The results presented here describe experiences and opinions of the current patient pathways to and from the audiology tinnitus service. Results The most common referral pathway was from general practice to a hospital-based Ear, Nose & Throat department and from there to a hospital-based audiology department (64%. Respondents considered the NHS tinnitus referral process to be generally effective (67%, but expressed needs for improving GP referral and patients' access to services. 'Open access' to the audiology clinic was rarely an option for patients (9%, nor was the opportunity to access specialist counselling provided by clinical psychology (35%. To decrease the number of inappropriate referrals, 40% of respondents called for greater awareness by referrers about the audiology tinnitus service. Conclusions Respondents in the present survey were generally satisfied with the tinnitus referral system. However, they highlighted some potential targets for service improvement including 1] faster and more appropriate referral from GPs, to be achieved through education on tinnitus referral criteria, 2] improved

  13. The effect of public awareness campaigns on suicides: evidence from Nagoya, Japan.

    Science.gov (United States)

    Matsubayashi, Tetsuya; Ueda, Michiko; Sawada, Yasuyuki

    2014-01-01

    Public awareness campaigns about depression and suicide have been viewed as highly effective strategies in preventing suicide, yet their effectiveness has not been established in previous studies. This study evaluates the effectiveness of a public-awareness campaign by comparing suicide counts before and after a city-wide campaign in Nagoya, Japan, where the city government distributed promotional materials that were aimed to stimulate public awareness of depression and promote care-seeking behavior during the period of 2010-2012. In each of the sixteen wards of the city of Nagoya, we count the number of times that the promotional materials were distributed per month and then examine the association between the suicide counts and the frequency of distributions in the months following such distributions. We run a Poisson regression model that controls for the effects of ward-specific observed and unobserved heterogeneities and temporal shocks. Our analysis indicates that more frequent distribution of the campaign material is associated with a decrease in the number of suicides in the subsequent months. The campaign was estimated to have been especially effective for the male residents of the city. The underlying mechanism of how the campaign reduced suicides remains to be unclear. Public awareness campaigns can be an effective strategy in preventing suicide. © 2013 Elsevier B.V. All rights reserved.

  14. Biomarkers of effect in endocrine disruption: how to link a functional assay to an adverse outcome pathway

    Directory of Open Access Journals (Sweden)

    Stefano Lorenzetti

    2015-06-01

    Full Text Available The development of in vitro testing strategies may achieve a cost-effective generation of comprehensive datasets on a large number of chemicals, according to the requirements of the European Regulation REACH. Much emphasis is placed on in vitro methods based on subcellular mechanisms (e.g., nuclear receptor interaction, but it is necessary to define the predictive value of molecular or biochemical changes within an adverse outcome pathway (AOP. AOP pivots on the description of the flow from a molecular initiating event through a cascade of intermediate events needed to produce a specific adverse effect at organism level: downstream responses at cell level are, therefore, essential to define an AOP. Several in vitro assays are based on human cell lines representative of endocrine-targeted tissues (e.g., prostate and on functional biomarkers of clinical relevance (e.g., PSA secretion in human prostate epithelial cells. We discuss the implementation of such functional biomarkers in the AOP context.

  15. Effects of cattle slurry and nitrification inhibitor application on spatial soil O2 dynamics and N2O production pathways

    DEFF Research Database (Denmark)

    Quan, Nguyen Van; Wu, Di; Kong, Xianwang

    2017-01-01

    decomposition. Here, we applied O2 planar optode and N2O isotopomer techniques to investigate the linkage between soil O2 dynamics and N2O production pathways in soils treated with cattle slurry (treatment CS) and tested the effect of the nitrification inhibitor 3,4-dimethyl pyrazole phosphate, DMPP (treatment......Application of cattle slurry to grassland soil has environmental impacts such as ammonia volatilization and greenhouse gas emissions. The extent, however, depends on application method and soil conditions through their effects on infiltration and oxygen (O2) availability during subsequent...... CSD). Twodimensional planar optode images of soil O2 over time revealed that O2 depletion ultimately extended to 1.5 cm depth in CS, as opposed to 1.0 cm in CSD. The 15N site preference (SP) and d18O of emitted N2O varied between 11-25‰and 35e47‰, respectively, indicating a mixture of production...

  16. Cryptotanshinone exhibits therapeutical effects on cerebral stroke through the PI3K/AKT‑eNOS signaling pathway.

    Science.gov (United States)

    Zhu, Weixin; Qiu, Weihong; Lu, Ailan

    2017-12-01

    Cerebral stroke is a kind of acute cerebrovascular disease with high incidence, morbidity and disability. Treatments against various types of cerebral stroke are limited at preventive measurements due to the lack of effective therapeutic method. The present study aimed to investigate the protective effect of cryptotanshinone (CPT) on cerebral stroke, and investigate the possible mechanism involved in order to develop a novel therapy against stoke. The phosphoinositide 3‑kinase membrane translocation of cerebral stroke rats pretreated with CPT at various concentrations were measured, as well as the phosphorylation of protein kinase B (AKT) and endothelial nitric oxide synthase (eNOS). Additionally, the expression level of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and vascular endothelial growth factor were also assessed using western blotting and reverse transcription‑quantitative polymerase chain reaction. Furthermore, biochemical tests were used to measure the activity of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) in both the cerebral cortex and peripheral blood. As a result, CPT‑pretreated rats presented declined phosphoinositide 3‑kinase (PI3K) and AKT expression levels, indicating that the PI3K/AKT signaling pathway was inhibited. Increased Bcl‑2 and NO levels in both the cerebral cortex and peripheral blood demonstrated the anti‑apoptosis and blood vessel protection effect of CPT. Furthermore, increased SOD activity and declined MDA levels demonstrated suppressed lipid peroxidation. In conclusion, CPT exhibited a protective effect against cerebral stroke through inhibition of the PI3K/AKT‑eNOS signaling pathway. These results suggested the potential of CPT as a promising agent in the treatment of cerebral stroke.

  17. How Effective Are Clinical Pathways With and Without Online Peer-Review? An Analysis of Bone Metastases Pathway in a Large, Integrated National Cancer Institute-Designated Comprehensive Cancer Center Network

    Energy Technology Data Exchange (ETDEWEB)

    Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rajagopalan, Malolan S.; Flickinger, John C.; Rakfal, Susan M. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rodgers, Edwin [Via Oncology, Pittsburgh, PA (United States); Heron, Dwight E. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute-Designated Comprehensive Cancer Center Network. Methods: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10-14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. Results: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1-5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1-5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1-1.4) for community and 1.3 (confidence interval, 1.1-1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). Conclusion: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with online clinical

  18. How Effective Are Clinical Pathways With and Without Online Peer-Review? An Analysis of Bone Metastases Pathway in a Large, Integrated National Cancer Institute–Designated Comprehensive Cancer Center Network

    International Nuclear Information System (INIS)

    Beriwal, Sushil; Rajagopalan, Malolan S.; Flickinger, John C.; Rakfal, Susan M.; Rodgers, Edwin; Heron, Dwight E.

    2012-01-01

    Purpose: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute–Designated Comprehensive Cancer Center Network. Methods: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10–14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. Results: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1–5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1–5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1–1.4) for community and 1.3 (confidence interval, 1.1–1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). Conclusion: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with

  19. The Potential Return on Public Investment in Detecting Adverse Drug Effects.

    Science.gov (United States)

    Huybrechts, Krista F; Desai, Rishi J; Park, Moa; Gagne, Joshua J; Najafzadeh, Mehdi; Avorn, Jerry

    2017-06-01

    Many countries lack fully functional pharmacovigilance programs, and public budgets allocated to pharmacovigilance in industrialized countries remain low due to resource constraints and competing priorities. Using 3 case examples, we sought to estimate the public health and economic benefits resulting from public investment in active pharmacovigilance programs to detect adverse drug effects. We assessed 3 examples in which early signals of safety hazards were not adequately recognized, resulting in continued exposure of a large number of patients to these drugs when safer and effective alternative treatments were available. The drug examples studied were rofecoxib, cerivastatin, and troglitazone. Using an individual patient simulation model and the health care system perspective, we estimated the potential costs that could have been averted by early systematic detection of safety hazards through the implementation of active surveillance programs. We found that earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773-$884 million for rofecoxib, $3-$10 million for cerivastatin, and $38-$63 million for troglitazone in the United States through the prevention of adverse events. By contrast, the yearly public investment in Food and Drug Administration initiated population-based pharmacovigilance activities in the United States is about $42.5 million at present. These examples illustrate a critical and economically justifiable role for active adverse effect surveillance in protecting the health of the public.

  20. BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway.

    Science.gov (United States)

    Chen, Mei-Rong; Dai, Ping; Wang, Shu-Fen; Song, Shu-Hua; Wang, Hang-Ping; Zhao, Ya; Wang, Ting-Hua; Liu, Jia

    2016-10-01

    Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.

  1. Protective Effect of Tempol on Acute Kidney Injury Through PI3K/Akt/Nrf2 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Gensheng Zhang

    2016-02-01

    Full Text Available Background/Aims: Tempol is a protective antioxidant against ischemic injury in many animal models. The molecular mechanisms are not well understood. Nuclear factor erythroid 2-related factor (Nrf2 is a master transcription factor during oxidative stress, which is enhanced by activation of protein kinase C (PKC pathway. Another factor, tubular epithelial apoptosis, is mediated by activation of phosphoinositide 3-kinase (PI3K/protein kinase B (PKB, Akt signaling pathway during renal ischemic injury. We tested the hypothesis that tempol activates PKC or PI3K/Akt/Nrf2 pathways to transcribe many genes that coordinate endogenous antioxidant defense. Methods: The right renal pedicle was clamped for 45 minutes and the left kidney was removed to study renal ischemia/reperfusion (I/R injury in C57BL/6 mice. The response was assessed from serum parameters, renal morphology and renal expression of PKC, phosphorylated-PKC (p-PKC, Nrf2, heme oxygenase-1 (HO-1, Akt, phosphorylated-Akt (p-Akt, pro-caspase-3 and cleaved caspase-3 in groups of sham and I/R mice given vehicle, or tempol (50 or 100 mg/kg, intraperitoneal injection. Results: The serum malondialdehyde (MDA, marker of reactive oxygen species doubled and the BUN and creatinine increased 5- to 10-fold after I/R injury. Tempol (50 or 100 mg/kg prevented the increases in MDA but only tempol (50 mg/kg lessened the increases in BUN and creatinine and moderated the acute tubular necrosis. I/R did not change expression of PKC or p-PKC but reduced renal expression of Nrf2, p-Akt, HO-1 and pro-caspase-3 and increased cleaved caspase-3. Tempol (50 mg/kg prevented these changes produced by I/R whereas tempol (100 mg/kg had lesser or inconsistent effects. Conclusion: Tempol (50 mg/kg prevents lipid peroxidation and attenuates renal damage after I/R injury. The beneficial pathway apparently is not dependent on upregulation or phosphorylation of PKC, at lower tempol doses, does implicate upregulation of Akt with

  2. [A comparative study on Koii (public doctor) system and its effect on public health in colonial Taiwan and Korea].

    Science.gov (United States)

    Moon, Myungki

    2014-08-01

    manpower shortage, thus shifting their duties like vaccination onto police officers who was inevitably inferior to doctors in medical terms, whereas vaccination was led by Koiis in Taiwan, with the help of police officers and traditional doctors. The difference between Korea and Taiwan in terms of Koii system and its effect implies that public health network in colonial Taiwan was better organized and more stable than that in colonial Korea, and therefore we should be careful about applying the concept of disciplinary power or modernization theory to colonial medical history of Korea.

  3. Effects of canonical NF-κB signaling pathway on the proliferation and odonto/osteogenic differentiation of human stem cells from apical papilla.

    Science.gov (United States)

    Li, Junjun; Yan, Ming; Wang, Zilu; Jing, Shuanglin; Li, Yao; Liu, Genxia; Yu, Jinhua; Fan, Zhipeng

    2014-01-01

    NF-κB signaling pathway plays a complicated role in the biological functions of mesenchymal stem cells. However, the effects of NF-κB pathway on the odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs) remain unclear. The present study was designed to evaluate the effects of canonical NF-κB pathway on the osteo/odontogenic capacity of SCAPs in vitro. Western blot results demonstrated that NF-κB pathway in SCAPs was successfully activated by TNF-α or blocked by BMS-345541. NF-κB pathway-activated SCAPs presented a higher proliferation activity compared with control groups, as indicated by dimethyl-thiazol-diphenyl tetrazolium bromide assay (MTT) and flow cytometry assay (FCM). Wound scratch assay revealed that NF-κB pathway-activated SCAPs presented an improved migration capacity, enhanced alkaline phosphatase (ALP) activity, and upregulated mineralization capacity of SCAPs, as compared with control groups. Meanwhile, the odonto/osteogenic markers (ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, OPN/OPN, BSP/BSP, DSPP/DSP, and DMP-1/DMP-1) in NF-κB pathway-activated SCAPs were also significantly upregulated as compared with control groups at both protein and mRNA levels. However, NF-κB pathway-inhibited SCAPs exhibited a lower proliferation/migration capacity, and decreased odonto/osteogenic ability in comparison with control groups. Our findings suggest that classical NF-κB pathway plays a paramount role in the proliferation and committed differentiation of SCAPs.

  4. The influence of age-policy changes on the relative age effect across the Australian Rules football talent pathway.

    Science.gov (United States)

    Haycraft, Jade A Z; Kovalchik, Stephanie; Pyne, David B; Larkin, Paul; Robertson, Sam

    2018-03-21

    To identify the influence of age-policy changes on the relative age effect (RAE) across the Australian Football League (AFL) talent pathway. Retrospective cross-sectional analysis of junior AFL players attending the National Draft (National), State, and State Under 16s (U16) combines between 1999-2016. Birth-date data was obtained for players attending the AFL State U16 (n=663, age: 15.9±0.4years), State (n=803, age: 19.1±1.7years), National (n=1111, age: 18.3±0.8years) combines. Corresponding aged-matched Australian general population birth rate data was also collected. A chi-squared analysis comparing birth month distributions found all combine groups differed significantly from the general population (Under 16s: χ 2 =62.61, State: χ 2 =38.83, National: χ 2 =129.13, pborn in January (4.9%, ptalent pathways. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  5. Effects of chronic REM sleep restriction on D1 receptor and related signal pathways in rat prefrontal cortex.

    Science.gov (United States)

    Han, Yan; Wen, Xiaosa; Rong, Fei; Chen, Xinmin; Ouyang, Ruying; Wu, Shuai; Nian, Hua; Ma, Wenling

    2015-01-01

    The prefrontal cortex (PFC) mediates cognitive function that is sensitive to disruption by sleep loss, and molecular mechanisms regulating neural dysfunction induced by chronic sleep restriction (CSR), particularly in the PFC, have yet to be completely understood. The aim of the present study was to investigate the effect of chronic REM sleep restriction (REM-CSR) on the D1 receptor (D1R) and key molecules in D1R' signal pathways in PFC. We employed the modified multiple platform method to create the REM-CSR rat model. The ultrastructure of PFC was observed by electron microscopy. HPLC was performed to measure the DA level in PFC. The expressions of genes and proteins of related molecules were assayed by real-time PCR and Western blot, respectively. The general state and morphology of PFC in rats were changed by CSR, and DA level and the expression of D1R in PFC were markedly decreased (P CSR rats (P CSR induced cognitive dysfunction, and the PKA pathway of D1R may play an important role in the impairment of advanced neural function.

  6. Signaling pathways underpinning the manifestations of ionizing radiation-induced bystander effects.

    Science.gov (United States)

    Hamada, Nobuyuki; Maeda, Munetoshi; Otsuka, Kensuke; Tomita, Masanori

    2011-06-01

    For nearly a century, ionizing radiation has been indispensable to medical diagnosis. Furthermore, various types of electromagnetic and particulate radiation have also been used in cancer therapy. However, the biological mechanism of radiation action remains incompletely understood. In this regard, a rapidly growing body of experimental evidence indicates that radiation exposure induces biological effects in cells whose nucleus has not been irradiated. This phenomenon termed the 'non-targeted effects' challenges the long-held tenet that radiation traversal through the cell nucleus is a prerequisite to elicit genetic damage and biological responses. The non-targeted effects include biological effects in cytoplasm-irradiated cells, bystander effects that arise in non-irradiated cells having received signals from irradiated cells, and genomic instability occurring in the progeny of irradiated cells. Such non-targeted responses are interrelated, and the bystander effect is further related with an adaptive response that manifests itself as the attenuated stressful biological effects of acute high-dose irradiation in cells that have been pre-exposed to low-dose or low-dose-rate radiation. This paper reviews the current body of knowledge about the bystander effect with emphasis on experimental approaches, in vitro and in vivo manifestations, radiation quality dependence, temporal and spatial dependence, proposed mechanisms, and clinical implications. Relations of bystander responses with the effects in cytoplasm-irradiated cells, genomic instability and adaptive response will also be briefly discussed.

  7. Stigma, discrimination, treatment effectiveness, and policy: public views about drug addiction and mental illness.

    Science.gov (United States)

    Barry, Colleen L; McGinty, Emma E; Pescosolido, Bernice A; Goldman, Howard H

    2014-10-01

    Public attitudes about drug addiction and mental illness were compared. A Web-based national survey (N=709) was conducted to compare attitudes about stigma, discrimination, treatment effectiveness, and policy support in regard to drug addiction and mental illness. Respondents held significantly more negative views toward persons with drug addiction. More respondents were unwilling to have a person with drug addiction marry into their family or work closely with them. Respondents were more willing to accept discriminatory practices against persons with drug addiction, more skeptical about the effectiveness of treatments, and more likely to oppose policies aimed at helping them. Drug addiction is often treated as a subcategory of mental illness, and insurance plans group them together under the rubric of "behavioral health." Given starkly different public views about drug addiction and mental illness, advocates may need to adopt differing approaches to reducing stigma and advancing public policy.

  8. Fukushima effects in Germany? Changes in media coverage and public opinion on nuclear power.

    Science.gov (United States)

    Arlt, Dorothee; Wolling, Jens

    2016-10-01

    Based on a literature review on factors that explain media effects and previous findings on media coverage and public opinion on nuclear power, this article examines the effects of Fukushima on media coverage and public opinion in Germany in two studies. The first study uses content analysis data to analyse changes in media coverage, and the second one is based on panel survey data to examine attitude changes on an individual level. The results of both studies show changes in media coverage and public opinion on nuclear power. Furthermore, the second study reveals that individual attitude changes cannot necessarily be explained by the same factors as the distribution of attitudes. © The Author(s) 2015.

  9. Between the effectivity and affectivity: new teachers in times of new public management

    Directory of Open Access Journals (Sweden)

    Rodrigo Andres Soto Lagos

    2016-11-01

    Full Text Available The Educational Public Policy in the current neoliberal context hold their proposals under the New Public Management (NPM. These devices promote a professionalization of the teaching role, positioning them as responsible for changes in education in the country. This research focuses on the discourse analysis of twelve official documents of the Ministry of Education of Chile, which under the logic of NPM promote emotions and effectiveness to interpellate teachers and invite them to work in adverse conditions. The results shows two interpellations to teachers in the country, one that relates to the effectiveness, based on competition, and other centered in affections, both challenging teachers individually and emotional. It is discussed relative to the direction of public policy devices that are supported from the NPM.

  10. Agorá Acoustics - Effects of arcades on the acoustics of public squares

    DEFF Research Database (Denmark)

    Paini, Dario; Gade, Anders Christian; Rindel, Jens Holger

    2005-01-01

    This paper is part of a PhD work, dealing with the acoustics of the public squares (‘Agorá Acoustics’), especially when music (amplified or not) is played. Consequently, our approach will be to evaluate public squares using the same set of acoustics concepts for subjective evaluation and objective...... measurements as applied for concert halls and theatres. In this paper the acoustical effects of arcades will be studied, in terms of reverberation (EDT and T30), clarity (C80), intelligibility (STI) and other acoustical parameters. For this purpose, also the theory of coupled rooms is applied and compared...... with results. An acoustic modelling program, ODEON 7.0, was used for this investigation. Three different sizes of public squares were considered. In order to evaluate the ‘real’ effects of the arcades on the open square, models of all three squares were designed both with and without arcades. The sound source...

  11. Differential effects of negative publicity on beef consumption according to household characteristics in South Korea.

    Science.gov (United States)

    Youn, Hyungho; Lim, Byung In; Jin, Hyun Joung

    2012-07-01

    This paper examines how South Korean households responded to an unprecedented boycott campaign against US beef from spring to summer of 2008, and investigates differential responses in relation to households' characteristics. It was found that beef consumption reduced by 4.8% immediately after the so-called candle-light demonstration. Instead, pork and chicken consumption increased by 17.2% and 16.6%, respectively. This confirms a substitution effect due to the negative publicity concerning US beef. It was also found that the negative publicity effect was transitory and the reactions of consumers were not uniform; they differed depending on their socio-economic characteristics. The econometric model revealed that younger, less-educated, and/or lower-income households were more susceptible to the negative publicity, and reduced their beef consumption more than other households. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Technological Innovation and Beyond: Exploring Public Value of University Inventions Based on Contingent Effectiveness Model

    DEFF Research Database (Denmark)

    Milana, Evita; Li-Ying, Jason; Faria, Lourenco

    2017-01-01

    University inventions are traditionally seen as significant input into development of new technologies and innovations in the market as they generate growth and regional development. (REF) Yet, these inventions developed into new technologies can simultaneously create public values such as those...... that are related with sustainability goals. In this paper, we apply the Contingent Effectiveness Model by Bozeman et.al. (2015) as a framework to consider the effectiveness of technology transfer from university to industry via licensing, and examine what values derive during the commercialization process...... of university inventions. We define four main values: technological, economic, social and environmental, and place the latter two under the concept of public value. The aim of this paper is to expand the understanding of public value and incorporate it into technology transfer literature. We assign...

  13. Pathways to Improved Development for Children Living in Poverty: A Randomized Effectiveness Trial in Rural Mexico

    Science.gov (United States)

    Knauer, Heather A.; Kagawa, Rose M. C.; García-Guerra, Armando; Schnaas, Lourdes; Neufeld, Lynnette M.; Fernald, Lia C. H.

    2016-01-01

    Conditional cash transfer programs (CCTs) have shown mixed effects on child development outcomes in the context of poverty. Direct parenting support integrated with CCTs may improve the effectiveness of CCTs for children's development, and benefits could occur via improvements in parenting practices or the home environment. Here, we use data from…

  14. Lobbying and Social Participation – Key Features for an Effective Public Administration in Romania

    Directory of Open Access Journals (Sweden)

    Laura Maria IRIMIEȘ

    2017-12-01

    Full Text Available Lobbying is one of the main structural elements of democratic governance and sustainable development and is essential to achieving competitive and effi cient administrative and decisional processes in local governance. Successfully implementing lobbying regulations and techniques is of extreme importance for any public system, where social participation in the decision-making process can strongly contribute to social, political and economic / fi nancial effi - ciency. Over the last 15 years, several legislative initiatives have tried to design a coherent framework for lobby, but they are still unapplied either due to insuffi cient public understanding of the concept, or due to more or less justifi ed uncertainties and fears. The necessity of regulating lobbying in Romania is placed in a context where an important number of anticorruption international and domestic recommendations and state reliability statistics, added to a certain lack of effectiveness in time and public money management, show that the public administration system needs to be reformed. And lobbying is, as the following article shows, a must for any public reform of public administration in Romania. The case of multilingual entrance signs / labels in Cluj-Napoca is an unquestionable and unbeatable example that the simple existence of legal frameworks of lobbying could turn into real time, energy and money savers.

  15. Radioactive wastes repository in Temascalapa, State of Mexico, public opinion. Determination of health effects

    International Nuclear Information System (INIS)

    Solis Tinoco, E.

    1998-01-01

    Nuclear waste usually concerns public about the impact on public health and the environment. In Mexico, such interest exists, particularly in the Temascalapa Municipality, Mexico where a low level waste repository recognized by the IAEA, has been functioning since 1972. Maquixco repository is located at 42 Kilometers northeast of Mexico City. Although the environmental radiological monitoring records have demonstrated negligible impact on the environment, in 1998 an unusual public polemic on radioactive health effects appeared among Temascalapa residents. This paper presents a research performed during 1998 with the participation of the National Nuclear Research Institute of Mexico and the National Autonomous University of Mexico. The research design allowed the involvement of local authorities, as a way of stimulate public participation. The research was performed in nine locations of the Temascalapa Municipality, it was focused on public polemics, associated to Maquixco repository as well as trying to identify demographic factors that exert influence on public attitudes. There are also presented the results of personal dosimetry analysis performed on a four hundred residents sample of this Municipality. (Author)

  16. Characteristics and Pathways of Long-Stay Patients in High and Medium Secure Settings in England; A Secondary Publication From a Large Mixed-Methods Study

    Directory of Open Access Journals (Sweden)

    Birgit A. Völlm

    2018-04-01

    Full Text Available Background: Many patients experience extended stays within forensic care, but the characteristics of long-stay patients are poorly understood.Aims: To describe the characteristics of long-stay patients in high and medium secure settings in England.Method: Detailed file reviews provided clinical, offending and risk data for a large representative sample of 401 forensic patients from 2 of the 3 high secure settings and from 23 of the 57 medium secure settings in England on 1 April 2013. The threshold for long-stay status was defined as 5 years in medium secure care or 10 years in high secure care, or 15 years in a combination of high and medium secure settings.Results: 22% of patients in high security and 18% in medium security met the definition for “long-stay,” with 20% staying longer than 20 years. Of the long-stay sample, 58% were violent offenders (22% both sexual and violent, 27% had been convicted for violent or sexual offences whilst in an institutional setting, and 26% had committed a serious assault on staff in the last 5 years. The most prevalent diagnosis was schizophrenia (60% followed by personality disorder (47%, predominantly antisocial and borderline types; 16% were categorised as having an intellectual disability. Overall, 7% of the long-stay sample had never been convicted of any offence, and 16.5% had no index offence prompting admission. Although some significant differences were found between the high and medium secure samples, there were more similarities than contrasts between these two levels of security. The treatment pathways of these long-stay patients involved multiple moves between settings. An unsuccessful referral to a setting of lower security was recorded over the last 5 years for 33% of the sample.Conclusions: Long-stay patients accounted for one fifth of the forensic inpatient population in England in this representative sample. A significant proportion of this group remain unsettled. High levels of

  17. Effects of a traditional Chinese medicine, Longdanxiegan formula granule, on Toll-like receptor pathway in female guinea pigs with recurrent genital herpes.

    Science.gov (United States)

    Kuang, Lin; Deng, Yihui; Liu, Xiaodan; Zou, Zhixiang; Mi, Lan

    2016-04-01

    The aim of the present study was to investigate the effects of Longdanxiegan formula granule (LDXGFG), a Chinese traditional medicine on Toll-like receptor (TLR) pathway in recurrent genital herpes. An experimental recurrent genital herpes model was constructed using herpes guinea pig model. The effect of LDXGFG on expression levels of TLR pathway genes were detected using real-time polymerase chain reaction. Furthermore, the dendritic cells and Langerhans cells were isolated and the TLR pathway genes of these cells were assayed after LDXGFG treatment. The result suggested two different expression patterns of TLR pathway genes in genital herpes and recurrent genital herpes, including upregulated genes and downregulated genes. TLR1, TLR4, TLR6, TLR7, TLR8, TLR9, and TLR10 showed a significant decrease while, TLR2, TLR3, and TLR5 increased in genital herpes and recurrent genital herpes guinea pigs. Meanwhile, the downregulated genes in genital herpes and recurrent genital herpes were stimulated by LDXGFG. By contrast, the upregulated genes decreased significantly after LDXGFG treatment. In both dendritic cells and Langerhans cells, the TLR pathway genes exhibited same pattern: the LDXGFG corrected the abnormal expression of TLR pathway genes. The present results suggest that LDXGFG is an alternative, inexpensive, and lasting-effect medicine for herpes simplex virus 2 infection. Copyright © 2016. Published by Elsevier B.V.

  18. Sediment pathways in a tropical forest: effects of logging roads and skid trails

    Science.gov (United States)

    Sidle, Roy C.; Sasaki, Shozo; Otsuki, Mieko; Noguchi, Shoji; Rahim Nik, Abdul

    2004-03-01

    Significant erosion occurred from recently constructed forest logging roads and skid trails in a small headwater catchment in Peninsular Malaysia. Soil loss was estimated by measuring dimensions of all significant rills and gullies along the road, as well as by measuring height of preserved soil pedestals in sidecast and fill material and on skid trails. Estimates of surface erosion from logging roads and skid trails were 272 +/- 20 t ha-1 year-1 and 275 +/- 20 t ha-1 year-1 respectively. However, owing to lack of connectivity of skid trails to the stream, much of the sediment mobilized on skid trails was stored either on adjacent hillslopes or the trails themselves, rather than being transported to the stream system, as was the case for the road. Steeper skid trails (>20% gradient) had slightly higher erosion rates (320 +/- 24 t ha-1 year-1) than trails with gentler gradients (245-264 t ha-1 year-1). Some 60% of the soil loss on logging roads comes from erosion of the running surface. Disturbed cut and fill material along the road supplied the remaining 40% of the soil loss from roads. Roads and skid trails had no designed drainage systems; runoff discharged onto the hillslope at 25 major discharge nodes from the logging road (690 m total length) and at 34 nodes from skid trails (2300 m). Sediment pathways were either fully or moderately connected to headwater channels at 64% of the logging road nodes, but at only 26% of the nodes emanating from skid trails. A detailed sediment budget revealed that 78% of the soil loss from the road system (including log landings) was delivered to the stream in the first 16 months after logging began. Most (90%) of the deposition from skid trails occurred below just three discharge nodes. Runoff from and onto skid trails often exacerbated the sediment connectivity to channels. Clearly, sediment discharge from logging roads was more highly connected to the stream than discharge from skid trails. Once in the channel, much of this

  19. Mechanisms underlying the perifocal neuroprotective effect of the Nrf2–ARE signaling pathway after intracranial hemorrhage

    Directory of Open Access Journals (Sweden)

    Yin XP

    2015-11-01

    Full Text Available Xiao-ping Yin,1,2 Zhi-ying Chen,2 Jun Zhou,1 Dan Wu,1,3 Bing Bao2 1Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, People’s Republic of China; 3Department of Neurology, The Sixth Hospital of Wuhan, Wuhan, People’s Republic of China Background: It has been found that nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2–ARE signaling pathway plays a role in antioxidative response, anti-inflammatory response, and neuron-protection in intracerebral hemorrhage (ICH. The aim of this study is to explore mechanisms underlying the perifocal neuroprotective effect of the Nrf2–ARE signaling pathway after ICH.Methods: There were a total of 90 rats with basal ganglia hemorrhage, which were randomly divided into the following four groups: ICH (Sprague–Dawley rats with autologous femoral arterial blood injection into the basal ganglia, sulforaphane (SFN (SFN was intraperitoneally administered into rats, retinoic acid (RA (RA was intraperitoneally administered into rats, and dimethyl sulfoxide (the rats were treated with dimethyl sulfoxide. We observed the neurological score of the rats in the different groups, and collected brain tissues for immunofluorescence, Western blot, and reverse transcription polymerase chain reaction to detect expression of Nrf2, heme oxygenase (HO-1, nuclear factor-κB (NF-κB, and tumor necrosis factor-α (TNF-α.Results: The results indicated that neurological dysfunction of rats was significantly improved in the SFN group, and the expressions of Nrf2 and HO-1 in tissues surrounding the hemorrhage were increased. Also, the level of NF-κB and TNF-α were reduced compared to the ICH group. The RA group exhibited more severe neurological dysfunction and lower levels of Nrf2 and HO-1 than the SFN and ICH groups. Compared to the ICH group, the NF

  20. Correcting for day of the week and public holiday effects: improving a national daily syndromic surveillance service for detecting public health threats.

    Science.gov (United States)

    Buckingham-Jeffery, Elizabeth; Morbey, Roger; House, Thomas; Elliot, Alex J; Harcourt, Sally; Smith, Gillian E

    2017-05-19

    As service provision and patient behaviour varies by day, healthcare data used for public health surveillance can exhibit large day of the week effects. These regular effects are further complicated by the impact of public holidays. Real-time syndromic surveillance requires the daily analysis of a range of healthcare data sources, including family doctor consultations (called general practitioners, or GPs, in the UK). Failure to adjust for such reporting biases during analysis of syndromic GP surveillance data could lead to misinterpretations including false alarms or delays in the detection of outbreaks. The simplest smoothing method to remove a day of the week effect from daily time series data is a 7-day moving average. Public Health England developed the working day moving average in an attempt also to remove public holiday effects from daily GP data. However, neither of these methods adequately account for the combination of day of the week and public holiday effects. The extended working day moving average was developed. This is a further data-driven method for adding a smooth trend curve to a time series graph of daily healthcare data, that aims to take both public holiday and day of the week effects into account. It is based on the assumption that the number of people seeking healthcare services is a combination of illness levels/severity and the ability or desire of patients to seek healthcare each day. The extended working day moving average was compared to the seven-day and working day moving averages through application to data from two syndromic indicators from the GP in-hours syndromic surveillance system managed by Public Health England. The extended working day moving average successfully smoothed the syndromic healthcare data by taking into account the combined day of the week and public holiday effects. In comparison, the seven-day and working day moving averages were unable to account for all these effects, which led to misleading smoothing

  1. Correcting for day of the week and public holiday effects: improving a national daily syndromic surveillance service for detecting public health threats

    Directory of Open Access Journals (Sweden)

    Elizabeth Buckingham-Jeffery

    2017-05-01

    Full Text Available Abstract Background As service provision and patient behaviour varies by day, healthcare data used for public health surveillance can exhibit large day of the week effects. These regular effects are further complicated by the impact of public holidays. Real-time syndromic surveillance requires the daily analysis of a range of healthcare data sources, including family doctor consultations (called general practitioners, or GPs, in the UK. Failure to adjust for such reporting biases during analysis of syndromic GP surveillance data could lead to misinterpretations including false alarms or delays in the detection of outbreaks. The simplest smoothing method to remove a day of the week effect from daily time series data is a 7-day moving average. Public Health England developed the working day moving average in an attempt also to remove public holiday effects from daily GP data. However, neither of these methods adequately account for the combination of day of the week and public holiday effects. Methods The extended working day moving average was developed. This is a further data-driven method for adding a smooth trend curve to a time series graph of daily healthcare data, that aims to take both public holiday and day of the week effects into account. It is based on the assumption that the number of people seeking healthcare services is a combination of illness levels/severity and the ability or desire of patients to seek healthcare each day. The extended working day moving average was compared to the seven-day and working day moving averages through application to data from two syndromic indicators from the GP in-hours syndromic surveillance system managed by Public Health England. Results The extended working day moving average successfully smoothed the syndromic healthcare data by taking into account the combined day of the week and public holiday effects. In comparison, the seven-day and working day moving averages were unable to account for all

  2. The use of performance measurement systems in the public sector: effects on performance

    NARCIS (Netherlands)

    Speklé, R.; Verbeeten, F.H.M.

    2014-01-01

    We study the use of performance measurement systems in the public sector. We hypothesize that the way in which these systems are being used affects organizational performance, and that these performance effects depend on contractibility. Contractibility encompasses clarity of goals, the ability to

  3. The Student Equity Effects of the Public School Finance System in Louisiana.

    Science.gov (United States)

    Geske, Terry G.; LaCost, Barbara Y.

    1990-01-01

    Investigates the student equity effects of Louisiana's public school finance program in terms of fiscal neutrality and revenue inequality over a nine-year period, using regression techniques. Overall, Louisiana's system became less equal over the time period examined, while revenue distribution became more equal. Includes 35 references. (MLH)

  4. The Effect of Pecha Kucha Presentations on Students' English Public Speaking Anxiety

    Science.gov (United States)

    Coskun, Abdullah

    2017-01-01

    The objective of this study is to investigate the effect of the Pecha Kucha presentation format on English as foreign language learners' public speaking anxiety. The participants were 49 students in the English Translation and Interpretation Department of a state university in Turkey. A pre- and post-test experimental research design was used in…

  5. Evaluating the Effect of a Television Public Service Announcement about Epilepsy

    Science.gov (United States)

    Martiniuk, Alexandra L. C.; Secco, Mary; Yake, Laura; Speechley, Kathy N.

    2010-01-01

    Public service announcements (PSAs) are non-commercial advertisements aiming to improve knowledge, attitudes and/or behavior. No evaluations of epilepsy PSAs exist. This study sought to evaluate a televised PSA showing first aid for a seizure. A multilevel regression analysis was used to determine the effect of the PSA on epilepsy knowledge and…

  6. Mass Media and Global Warming: A Public Arenas Model of the Greenhouse Effect's Scientific Roots.

    Science.gov (United States)

    Neuzil, Mark

    1995-01-01

    Uses the Public Arenas model to examine the historical roots of the greenhouse effect issue as communicated in scientific literature from the early 1800s to modern times. Utilizes a constructivist approach to discuss several possible explanations for the rise and fall of global warming as a social problem in the scientific arena. (PA)

  7. School Violence and Its Effect on the Constitutionality of Public School Uniform Policies.

    Science.gov (United States)

    Starr, Jennifer

    2000-01-01

    The Arizona Court of Appeals, in the first court decision regarding public school uniform policies, held that mandatory school uniforms do not violate students' First Amendment rights. Discusses the Arizona decision and its effect on the structuring of school uniform policies and their potential successful institution at the high school level. (31…

  8. The Moderating Effect of Sex on the Prediction of Job Satisfaction in the Public Sector.

    Science.gov (United States)

    Lee, Raymond

    1982-01-01

    Examined the moderating effect of sex on the contribution of specific job characteristics as sources of general job satisfaction. A survey of over 2,000 public employees showed only minimal sex differences. Supervision was more important to females. Females also tended to be more satisfied with their salaries. (JAC)

  9. Assessing the Warm Glow Effect in Contingent Valuations for Public Libraries

    Science.gov (United States)

    Lee, Soon-Jae; Chung, Hye-Kyung; Jung, Eun-Joo

    2010-01-01

    This article aims to present evidence of the warm glow effect in a public library setting. More specifically, it tests whether individual respondents with different values for the warm glow component report different values for their willingness to pay (WTP). The data come from a contingent valuation survey conducted on randomly selected citizens…

  10. School Choice in Indianapolis: Effects of Charter, Magnet, Private, and Traditional Public Schools

    Science.gov (United States)

    Berends, Mark; Waddington, R. Joseph

    2018-01-01

    School choice researchers are often limited to comparing one type of choice with another (e.g., charter schools vs. traditional public schools). One area researchers have not examined is the effects of different school types within the same urban region. We fill this gap by analyzing longitudinal data for students (grades 3-8) in Indianapolis,…

  11. Administrative Support and Its Mediating Effect on US Public School Teachers

    Science.gov (United States)

    Tickle, Benjamin R.; Chang, Mido; Kim, Sunha

    2011-01-01

    This study examined the effect of administrative support on teachers' job satisfaction and intent to stay in teaching. The study employed a path analysis to the data of regular, full-time, public school teachers from the Schools and Staffing Survey teacher questionnaire. Administrative support was the most significant predictor of teachers' job…

  12. The Social Effects of Advertising as Perceived by Advertising Executives, Businessmen, and the General Public.

    Science.gov (United States)

    Surlin, Stuart H.

    This study attempts to compare the perceptions and self-reported behavior of high, middle, and low authoritarian advertising executives, business executives, and members of the general public concerning the social effects of advertising. For the advertising sample, a total of 393 men and women were selected according to their executive positions…

  13. Evaluation of the effective dose equivalent to tbe public of Pavia after the Chernobyl nuclear accident

    International Nuclear Information System (INIS)

    Altieri, S.; Berzero, A.; Meloni, S.; Rosti, G.; Genova, N.

    1988-01-01

    The Chernobyl radionuclide monitoring campaign in air particulate and foodstuffs was carried out and continued up to June 1987. On the basis of collected data estimates of the collective effective dose equivalent commitment to the public of province of Pavia, by external irradiation or by inhalation, were carried out and are reported in the present paper

  14. Effects of Competing Narratives on Public Perceptions of Opioid Pain Reliever Addiction during Pregnancy.

    Science.gov (United States)

    Kennedy-Hendricks, Alene; McGinty, Emma E; Barry, Colleen L

    2016-10-01

    Opioid pain reliever addiction has increased among women of reproductive age over the last fifteen years. News media and public attention have focused on the implications of this trend for infants exposed to opioids prenatally, with state policy responses varying in the extent to which they are punitive or public health oriented. We fielded a six-group randomized experiment among a nationally representative sample of US adults to test the effects of narratives portraying a woman with opioid pain reliever addiction during pregnancy on beliefs about people addicted to opioid pain relievers, perceptions of treatment effectiveness, policy attitudes, and emotional responses. Portraying a high socioeconomic status (SES) woman in the narrative lowered perceptions of individual blame for addiction and reduced public support for punitive policies. Depicting the barriers to treatment faced by a low SES woman lowered support for punitive policies and increased support for expanded insurance coverage for treatment. The extent to which narratives portraying successfully treated addiction affected public attitudes depended on the SES of the woman portrayed. These findings can inform the development of communication strategies to reduce stigma toward this population, reduce support for punitive policies, and increase support for more public health-oriented approaches to addressing this problem. Copyright © 2016 by Duke University Press.

  15. Stigma, Discrimination, Treatment Effectiveness and Policy Support: Comparing Public Views about Drug Addiction with Mental Illness

    Science.gov (United States)

    Barry, Colleen L; McGinty, Emma Elizabeth; Pescosolido, Bernice; Goldman, Howard H.

    2014-01-01

    Objective This study compares current public attitudes about drug addiction with attitudes about mental illness. Methods A web-based national public opinion survey (N=709) was conducted to compare attitudes about stigma, discrimination, treatment effectiveness, and policy support. Results Respondents hold significantly more negative views toward persons with drug addiction compared to those with mental illness. More respondents were unwilling to have a person with drug addiction marry into their family or work closely with them on a job. Respondents were more willing to accept discriminatory practices, more skeptical about the effectiveness of available treatments, and more likely to oppose public policies aimed at helping persons with drug addiction. Conclusions Drug addiction is often treated as a sub-category of mental illness, and health insurance benefits group these conditions together under the rubric of behavioral health. Given starkly different public views about drug addiction and mental illness, advocates may need to adopt differing approaches for advancing stigma reduction and public policy. PMID:25270497

  16. Blended learning is an effective strategy for acquiring competence in public health biostatistics.

    Science.gov (United States)

    Milic, Natasa; Masic, Srdjan; Bjegovic-Mikanovic, Vesna; Trajkovic, Goran; Marinkovic, Jelena; Milin-Lazovic, Jelena; Bukumiric, Zoran; Savic, Marko; Cirkovic, Andja; Gajic, Milan; Stanisavljevic, Dejana

    2018-04-01

    We sought to determine whether blended learning is an effective strategy for acquiring competence in public health biostatistics. The trial was conducted with 69 Masters' students of public health attending the School of Public Health at University of Belgrade. Students were exposed to the traditional and blended learning styles. Blended learning included a combination of face-to-face and distance learning methodologies integrated into a single course. Curriculum development was guided by competencies as suggested by the Association of Schools of Public Health in the European Region (ASPHER). Teaching methods were compared according to the final competence score. Forty-four students were enrolled in the traditional method of education delivery, and 25 to the blended learning format. Mean exam scores for the blended learning group were higher than for the on-site group for both the final statistics score (89.65 ± 6.93 vs. 78.21 ± 13.26; p  0.8). A blended learning approach is an attractive and effective way of acquiring biostatistics competence for Masters of Public Health (MPH) graduate students.

  17. Testing a hierarchy-of-effects model: pathways from awareness to outcomes in the VERB campaign 2002-2003.

    Science.gov (United States)

    Bauman, Adrian; Bowles, Heather R; Huhman, Marian; Heitzler, Carrie D; Owen, Neville; Smith, Ben J; Reger-Nash, Bill

    2008-06-01

    The McGuire hierarchy-of-effects (HOE) model, used extensively in mass-media interventions to describe the mechanisms for understanding effects, has not been tested in physical activity campaigns. Data collected at baseline (2002) and follow-up (2003) surveys in the VERB evaluation were used in structural equation modeling to test pathways and hierarchies of campaign effects. Population-based cohort of youth aged 9-13 years (N=2364) for whom complete baseline and follow-up data were available. Awareness of the VERB campaign, understanding of the VERB message, attitude toward being active, outcome expectations, and physical activity participation. Among youth aged 9-13 years (tweens) in the study cohort, significant paths were identified between awareness and understanding (0.72, pmodel and suggest that increased awareness and understanding were the key proximal effects that led to behavior change. A distinct sequence of effects, which bypassed attitudes and outcome expectations, was found for these U.S. young people. The findings could inform the design of future campaigns to address youth physical activity.

  18. The effect of selected metals on the central metabolic pathways in ...

    African Journals Online (AJOL)

    2006-10-04

    Oct 4, 2006 ... University of Pretoria, PO Box 2034, Pretoria, 0001, South Africa ... use these natural resources as food and water supplies and are therefore also exposed to .... adverse health effects on humans and indigenous biota (Ohe et.

  19. [Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder].

    Science.gov (United States)

    Zhou, Rong-Yi; Wang, Jiao-Jiao; You, Yue; Sun, Ji-Chao; Song, Yu-Chen; Yuan, Hai-Xia; Han, Xin-Min

    2017-05-01

    To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD). A total of 40 SHR rats were randomly divided into five groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA. Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (PATPase activity (PATPase activity (PATPase activity (PATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.

  20. Learning Effective Treatment Pathways for Type-2 Diabetes from a clinical data warehouse.

    Science.gov (United States)

    Vashisht, Rohit; Jung, Ken; Shah, Nigam

    2016-01-01

    Treatment guidelines for management of type-2 diabetes mellitus (T2DM) are controversial because existing evidence from randomized clinical trials do not address many important clinical questions. Data from Electronic Medical Records (EMRs) has been used to profile first line therapy choices, but this work did not elucidate the factors underlying deviations from current treatment guidelines and the relative efficacy of different treatment options. We have used data from the Stanford Hospital to attempt to address these issues. Clinical features associated with the initial choice of treatment were effectively re-discovered using a machine learning approach. In addition, the efficacies of first and second line treatments were evaluated using Cox proportional hazard models for control of Hemoglobin A 1c . Factors such as acute kidney disorder and liver disorder were predictive of first line therapy choices. Sitagliptin was the most effective second-line therapy, and as effective as metformin as a first line therapy.

  1. Assessment of the effect of visual impairment on mortality through multiple health pathways: structural equation modeling.

    Science.gov (United States)

    Christ, Sharon L; Lee, David J; Lam, Byron L; Zheng, D Diane; Arheart, Kristopher L

    2008-08-01

    To estimate the direct effects of self-reported visual impairment (VI) on health, disability, and mortality and to estimate the indirect effects of VI on mortality through health and disability mediators. The National Health Interview Survey (NHIS) is a population-based annual survey designed to be representative of the U.S. civilian noninstitutionalized population. The National Death Index of 135,581 NHIS adult participants, 18 years of age and older, from 1986 to 1996 provided the mortality linkage through 2002. A generalized linear structural equation model (GSEM) with latent variable was used to estimate the results of a system of equations with various outcomes. Standard errors and test statistics were corrected for weighting, clustering, and stratification. VI affects mortality, when direct adjustment was made for the covariates. Severe VI increases the hazard rate by a factor of 1.28 (95% CI: 1.07-1.53) compared with no VI, and some VI increases the hazard by a factor of 1.13 (95% CI: 1.07-1.20). VI also affects mortality indirectly through self-rated health and disability. The total effects (direct effects plus mediated effects) on the hazard of mortality of severe VI and some VI relative to no VI are hazard ratio (HR) 1.54 (95% CI: 1.28-1.86) and HR 1.23 (95% CI: 1.16-1.31), respectively. In addition to the direct link between VI and mortality, the effects of VI on general health and disability contribute to an increased risk of death. Ignoring the latter may lead to an underestimation of the substantive impact of VI on mortality.

  2. Agmatine enhances the antidepressant-like effect of lithium in mouse forced swimming test through NMDA pathway.

    Science.gov (United States)

    Mohseni, Gholmreza; Ostadhadi, Sattar; Imran-Khan, Muhammad; Norouzi-Javidan, Abbas; Zolfaghari, Samira; Haddadi, Nazgol-Sadat; Dehpour, Ahmad-Reza

    2017-04-01

    Depression is one the world leading global burdens leading to various comorbidities. Lithium as a mainstay in the treatment of depression is still considered gold standard treatment. Similar to lithium another agent agmatine has also central protective role against depression. Since, both agmatine and lithium modulate various effects through interaction with NMDA receptor, therefore, in current study we aimed to investigate the synergistic antidepressant-like effect of agmatine with lithium in mouse force swimming test. Also to know whether if such effect is due to interaction with NMDA receptor. In our present study we found that when potent dose of lithium (30mg/kg) was administered, it significantly decreased the immobility time. Also, when subeffective dose of agmatine (0.01mg/kg) was coadministered with subeffective dose of lithium (3mg/kg), it potentiated the antidepressant-like effect of subeffective dose of lithium. For the involvement of NMDA receptor in such effect, we administered NMDA receptor antagonist MK-801 (0.05mg/kg) with a combination of subeffective dose of lithium (3mg/kg) and agmatine (0.001mg/kg). A significant antidepressant-like effect was observed. Furthermore, when subeffective dose (50 and 75mg/kg) of NMDA was given it inhibited the synergistic effect of agmatine (0.01mg/kg) with lithium (3mg/kg). Hence, our finding demonstrate that agmatine have synergistic effect with lithium which is mediated by NMDA receptor pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Libidibia ferrea mature seeds promote antinociceptive effect by peripheral and central pathway: possible involvement of opioid and cholinergic receptors.

    Science.gov (United States)

    Sawada, Luis Armando; Monteiro, Vanessa Sâmia da Conçeição; Rabelo, Guilherme Rodrigues; Dias, Germana Bueno; Da Cunha, Maura; do Nascimento, José Luiz Martins; Bastos, Gilmara de Nazareth Tavares

    2014-01-01

    Libidibia ferrea (LF) is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF), partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg), naloxone (5 mg/kg) in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies.

  4. Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors

    Directory of Open Access Journals (Sweden)

    Luis Armando Sawada

    2014-01-01

    Full Text Available Libidibia ferrea (LF is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF, partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg, naloxone (5 mg/kg in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies.

  5. Opposing effects of bile acids deoxycholic acid and ursodeoxycholic acid on signal transduction pathways in oesophageal cancer cells.

    Science.gov (United States)

    Abdel-Latif, Mohamed M; Inoue, Hiroyasu; Reynolds, John V

    2016-09-01

    Ursodeoxycholic acid (UDCA) was reported to reduce bile acid toxicity, but the mechanisms underlying its cytoprotective effects are not fully understood. The aim of the present study was to examine the effects of UDCA on the modulation of deoxycholic acid (DCA)-induced signal transduction in oesophageal cancer cells. Nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activity was assessed using a gel shift assay. NF-κB activation and translocation was performed using an ELISA-based assay and immunofluorescence analysis. COX-2 expression was analysed by western blotting and COX-2 promoter activity was assessed by luciferase assay. DCA induced NF-κB and AP-1 DNA-binding activities in SKGT-4 and OE33 cells. UDCA pretreatment inhibited DCA-induced NF-κB and AP-1 activation and NF-κB translocation. This inhibitory effect was coupled with a blockade of IκB-α degradation and inhibition of phosphorylation of IKK-α/β and ERK1/2. Moreover, UDCA pretreatment inhibited COX-2 upregulation. Using transient transfection of the COX-2 promoter, UDCA pretreatment abrogated DCA-induced COX-2 promoter activation. In addition, UDCA protected oesophageal cells from the apoptotic effects of deoxycholate. Our findings indicate that UDCA inhibits DCA-induced signalling pathways in oesophageal cancer cells. These data indicate a possible mechanistic role for the chemopreventive actions of UDCA in oesophageal carcinogenesis.

  6. The Effect of Public Service Advertising on Cardiovascular Disease in Korea.

    Science.gov (United States)

    Jang, Juhyun; Na, Baeg Ju; Lee, Moo-Sik; Seo, Soonryu; Sung, Changhyun; Kim, Hyun Joo; Lee, Jin Yong

    2016-08-01

    Public Service Advertising (PSA) is a public interest message disseminated in the form of an advertisement communication and its main purpose is to promote public behavioral changes regarding a social issue. Korea Centers for Disease Control and Prevention (KCDC) has been delivering PSA by various media. However, the effect of PSAs has never been evaluated. The purpose of this study was to estimate the effects of broadcasted PSA produced by KCDC on cardiovascular disease (CVD). One thousand adult participants throughout 15 provinces in Korea were chosen through the quota sampling method in 2012. A face-to-face research survey with 13 questions was conducted using a Computer Assisted Personal Interview (CAPI) system. Previous exposure to the PSA message, understanding, and behavioral intention to change was assessed. After watching the PSA, about 75% of participants answered that they could understand the contents well and 70% had willingness to change their behaviors associated with CVD. However, only 24% of participants answered they watched the PSA during the past year. The PSA had positive effects on increasing the level of understanding and intention to change behaviors regarding CVD. However, the level of exposure was low. KCDC should make an effort to increase the public exposure level, which could be an important success factor regarding the PSA. In addition, KCDC should consider customized PSA for vulnerable people such as multi-cultural families, the disabled, and the elderly.

  7. Distinct pathways to persuasion: The role of affect in message-framing effects

    NARCIS (Netherlands)

    Riet, J.P. van 't; Ruiter, R.A.C.; Werrij, M.Q.; Candel, M.J.J.M.; Vries, H. de

    2010-01-01

    Health-promoting messages can be framed in terms of the gains that are associated with healthy behaviour (gain frame) or the losses that are associated with unhealthy behaviour (loss frame). In the present research, we examined the role of positive and negative affect in the persuasive effects of

  8. Distinct pathways to persuasion: the role of affect in message-framing effects.

    NARCIS (Netherlands)

    Riet, van 't J.P.; Ruiter, R.A.C.; Werry, M.Q.; Candel, M.J.J.M.; Vries, de H.

    2010-01-01

    Health-promoting messages can be framed in terms of the gains that are associated with healthy behaviour (gain frame) or the losses that are associated with unhealthy behaviour (loss frame). In the present research, we examined the role of positive and negative affect in the persuasive effects of

  9. Studies on the pathways and effects of cadmium in controlled ecosystem enclosures

    Energy Technology Data Exchange (ETDEWEB)

    Kremling, K; Piuze, J; Von Brockel, K; Wong, C S

    1978-01-01

    Research report:At Controlled Ecosystem Pollution Experiment (CEPEX) at Saanich Inlet on Vancouver Island, Canada, cadmium was added to sea water enclosed in moored plastic containers to assess the metal's effect on marine phytoplankton. The test containers received 1.3

  10. Cytotoxic effects of TBBPA and its interactions with signalling pathways in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Strack, S.; Sander, M.; Detzel, T.; Krug, H.F. [Forschungszentrum Kalsruhe (Germany). Inst. fuer Toxikologie und Genetik; Kuch, B. [Stuttgart Univ. (Germany). Inst. fuer Siedlungswasserbau und Wasserguetewirtschaft

    2004-09-15

    Toxic effects of TBBPA published so far have been recently reviewed by Birnbaum and Staskal The LC{sub 50} indicating the acute toxicity in vivo due to a single oral dose in mice and rats were higher than 4 to 5 g/kg, however, systematically long-term in vivo studies are missing. Weak estrogenic effects have been described by Meerts et al., demonstrating for TBBPA less pronounced activity than for other brominated bisphenols. The same group described competitive interactions in vitro with human transthyretin (TTR). In binding affinity assays they could demonstrate that TBBPA binds to TTR ten times more effectively than T{sub 4}. However, the available toxicological data are still extremely limited. For a comprehensive risk assessment valid data are insufficient. The aim of this study was to evaluate possible cytotoxic effects, and to gain insights into the underlying molecular mechanisms respectively the corresponding cellular signalling processes. This approach would allow to identify sensitive end-points of cellular toxicological responses. For these molecular toxicological investigations established cell lines should be used, in order to have a suitable model for appropriate toxicological studies.

  11. Ameliorating Effect of Piperine on NO-cGMP Pathway in Stress ...

    African Journals Online (AJOL)

    ... dose of PP and SB-203580 enhanced effect of Piperine in stressed mice with no array on locomotor activity with direct influence on Nitric oxide. Piperine produced significant changes in Nitric oxide level which is pathophysiologic mediator(s) of depression, which validate the action of piperine on depression symptoms.

  12. Effects of Plants and Isolates of Celastraceae Family on Cancer Pathways.

    Science.gov (United States)

    Bukhari, Syed Nasir Abbas; Jantan, Ibrahim; Seyed, Mohamed Ali

    2015-01-01

    The evaluation of crude drugs of natural origin as sources of new effective anticancer agents continues to be important due to the lack of effective anticancer drugs currently used in practice which are generally accompanied with adverse effects at different levels of severity. The aim of this concise review is to gather existing literature on anticancer potential of extracts and compounds isolated from Celastraceae species. This review covers six genera (Maytenus, Tripterygium, Hippocratea, Gymnosporia, Celastrus and Austroplenckia) belonging to this family and their 33 isolates. Studies carried out by using different cell lines have shown remarkable indication of anticancer activity, however, only a restricted number of studies have been reported using in vivo tumor models. Some of the compounds, such as triptolide, celastrol and demethylzeylasteral from T. wilfordii, have been extensively studied on their mechanisms of action due to their potent activity on various cancer cell lines. Such promising lead compounds should generate considerable interest among scientists to improve their therapeutic potential with fewer side effects by molecular modification.

  13. Hydrogeology, chemical characteristics, and water sources and pathways in the zone of contribution of a public-supply well in San Antonio, Texas

    Science.gov (United States)

    Musgrove, MaryLynn; Fahlquist, Lynne; Stanton, Gregory P.; Houston, Natalie A.; Lindgren, Richard J.

    2011-01-01

    In 2001, the National Water-Quality Assessment (NAWQA) Program of the U.S. Geological Survey initiated a series of studies on the transport of anthropogenic and natural contaminants (TANC) to public-supply wells (PSWs). The main goal of the TANC project was to better understand the source, transport, and receptor factors that control contaminant movement to PSWs in representative aquifers of the United States. Regional- and local-scale study areas were selected from within existing NAWQA study units, including the south-central Texas Edwards aquifer. The local-scale TANC study area, nested within the regional-scale NAWQA study area, is representative of the regional Edwards aquifer. The PSW selected for study is within a well field of six production wells. Although a single PSW was initially selected, because of constraints of well-field operation, samples were collected from different wells within the well field for different components of the study. Data collected from all of the well-field wells were considered comparable because of similar well construction, hydrogeology, and geochemistry. An additional 38 PSWs (mostly completed in the confined part of the aquifer) were sampled throughout the regional aquifer to characterize water quality. Two monitoring well clusters, with wells completed at different depths, were installed to the east and west of the well field (the Zarzamora and Timberhill monitoring well clusters, respectively). One of the monitoring wells was completed in the overburden to evaluate potential hydrologic connectivity with the Edwards aquifer. Geophysical and flowmeter logs were collected from one of the well-field PSWs to determine zones of contribution to the wellbore. These contributing zones, associated with different hydrogeologic units, were used to select monitoring well completion depths and groundwater sample collection depths for depth-dependent sampling. Depth-dependent samples were collected from the PSW from three different

  14. Dual Inhibition of PI3K/AKT and MEK/ERK Pathways Induces Synergistic Antitumor Effects in Diffuse Intrinsic Pontine Glioma Cells

    Directory of Open Access Journals (Sweden)

    Y. Linda Wu

    2017-04-01

    Full Text Available Diffuse intrinsic pontine glioma (DIPG is a devastating disease with an extremely poor prognosis. Recent studies have shown that platelet-derived growth factor receptor (PDGFR and its downstream effector pathway, PI3K/AKT/mTOR, are frequently amplified in DIPG, and potential therapies targeting this pathway have emerged. However, the addition of targeted single agents has not been found to improve clinical outcomes in DIPG, and targeting this pathway alone has produced insufficient clinical responses in multiple malignancies investigated, including lung, endometrial, and bladder cancers. Acquired resistance also seems inevitable. Activation of the Ras/Raf/MEK/ERK pathway, which shares many nodes of cross talk with the PI3K/AKT pathway, has been implicated in the development of resistance. In the present study, perifosine, a PI3K/AKT pathway inhibitor, and trametinib, a MEK inhibitor, were combined, and their therapeutic efficacy on DIPG cells was assessed. Growth delay assays were performed with each drug individually or in combination. Here, we show that dual inhibition of PI3K/AKT and MEK/ERK pathways synergistically reduced cell viability. We also reveal that trametinib induced AKT phosphorylation in DIPG cells that could not be effectively attenuated by the addition of perifosine, likely due to the activation of other compensatory mechanisms. The synergistic reduction in cell viability was through the pronounced induction of apoptosis, with some effect from cell cycle arrest. We conclude that the concurrent inhibition of the PI3K/AKT and MEK/ERK pathways may be a potential therapeutic strategy for DIPG.

  15. Modelling and performance analysis of clinical pathways using the stochastic process algebra PEPA.

    Science.gov (United States)

    Yang, Xian; Han, Rui; Guo, Yike; Bradley, Jeremy; Cox, Benita; Dickinson, Robert; Kitney, Richard

    2012-01-01

    Hospitals nowadays have to serve numerous patients with limited medical staff and equipment while maintaining healthcare quality. Clinical pathway informatics is regarded as an efficient way to solve a series of hospital challenges. To date, conventional research lacks a mathematical model to describe clinical pathways. Existing vague descriptions cannot fully capture the complexities accurately in clinical pathways and hinders the effective management and further optimization of clinical pathways. Given this motivation, this paper presents a clinical pathway management platform, the Imperial Clinical Pathway Analyzer (ICPA). By extending the stochastic model performance evaluation process algebra (PEPA), ICPA introduces a clinical-pathway-specific model: clinical pathway PEPA (CPP). ICPA can simulate stochastic behaviours of a clinical pathway by extracting information from public clinical databases and other related documents using CPP. Thus, the performance of this clinical pathway, including its throughput, resource utilisation and passage time can be quantitatively analysed. A typical clinical pathway on stroke extracted from a UK hospital is used to illustrate the effectiveness of ICPA. Three application scenarios are tested using ICPA: 1) redundant resources are identified and removed, thus the number of patients being served is maintained with less cost; 2) the patient passage time is estimated, providing the likelihood that patients can leave hospital within a specific period; 3) the maximum number of input patients are found, helping hospitals to decide whether they can serve more patients with the existing resource allocation. ICPA is an effective platform for clinical pathway management: 1) ICPA can describe a variety of components (state, activity, resource and constraints) in a clinical pathway, thus facilitating the proper understanding of complexities involved in it; 2) ICPA supports the performance analysis of clinical pathway, thereby assisting

  16. Effectiveness of the toll-free line for public insurance programs.

    Science.gov (United States)

    Saunders, Cynthia M

    2005-03-01

    Toll-free lines for public insurance programs are a major point of entry to inquire about information. More than 1 million Californians are eligible for public insurance programs based on income but not yet enrolled. In 2000 and 2002, a "mystery-shopper" survey was conducted to ascertain overall effectiveness and interlanguage variation for information provided in Armenian, Cantonese, English, Farsi, Hmong, Khmer, Korean, Russian, Spanish, and Vietnamese. Although the 2002 study showed statistically significant improvements from 2000, many constructs remained problematic. In 2002, for example, statistically significant interlanguage variation was identified in discussing and checking eligibility for the program. Specifically, Spanish and Armenian callers were less likely than other language callers to have eligibility checked or deemed eligible. Removing barriers to enrollment in public insurance programs often requires political solutions, but improving customer service for the toll-free line necessitates efficiency and a focus on continuous quality improvement.

  17. Examination of the effects of public spending and trade policy on real exchange rate in Cameroon

    Directory of Open Access Journals (Sweden)

    Victalice Ngimanang ACHAMOH

    2015-11-01

    Full Text Available The study adopts the inter-temporal model of Rodríguez (1989 and Edward (1989 extended in Elbadawi and Soto (1997 to empirically examine the effect of public expenditure and trade openness on the real exchange rate using Cameroon data from 1977 to 2010. After exploring some issues on exchange rate and reviewing the relevant literature, the study employs residual based-cointegration technique. All the variables were stationary at level form or first differences. Public spending significantly appreciates the real exchange likewise the trade openness variable in the longrun. The results of the study suggests that appreciation of real exchange rate could be prevented by contracting public spending or adopting restrictive trade measures especially in the long run.

  18. To What Extent Should Public Corporations Be Consolidated? Considering the Effects on Public Deficit and Debt in Spanish Municipalities

    Directory of Open Access Journals (Sweden)

    Marta de VICENTE LAMA

    2018-02-01

    Full Text Available The consolidation perimeter of the public sector is the most important line between the micro and macro systems of government accounting. This paper focuses on the public sector boundary and assesses the potential impact on key reported figures – such as the ‘Maastricht’ deficit and debt ratios – that would result from moving public corporations inside the perimeter of the consolidated general government sector, public corporations that currently lie outside the general government sector. After examining 90 Spanish local governments with populations of over 50,000 during the 2010-2012 period, our results show that including public corporations within the general government sector perimeter leads to substantial differences in deficit and debt ratios, and that these differences significantly increase the number of municipalities in violation of fiscal limits imposed by the government. We also find that municipalities’ pre- and post-consolidation debt ratios are significantly different depending on the ruling party’s political ideology.   

  19. Economic evaluation of the air pollution effect on public health in China's 74 cities.

    Science.gov (United States)

    Li, Li; Lei, Yalin; Pan, Dongyan; Yu, Chen; Si, Chunyan

    2016-01-01

    Air deterioration caused by pollution has harmed public health. The existing studies on the economic loss caused by a variety of air pollutants in multiple cities are lacking. To understand the effect of different pollutants on public health and to provide the basis of the environmental governance for governments, based on the dose-response relation and the willingness to pay, this paper used the latest available data of the inhalable particulate matter (PM10) and sulphur dioxide (SO2) from January 2015 to June 2015 in 74 cities by establishing the lowest and the highest limit scenarios. The results show that (1) in the lowest and highest limit scenario, the health-related economic loss caused by PM10 and SO2 represented 1.63 and 2.32 % of the GDP, respectively; (2) For a single city, in the lowest and the highest limit scenarios, the highest economic loss of the public health effect caused by PM10 and SO2 was observed in Chongqing; the highest economic loss of the public health effect per capita occurred in Hebei Baoding. The highest proportion of the health-related economic loss accounting for GDP was found in Hebei Xingtai. The main reason is that the terrain conditions are not conducive to the spread of air pollutants in Chongqing, Baoding and Xingtai, and the three cities are typical heavy industrial cities that are based on coal resources. Therefore, this paper proposes to improve the energy structure, use the advanced production process, reasonably control the urban population growth, and adopt the emissions trading system in order to reduce the economic loss caused by the effects of air pollution on public health.

  20. Effects of Alternative Framing on the Publics Perceived Importance of Environmental Conservation

    Directory of Open Access Journals (Sweden)

    Amanda E Sorensen

    2015-05-01

    Full Text Available Effective communication of science to the general public is important for numerous reasons, including support for policy, funding, informed public decision making, among others. Prior research has found that scientists participating in public policy and public communication must frame their communication efforts in order to connect with audiences. A frame is the mechanism that individuals use to understand and interpret the world around them. Framing can encourage specific interpretations and reference points for a particular issue or event; especially when meaning is negotiated between the media and public audiences. In this study, we looked at the effect of framing within an environmental conservation context. To do this we had survey respondents rank common issues, among them being environmental conservation, from most important to least important for the government to address. We framed environmental conservation using three synonymous terms (environmental security, ecosystem services, and environmental quality to assess whether there was an effect on rankings dependent on how we framed environmental conservation. We also investigated the effect of individuals’ personality characteristics (identity frame on those environmental conservation rankings. We found that individuals who self-identified as environmentalist were positively associated with ranking highly (most important environmental conservation when it was framed as either environmental quality or ecosystem services, but not when it was framed as environmental security. Conversely, those individuals who did not rank themselves highly as self-identified environmentalists were positively associated with environmental conservation when it was framed as environmental security. This research suggests that framing audience specific messages can engender audience support in hot-button issues such as environmental conservation and climate change.

  1. Water quality management of contaminated areas and its effects on doses from aquatic pathways

    International Nuclear Information System (INIS)

    Voitsekhovitch, O.; Sansone, U.; Zhelesnyak, M.; Bugai, D.

    1996-01-01

    A critical analysis of remedial actions performed in the Chernobyl close zone are presented in term of effectiveness to dose reduction and money expenditure. The Chernobyl experience proved the need to consolidate the international water protection capacity on the basis of scientific knowledge which should exclude inefficient use of national resource. Strategical and technological interventions on water quality management need to be revised on the base of the experience gained after the 1986 accident. The lesson learned from the Chernobyl experience has to be used as a key element in the adoption of a strategy of water bodies management. Remedial actions have to be based with an integrated approach considering: dose reduction, secondary environmental effects of countermeasures, synergisms of radionuclides and countermeasure applications with other toxicants, social and economical factors of the contaminated areas

  2. Effectiveness of short-term psychodynamic group therapy in a public outpatient psychotherapy unit

    DEFF Research Database (Denmark)

    Jensen, Hans Henrik; Mortensen, Erik Lykke; Lotz, Martin

    2010-01-01

    BACKGROUND: Short-term psychodynamic group therapy in heterogeneous patient groups is common in the public Danish psychiatric system but is in need of evaluation. AIM: To investigate improvement in 39-session psychodynamic group therapy using three criteria: 1) effect size (Cohen's d), 2...... compared with Danish norms. Clinical implications: Patients referred to public outpatient treatment settings may need alternative or longer treatment than 39 sessions of psychodynamic group therapy over 3 months.......) and subscales. Analyses were conducted on the total sample and after exclusion of 32 GSI pre-treatment no-cases. RESULTS: The total sample GSI effect size was 0.74 indicating a moderate to large effect size (ranging from 0.67 in depressed to 0.74 in neurotic and personality disorder patients), which increased...

  3. Different goods, different effects: Exploring the roles of generalized trust in public goods provision

    DEFF Research Database (Denmark)

    Sønderskov, Kim

    -product situation (whether to buy organic food or not). This design provides a possibility to detect whether any effect of generalized trust is due to strategic behavior or due to altruistic motives among trusters. The results show that generalized trust enhances recycling significantly whereas it only has a very......This paper tests the hypothesis that generalized trust helps solve large-n collective action problems in a rationalistic framework. A rigors test is employed in that the hypothesis is tested in two different choice situations; a pure public good situation (whether to recycle or not) and a joint...... week positive effect on organic food consumption. Hence, generalized trust only affects public good provision when a collective action problem is present. The analyses thus sustain the hypothesis. It is furthermore concluded that the effect of generalized trust is due to strategic behavior...

  4. Double Crowding-Out Effects of Means-Tested Public Provision for Long-Term Care

    Directory of Open Access Journals (Sweden)

    Christophe Courbage

    2015-02-01

    Full Text Available Publicly provided long-term care (LTC insurance with means-tested benefits is suspected to crowd out either private saving or informal care. This contribution predicts crowding-out effects for both private saving and informal care for policy measures designed to relieve the public purse from LTC expenditure such as more stringent means testing and increased taxation of inheritance. These effects result from the interaction of a parent who decides on the amount of saving in retirement and a caregiver who decides on the effort devoted to informal care which lowers the probability of admission to a nursing home. Double crowding-out effects are also found to be the consequence of exogenous influences, notably a higher opportunity cost of caregiving.

  5. The Beagle 2 Effect - public response to the UK Mars lander

    Science.gov (United States)

    Pillinger, J. M.; Pillinger, C. T.

    As a prerequisite for understanding science, the target audience must first be aware of an issue and then continue to maintain interest. We discuss the impact of the Beagle 2 mission to Mars on raising awareness amongst the general public as the first step to increasing understanding of the scientific and technological challenges and solutions such a mission addresses. The massive amount of public interest created is now being ttributed to the so-called "Beagle 2 Effect". We consider the reasons why the public, particularly, but not exclusively, in the UK took Beagle 2 to heart. Initially our strategy, as part of the PR plan for Beagle 2, was to collate media coverage for various stages and discrete campaigns in particular to use press cuttings to determine the level of recognition of Beagle 2 as a brand. At the start of the project this information was to support sponsorship bids, latterly the intrinsic value of media, and hence public, awareness was recognised by the major partners in the project. Much of the subsequent public awareness resulted from the comprehensive coverage in all branches of the media. A second opportunity to evaluate the response to the mission was presented to us as it became increasingly clear that Beagle 2 was able to engage an audience much wider than that typically interested in space, or science in general. We highlighted how far mention of Beagle 2 has spread. Additionally numerous unsolicited letters have been received from the public and these have been collated to indicate the factors which appear to have contributed to the widespread interest in Beagle 2. It is not clear whether the "Beagle 2 Effect" can, or will, be transferred to subsequent space missions.

  6. Effects of reaction-kinetic parameters on modeling reaction pathways in GaN MOVPE growth

    Science.gov (United States)

    Zhang, Hong; Zuo, Ran; Zhang, Guoyi

    2017-11-01

    In the modeling of the reaction-transport process in GaN MOVPE growth, the selections of kinetic parameters (activation energy Ea and pre-exponential factor A) for gas reactions are quite uncertain, which cause uncertainties in both gas reaction path and growth rate. In this study, numerical modeling of the reaction-transport process for GaN MOVPE growth in a vertical rotating disk reactor is conducted with varying kinetic parameters for main reaction paths. By comparisons of the molar concentrations of major Ga-containing species and the growth rates, the effects of kinetic parameters on gas reaction paths are determined. The results show that, depending on the values of the kinetic parameters, the gas reaction path may be dominated either by adduct/amide formation path, or by TMG pyrolysis path, or by both. Although the reaction path varies with different kinetic parameters, the predicted growth rates change only slightly because the total transport rate of Ga-containing species to the substrate changes slightly with reaction paths. This explains why previous authors using different chemical models predicted growth rates close to the experiment values. By varying the pre-exponential factor for the amide trimerization, it is found that the more trimers are formed, the lower the growth rates are than the experimental value, which indicates that trimers are poor growth precursors, because of thermal diffusion effect caused by high temperature gradient. The effective order for the contribution of major species to growth rate is found as: pyrolysis species > amides > trimers. The study also shows that radical reactions have little effect on gas reaction path because of the generation and depletion of H radicals in the chain reactions when NH2 is considered as the end species.

  7. Improving the detection of pathways in genome-wide association studies by combined effects of SNPs from Linkage Disequilibrium blocks

    OpenAIRE

    Zhao, Huiying; Nyholt, Dale R.; Yang, Yuanhao; Wang, Jihua; Yang, Yuedong

    2017-01-01

    Genome-wide association studies (GWAS) have successfully identified single variants associated with diseases. To increase the power of GWAS, gene-based and pathway-based tests are commonly employed to detect more risk factors. However, the gene- and pathway-based association tests may be biased towards genes or pathways containing a large number of single-nucleotide polymorphisms (SNPs) with small P-values caused by high linkage disequilibrium (LD) correlations. To address such bias, numerous...

  8. Effects of Public Relations Activities on Customer Satisfaction in the University Libraries

    Directory of Open Access Journals (Sweden)

    Ayşe Gedikçi, Öndoğan

    2013-11-01

    Full Text Available Like all organizations in the process of globalization, university libraries also have focused on their customers much more in order to continue their existence and they have diversified their services in order to increase customer satisfaction. Customer satisfaction emerges as a result of integration of many interdependent components. In this study, public relations works, the most important factor affecting the customer satisfaction, are handled and it is tried to determine the effect of public relations works conducted at Selcuk University Central Library on the customer satisfaction. In the study used descriptive methods, data were obtained from all customer groups who came to the Central Library through questionnaire. It was come out that all customer groups who came to the Central Library were satisfied with public relations works related to the library's physical elements and service elements, but they were not content with public relations works conducted out of the organization in order to improve the customer relations. In consequence of the research, it was observed that the variable that customers gives more importance is the physical elements variable ( =3,86. The most intense relationship between variables is between service element with the physical elements (r=0,667, p<0,01 and public relations elements (r=0,642, p<0,0.

  9. Effectively engaging stakeholders and the public in developing violence prevention messages.

    Science.gov (United States)

    Boyko, Jennifer A; Wathen, C Nadine; Kothari, Anita

    2017-05-11

    Preventing family violence requires that stakeholders and the broader public be involved in developing evidence-based violence prevention strategies. However, gaps exist in between what we know (knowledge), what we do (action), and the structures supporting practice (policy). We discuss the broad challenge of mobilizing knowledge-for-action in family violence, with a primary focus on the issue of how stakeholders and the public can be effectively engaged when developing and communicating evidence-based violence prevention messages. We suggest that a comprehensive approach to stakeholder and public engagement in developing violence prevention messages includes: 1) clear and consistent messaging; 2) identifying and using, as appropriate, lessons from campaigns that show evidence of reducing specific types of violence; and 3) evidence-informed approaches for communicating to specific groups. Components of a comprehensive approach must take into account the available research evidence, implementation feasibility, and the context-specific nature of family violence. While strategies exist for engaging stakeholders and the public in messaging about family violence prevention, knowledge mobilization must be informed by evidence, dialogue with stakeholders, and proactive media strategies. This paper will be of interest to public health practitioners or others involved in planning and implementing violence prevention programs because it highlights what is known about the issue, potential solutions, and implementation considerations.

  10. The interaction of social networks and child obesity prevention program effects: the pathways trial.

    Science.gov (United States)

    Shin, Hee-Sung; Valente, Thomas W; Riggs, Nathaniel R; Huh, Jimi; Spruijt-Metz, Donna; Chou, Chih-Ping; Ann Pentz, Mary

    2014-06-01

    Social network analysis was used to examine whether peer influence from one's social networks moderates obesity prevention program effects on obesity-related behaviors: healthful and unhealthful. Participants included 557 children residing in Southern California. The survey assessed health-promoting behaviors (i.e., physical activity at school, physical activity outside of school, and fruit and vegetable intake), as well as unhealthful behaviors (high-calorie, low-nutrient intake and sedentary activity), and peer exposure calculated from social network nominations as indicators of peer influence. Multilevel models were conducted separately on outcomes predicted by program participation, peer exposure, and program participation by peer exposure. Results indicated that peer exposure was positively associated with one's own healthful and unhealthful behaviors. Program participation effects were moderated by peer influence, but only when unhealthful peer influence was present. Results suggest that peer influence can diminish or amplify prevention programs Future interventions should consider peer-led components to promote healthful influence of peers on healthful and unhealthful behaviors, and programs should be mindful that their effects are moderated by social networks. Copyright © 2014 The Obesity Society.

  11. Neuromodulatory Effect of Thymoquinone in Attenuating Glutamate-Mediated Neurotoxicity Targeting the Amyloidogenic and Apoptotic Pathways

    Directory of Open Access Journals (Sweden)

    Ibram Amin Fouad

    2018-04-01

    Full Text Available Overexposure of the glutamatergic N-methyl-d-aspartate (NMDA receptor to the excitatory neurotransmitter l-glutamic acid leads to neuronal cell death by excitotoxicity as a result of increased intracellular Ca2+, mitochondrial dysfunction, and apoptosis. Moreover, it was previously reported that prolonged activation of the NMDA receptor increased beta-amyloid (Aβ levels in the brain. Thymoquinone (TQ, the active constituent of Nigella sativa seeds, has been shown to have potent antioxidant and antiapoptotic effects. The aim of the present study was to explore the neuromodulatory effects of different doses of TQ (2.5 and 10 mg/kg against apoptotic cell death and Aβ formation resulting from glutamate administration in rats using vitamin E as a positive control. Behavioral changes were assessed using Y-maze and Morris water maze tests for evaluating spatial memory and cognitive functions. Caspase-3, Lactate dehydrogenase, Aβ-42, and cytochrome c gene expression were determined. TQ-treated groups showed significant decreases in the levels of all tested biochemical and behavioral parameters compared with the glutamate-treated group. These findings demonstrated that TQ has a promising neuroprotective activity against glutamate-induced neurotoxicity and this effect is mediated through its anti-amyloidogenic, antioxidant, and antiapoptotic activities.

  12. Pathway to neural resilience: Self-esteem buffers against deleterious effects of poverty on the hippocampus.

    Science.gov (United States)

    Wang, Yinan; Zhang, Lin; Kong, Xiangzhen; Hong, Yingyi; Cheon, Bobby; Liu, Jia

    2016-11-01

    Human neuroimaging studies have shown that people living in poverty tend to suffer hippocampal atrophy, which leads to impaired memory and learning throughout life. However, behavioral studies demonstrate that poor people with high self-esteem are often exempt from the deleterious effect of poverty and instead possess a happy and successful life. Here we investigated whether high self-esteem can buffer against the deleterious effects of poverty, as indicated by low subjective socioeconomic status (SSS), on the hippocampal gray matter volume (GMV) in a large cohort of young participants (N = 280). As expected, findings revealed that although low (vs. high) SSS was linked with a smaller hippocampal GMV, the deleterious effect of low SSS on hippocampal GMV was alleviated when the participants have high self-esteem. Commonality analyses further confirmed this observation. The current study suggests that positive psychological resources such as self-esteem may provide protection for the hippocampal atrophy in adversity. Hum Brain Mapp 37:3757-3766, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

    International Nuclear Information System (INIS)

    Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole; Testa, Mauro; Tang, Shikui; Gheorghiu, Liliana; Biggs, Peter; Paganetti, Harald; Efstathiou, Jason A.; Lu, Hsiao-Ming; Held, Kathryn D.; Willers, Henning

    2015-01-01

    Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and 137 Cs γ-rays were used. To estimate the RBE of protons relative to 60 Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation

  14. Lung Cancer Cell Line Screen Links Fanconi Anemia/BRCA Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Qi; Ghosh, Priyanjali; Magpayo, Nicole [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Testa, Mauro; Tang, Shikui [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Gheorghiu, Liliana [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Biggs, Peter; Paganetti, Harald [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Efstathiou, Jason A. [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lu, Hsiao-Ming [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Held, Kathryn D. [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Willers, Henning, E-mail: hwillers@mgh.harvard.edu [Laboratory of Cellular and Molecular Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2015-04-01

    Purpose: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. Methods and Materials: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/μm). For comparison, 250-kVp X rays and {sup 137}Cs γ-rays were used. To estimate the RBE of protons relative to {sup 60}Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. Results: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. Conclusions: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

  15. Improving the detection of pathways in genome-wide association studies by combined effects of SNPs from Linkage Disequilibrium blocks.

    Science.gov (United States)

    Zhao, Huiying; Nyholt, Dale R; Yang, Yuanhao; Wang, Jihua; Yang, Yuedong

    2017-06-14

    Genome-wide association studies (GWAS) have successfully identified single variants associated with diseases. To increase the power of GWAS, gene-based and pathway-based tests are commonly employed to detect more risk factors. However, the gene- and pathway-based association tests may be biased towards genes or pathways containing a large number of single-nucleotide polymorphisms (SNPs) with small P-values caused by high linkage disequilibrium (LD) correlations. To address such bias, numerous pathway-based methods have been developed. Here we propose a novel method, DGAT-path, to divide all SNPs assigned to genes in each pathway into LD blocks, and to sum the chi-square statistics of LD blocks for assessing the significance of the pathway by permutation tests. The method was proven robust with the type I error rate >1.6 times lower than other methods. Meanwhile, the method displays a higher power and is not biased by the pathway size. The applications to the GWAS summary statistics for schizophrenia and breast cancer indicate that the detected top pathways contain more genes close to associated SNPs than other methods. As a result, the method identified 17 and 12 significant pathways containing 20 and 21 novel associated genes, respectively for two diseases. The method is available online by http://sparks-lab.org/server/DGAT-path .

  16. Migration pathways in soils

    International Nuclear Information System (INIS)

    Gronow, J.R.

    1986-01-01

    This study looked at diffusive migration through three types of deformation; the projectile pathways, hydraulic fractures of the sediments and faults, and was divided into three experimental areas: autoradiography, the determination of diffusion coefficients and electron microscopy of model projectile pathways in clay. For the autoradiography, unstressed samples were exposed to two separate isotopes, Pm-147 (a possible model for Am behaviour) and the poorly sorbed iodide-125. The results indicated that there was no enhanced migration through deformed kaolin samples nor through fractured Great Meteor East (GME) sediment, although some was evident through the projectile pathways in GME and possibly through the GME sheared samples. The scanning electron microscopy of projectile pathways in clay showed that emplacement of a projectile appeared to have no effect on the orientation of particles at distances greater than two projectile radii from the centre of a projectile pathway. It showed that the particles were not simply aligned with the direction of motion of the projectile but that, the closer to the surface of a particular pathway, the closer the particles lay to their original orientation. This finding was of interest from two points of view: i) the ease of migration of a pollutant along the pathway, and ii) possible mechanisms of hole closure. It was concluded that, provided that there is no advective migration, the transport of radionuclides through sediments containing these defects would not be significantly more rapid than in undeformed sediments. (author)

  17. Exposure pathways and health effects associated with chemical and radiological toxicity of natural uranium: a review.

    Science.gov (United States)

    Brugge, Doug; de Lemos, Jamie L; Oldmixon, Beth

    2005-01-01

    Natural uranium exposure derives from the mining, milling, and processing of uranium ore, as well as from ingestion of groundwater that is naturally contaminated with uranium. Ingestion and inhalation are the primary routes of entry into the body. Absorption of uranium from the lungs or digestive track is typically low but can vary depending on compound specific solubility. From the blood, two-thirds of the uranium is excreted in urine over the first 24 hours and up to 80% to 90% of uranium deposited in the bone leaves the body within 1.5 years. The primary health outcomes of concern documented with respect to uranium are renal, developmental, reproductive, diminished bone growth, and DNA damage. The reported health effects derive from experimental animal studies and human epidemiology. The Lowest Observed Adverse Effect Level (LOAEL) derived from animal studies is 50 microg/m3 for inhalation and 60 ug/kg body weight/day for ingestion. The current respiratory standard of the Occupational Safety and Health Administration (OSHA), 50 microg/m3, affords no margin of safety. Considering the safety factors for species and individual variation, the ingestion LOAEL corresponds to the daily consumption set by the World Health Organization Drinking Water Standard at 2 microg/L. Based on economic considerations, the United States Environmental Protection Agency maximum contaminant level is 30 microg/L. Further research is needed, with particular attention on the impact of uranium on indigenous populations, on routes of exposure in communities near uranium sites, on the combined exposures present at many uranium sites, on human developmental defects, and on health effects at or below established exposure standards.

  18. Effects of pregnane glycosides on food intake depend on stimulation of the melanocortin pathway and BDNF in an animal model.

    Science.gov (United States)

    Komarnytsky, Slavko; Esposito, Debora; Rathinasabapathy, Thirumurugan; Poulev, Alexander; Raskin, Ilya

    2013-02-27

    Pregnane glycosides appear to modulate food intake by possibly affecting the hypothalamic feeding circuits; however, the mechanisms of the appetite-regulating effect of pregnane glycosides remain obscure. Here, we show that pregnane glycoside-enriched extracts from swamp milkweed Asclepias incarnata at 25-100 mg/kg daily attenuated food intake (up to 47.1 ± 8.5% less than controls) and body weight gain in rats (10% for males and 9% for females, respectively) by activating melanocortin signaling and inhibiting gastric emptying. The major milkweed pregnane glycoside, ikemagenin, exerted its appetite-regulating effect by decreasing levels of agouti-related protein (0.6-fold) but not NPY satiety peptides. Ikemagenin treatment also increased secretion of brain-derived neurotropic factor (BDNF) downstream of melanocortin receptors in the hypothalamus (1.4-fold) and in the C6 rat glioma cell culture in vitro (up to 6-fold). These results support the multimodal effects of pregnane glycosides on feeding regulation, which depends on the activity of the melanocortin signaling pathway and BDNF.

  19. Nephroprotective Effects of Polydatin against Ischemia/Reperfusion Injury: A Role for the PI3K/Akt Signal Pathway

    Directory of Open Access Journals (Sweden)

    Hong-Bao Liu

    2015-01-01

    Full Text Available Oxidative stress and inflammation are involved in the pathogenesis in renal ischemia/reperfusion (I/R injury. It has been demonstrated that polydatin processed the antioxidative, anti-inflammatory, and nephroprotective properties. However, whether it has beneficial effects and the possible mechanisms on renal I/R injury remain unclear. In our present study I/R models were simulated both in vitro and in vivo. Compared with vehicle control, the administration of polydatin significantly improved the renal function, accelerated the mitogenic response and reduced cell apoptosis in renal I/R injury models, strongly suppressed the I/R-induced upregulation of the expression of tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, inducible nitric oxide synthase, prostaglandin E-2, and nitric oxide levels, and dramatically decreased contents of malondialdehyde, but it increased the activity of superoxide dismutase, glutathione transferase, glutathione peroxidase and catalase, and the level of glutathione. Further investigation showed that polydatin upregulated the phosphorylation of Akt in kidneys of I/R injury dose-dependently. However, all beneficial effects of polydatin mentioned above were counteracted when we inhibited PI3K/Akt pathway with its specific inhibitor, wortmannin. Taken together, the present findings provide the first evidence demonstrating that PD exhibited prominent nephroprotective effects against renal I/R injury by antioxidative stress and inflammation through PI3-K/Akt-dependent molecular mechanisms.

  20. Neuroprotective effect of melatonin on soluble Aβ1-42-induced cortical neurodegeneration via Reelin-Dab1 signaling pathway.

    Science.gov (United States)

    Hu, Chunli; Wang, Pan; Zhang, Shuman; Ren, Lili; Lv, Yiheng; Yin, Rui; Bi, Jing

    2017-07-01

    Soluble Aβ 1-42 oligomers play a vital role in the development and pathogenesis of Alzheimer's disease (AD). Melatonin could delay the progress of AD through multiple mechanisms. Reelin-Dab1 signaling plays an important role in AD, including neuronal function and synaptic plasticity. However, whether melatonin could exert its neuroprotective function against soluble Aβ 1-42 -induced neurotoxicity during AD development through regulating Reelin-Dab1 signaling remains poorly understood. AD rat model was established by soluble Aβ 1-42 repeated intracerebroventricular injection. Using immunohistochemistry and Western blot analyses, the effect of melatonin on synaptic plasticity, neuritic degeneration, and astrocyte activation was investigated in cerebral cortex. Meanwhile, the expression of Reelin and Dab1 was also examined in cerebral cortex. In our in vitro study, Reelin-Dab1 signaling was inhibited by Reelin antibody, and neuroprotective effect of melatonin against Aβ 1-42 was further determined. Melatonin ameliorated the neurotoxiciy and astrocyte activation induced by Aβ 1-42 in the cerebral cortex. Melatonin also blocked the reduction in Reelin and Dab1 expression induced by Aβ 1-42 . Using in vitro study, Reelin inactivation completely abolished the protective effect of melatonin against Aβ 1-42 -induced neurotoxicity. Melatonin might play its neuroprotective role against Aβ 1-42 through mediating Reelin-Dab1 signaling pathway. Melatonin could be a safe and remarkable therapeutic candidate for AD and other aged-associated neurodegenerative diseases.

  1. Effects of sodium fluoride on MAPKs signaling pathway in the gills of a freshwater teleost, Cyprinus carpio.

    Science.gov (United States)

    Cao, Jinling; Chen, Jianjie; Wang, Jundong; Klerks, Paul; Xie, Lingtian

    2014-07-01

    Exposure to elevated levels of fluoride can cause a variety of adverse effects in fish. Previously we showed that fluoride causes injuries and apoptosis in the gills of Cyprinus carpio. In this study, the effects of fluoride on caspase-3 activity and on accumulation of proteins in the MAPKs pathways were evaluated using Western blotting and immunohistochemistry methods in vivo and in vitro. In vivo experiments showed that the caspase-3 activity increased with fluoride exposure level in a dose-dependent pattern Western blotting and immunohistochemistry results indicated that ERK relative activation tended to decrease as a function of fluoride exposure concentration. In contrast, relative activation of JNK increased with fluoride exposure level. Fluoride exposure did not appear to affect p38 activation. Furthermore, pretreatment of branchial cells with MAPK-specific inhibitors effectively prevented JNK induction and ERK inhibition, respectively, as well as reversed caspase-3 activity in fluoride-treated branchial cells. Our results indicate that activation of JNK and inactivation of ERK were caused by increased ROS and decreased antioxidant capacity in the gills of chronically exposed C. carpio described previously, which eventually caused the observed apoptosis in the fluoride-exposed gills and cells in C. carpio. JNK activation and ERK inactivation mechanism play a crucial role in gill impairment induced by chronic fluorosis. These findings contribute to a better understanding of the initial molecular and cellular events in the gill of fish chronically exposed to fluoride. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages.

    Science.gov (United States)

    Shoeb, Mohammad; Ramana, Kota V

    2012-01-01

    Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent antioxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study (U.C. Yadav et al., Free Radic. Biol. Med. 48:1423-1434, 2010) indicates a novel role for benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating arachidonic acid (AA) pathway-generated inflammatory lipid mediators in RAW264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes, prostaglandin E2, thromboxane 2 (TXB2), and prostacyclin (PGI2) in macrophages. Further, LPS-induced expression of AA-metabolizing enzymes such as COX-2, LOX-5, TXB synthase, and PGI2 synthase was significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-κB and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adduct formation. Most importantly, compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented LPS-induced macrophage death and monocyte adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of the COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Anti-Inflammatory Effects of Benfotiamine are Mediated Through the Regulation of Arachidonic Acid Pathway in Macrophages

    Science.gov (United States)

    Shoeb, Mohammad; Ramana, Kota V

    2011-01-01

    Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent anti-oxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study indicates a novel role of benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti-inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating the arachidonic acid (AA) pathway generated inflammatory lipid mediators in RAW 264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes (LTB4), prostaglandin E2 (PGE2), thromboxanes 2 (TXB2) and prostacyclin (PGI2) in macrophages. Further, LPS-induced expressions of AA metabolizing enzymes such as COX-2, LOX-5, TXB synthase and PGI2 synthase were significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-kB, and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adducts formation. Most importantly, as compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented the LPS-induced macrophage death and monocytes adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. PMID:22067901

  4. The Effect of Tianmai Xiaoke Pian on Insulin Resistance through PI3-K/AKT Signal Pathway

    Directory of Open Access Journals (Sweden)

    Nana Wang

    2016-01-01

    Full Text Available In the clinical setting, given the potential adverse effects of thiazolidinediones and biguanides, we often have difficulty in treatment that no other insulin sensitizers are available for use in type 2 diabetic mellitus (T2DM patients. Tianmai Xiaoke Pian (TMXKP is a traditional Chinese medicine tablet, which is comprised of chromium picolinate, Tianhuafen, Maidong, and Wuweizi. To understand its mechanism of action on insulin resistance, TMXKP (50 mg/kg orally was tested in T2DM rats (induced by a high-fat diet and streptozotocin. Eight weeks later, fasting blood glucose (FBG and oral glucose tolerance tests (OGTT were performed. Area under the curve (AUC and homeostatic model assessment of insulin resistance (HOMA-IR were calculated, and PI3-K/AKT signal pathway-related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR and western blot analysis in muscle, adipose, and liver tissues, respectively. TMXKP significantly reduced FBG, OGTT, AUC, and HOMA-IR in diabetic rats P<0.05. Furthermore, we also observed that TMXKP could significantly decrease IRS-1, IRS-2, PI3-K p85α, and AKT2 gene expression and also IRS-1, IRS-2, PI3-K, AKT2, and p-AKT2 protein expression levels P<0.05 in diabetic rats. These findings confirm that TMXKP can alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Thus TMXKP appears to be a promising insulin sensitizer.

  5. Deliberative public participation and hexachlorobenzene stockpiles.

    Science.gov (United States)

    Carson, Lyn

    2009-04-01

    This paper is concerned with the quality of citizen involvement in relation to the governance of industrial risks. Specifically, it explores the hexachlorobenzene (HCB) case relative to best practice public participation, which is consistent with deliberative democratic theory. The case could be judged a public participation failure given that the community committee in combination with the corporate sponsor was unable to agree on a mutually acceptable technological pathway. This stalemate might have been attributable in part to the time spent on the task of review. A diligent participation working party could have created a much more effective public participation plan, grounded in the core values of professional public participation practice.

  6. Uric acid demonstrates neuroprotective effect on Parkinson's disease mice through Nrf2-ARE signaling pathway.

    Science.gov (United States)

    Huang, Ting-Ting; Hao, Dong-Lin; Wu, Bo-Na; Mao, Lun-Lin; Zhang, Jin

    2017-12-02

    Uric acid has neuroprotective effect on Parkinson's disease (PD) by inhibiting oxidative damage and neuronal cell death. Our previous study has shown that uric acid protected dopaminergic cell line damage through inhibiting accumulation of NF-E2-related factor 2 (Nrf2). This study aimed to investigate its in vivo neuroprotective effect. PD was induced by MPTP intraperitoneally injection for 7 d in male C57BL/6 mice. Mice were treated with either uric acid (intraperitoneally injection 250 mg/kg) or saline for a total of 13 d. We showed that uric acid improved behavioral performances and cognition of PD mice, increased TH-positive dopaminergic neurons and decreased GFAP-positive astrocytes in substantia nigra (SN). Uric acid increased mRNA and protein expressions of Nrf2 and three Nrf2-responsive genes, including γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC), heme oxygenase-1 (HO-1) and NQO1. Uric acid significantly increased superoxide dismutase (SOD), CAT, glutathione (GSH) levels and decreased malondialdehyde (MDA) level in SN regions of MPTP-treated mice. Uric acid inhibited the hippocampal expression of IL-1β and decreased serum and hippocampus levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). In conclusion, uric acid demonstrates neuroprotective properties for dopaminergic neurons in PD mice through modulation of neuroinflammation and oxidative stress. Copyright © 2017. Published by Elsevier Inc.

  7. The effects of media on the level of accountability of public organization

    Directory of Open Access Journals (Sweden)

    Mehrdad Matani

    2014-09-01

    Full Text Available One of the features of democratic political systems is the accountability against their own performances. Media, one of the powerful elements of civil society and effectual on public thought, plays an important role in making the government responsive. To achieve this goal, the present study tries to investigate the effect of media on the improvement of the accountability level of the government agencies. The statistical society of this research includes all male students of Azad Ghaemshahr University where 320 students were selected through purposive sampling method based on Kerjesy and Morgan table. Applied research method is used in this survey. A researcher-made questionnaire was used to collect the required data. In order to validate the instrument, appropriate questions related to each variable were extracted from valid sources and finally approved by authorities. In order to calculate the reliability of the questionnaire, Cronbach’s alpha was calculated to be 89. Since the distribution of the data was normal, parametric statistical tests were used to testify the hypotheses. The findings of the study show that the media could be effective in terms of making public organizations responsive, through leading and training the public, unifying demands, and monitoring and broadcasting. However, the findings reveal that if the media were free and independent, they would better perform their responsibilities. Finally, the study at hand concludes that in comparison to other media, television is much more powerful in terms of pushing the public sector to be responsive.

  8. An improved public goods game model with reputation effect on the spatial lattices

    International Nuclear Information System (INIS)

    Zhou, Tianwei; Ding, Shuai; Fan, Wenjuan; Wang, Hao

    2016-01-01

    Highlights: • The reputation effect is added into the spatial public goods game model. • The individual utility is calculated as a combination of payoff and reputation. • The individual reputation will be adaptively modified as the system evolves. • The larger the reputation factor, the higher the cooperation level. - Abstract: How to model the evolution of cooperation within the population is an important and interdisciplinary issue across the academia. In this paper, we propose an improved public goods game model with reputation effect on spatial lattices to investigate the evolution of cooperation regarding the allocation of public resources. In our model, we modify the individual utility or fitness as a product of the present payoff and reputation-related power function, and strategy update adopts a Fermi-like probability function during the game evolution. Meanwhile, for an interaction between a pair of partners, the reputation of a cooperative agent will be accrued beyond two units, but the defective player will decrease his reputation by one unit. Extensive Monte Carlo numerical simulations indicate the introduction of reputation will foster the formation of cooperative clusters, and greatly enhance the level of public cooperation on the spatial lattices. The larger reputation factor leads to the higher cooperation level since the reputation effect will be enormously embedded into the utility evaluation under this scenario. The current results are vastly beneficial to understand the persistence and emergence of cooperation among many natural, social and synthetic systems, and also provide some useful suggestions to devise the feasible social governance measures and modes for the public resources or affairs.

  9. DMPD: Multifunctional effects of bradykinin on glial cells in relation to potentialanti-inflammatory effects. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17669557 Multifunctional effects of bradykinin on glial cells in relation to potent... Epub 2007 Jun 27. (.png) (.svg) (.html) (.csml) Show Multifunctional effects of bradykinin on glial cells i...n relation to potentialanti-inflammatory effects. PubmedID 17669557 Title Multifunction

  10. Environmental Public Health Tracking: a cost-effective system for characterizing the sources, distribution and public health impacts of environmental hazards.

    Science.gov (United States)

    Saunders, P J; Middleton, J D; Rudge, G

    2017-09-01

    The contemporary environment is a complex of interactions between physical, biological, socio-economic systems with major impacts on public health. However, gaps in our understanding of the causes, extent and distribution of these effects remain. The public health community in Sandwell West Midlands has collaborated to successfully develop, pilot and establish the first Environmental Public Health Tracking (EPHT) programme in Europe to address this 'environmental health gap' through systematically linking data on environmental hazards, exposures and diseases. Existing networks of environmental, health and regulatory agencies developed a suite of innovative methods to routinely share, integrate and analyse data on hazards, exposures and health outcomes to inform interventions. Effective data sharing and horizon scanning systems have been established, novel statistical methods piloted, plausible associations framed and tested, and targeted interventions informed by local concerns applied. These have influenced changes in public health practice. EPHT is a powerful tool for identifying and addressing the key environmental public health impacts at a local level. Sandwell's experience demonstrates that it can be established and operated at virtually no cost. The transfer of National Health Service epidemiological skills to local authorities in 2013 provides an opportunity to expand the programme to fully exploit its potential. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  11. Long-Run Effects of Public-Private Research Joint Ventures:

    DEFF Research Database (Denmark)

    Kaiser, Ulrich; Kuhn, Johan Moritz

    Subsidized research joint ventures (RJVs) between public research institutions and industry have become increasingly popular in Europe and the US. We study the long-run effects of such a support scheme that has been maintained by the Danish government since 1995. To cope with identification...... problems we apply nearest neighbor caliper matching and conditional difference-in-difference estimation methods. Our main findings are that (i) program participation effects are instant for annual patent applications and last for three years, (ii) employment effects materialize first after one year...

  12. Pathways to lean software development: An analysis of effective methods of change

    Science.gov (United States)

    Hanson, Richard D.

    This qualitative Delphi study explored the challenges that exist in delivering software on time, within budget, and with the original scope identified. The literature review identified many attempts over the past several decades to reform the methods used to develop software. These attempts found that the classical waterfall method, which is firmly entrenched in American business today was to blame for this difficulty (Chatterjee, 2010). Each of these proponents of new methods sought to remove waste, lighten out the process, and implement lean principles in software development. Through this study, the experts evaluated the barriers to effective development principles and defined leadership qualities necessary to overcome these barriers. The barriers identified were issues of resistance to change, risk and reward issues, and management buy-in. Thirty experts in software development from several Fortune 500 companies across the United States explored each of these issues in detail. The conclusion reached by these experts was that visionary leadership is necessary to overcome these challenges.

  13. Effects of introducing heterologous pathways on microbial metabolism with respect to metabolic optimality

    DEFF Research Database (Denmark)

    Kim, Hyun Uk; Kim, Byoungjin; Seung, Do Young

    2014-01-01

    reactions are more frequently introduced into various microbial hosts. The genome-scale metabolic simulations of Escherichia coli strains engineered to produce 1,4-butanediol, 1,3-propanediol, and amorphadiene suggest that microbial metabolism shows much different responses to the introduced heterologous...... reactions in a strain-specific manner than typical gene knockouts in terms of the energetic status (e.g., ATP and biomass generation) and chemical production capacity. The 1,4-butanediol and 1,3-propanediol producers showed greater metabolic optimality than the wild-type strains and gene knockout mutants...... for the energetic status, while the amorphadiene producer was metabolically less optimal. For the optimal chemical production capacity, additional gene knockouts were most effective for the strain producing 1,3-propanediol, but not for the one producing 1,4-butanediol. These observations suggest that strains having...

  14. Differential effects of ethanol on regional glutamatergic and GABAergic neurotransmitter pathways in mouse brain.

    Science.gov (United States)

    Tiwari, Vivek; Veeraiah, Pandichelvam; Subramaniam, Vaidyanathan; Patel, Anant Bahadur

    2014-03-01

    This study investigates the effects of ethanol on neuronal and astroglial metabolism using (1)H-[(13)C]-NMR spectroscopy in conjunction with infusion of [1,6-(13)C2]/[1-(13)C]glucose or [2-(13)C]acetate, respectively. A three-compartment metabolic model was fitted to the (13)C turnover of GluC3 , GluC4, GABAC 2, GABAC 3, AspC3 , and GlnC4 from [1,6-(13)C2 ]glucose to determine the rates of tricarboxylic acid (TCA) and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The ratio of neurotransmitter cycle to TCA cycle fluxes for glutamatergic and GABAegic neurons was obtained from the steady-state [2-(13)C]acetate experiment and used as constraints during the metabolic model fitting. (1)H MRS measurement suggests that depletion of ethanol from cerebral cortex follows zero order kinetics with rate 0.18 ± 0.04 μmol/g/min. Acute exposure of ethanol reduces the level of glutamate and aspartate in cortical region. GlnC4 labeling was found to be unchanged from a 15 min infusion of [2-(13)C]acetate suggesting that acute ethanol exposure does not affect astroglial metabolism in naive mice. Rates of TCA and neurotransmitter cycle associated with glutamatergic and GABAergic neurons were found to be significantly reduced in cortical and subcortical regions. Acute exposure of ethanol perturbs the level of neurometabolites and decreases the excitatory and inhibitory activity differentially across the regions of brain. Depletion of ethanol and its effect on brain functions were measured using (1)H and (1)H-[(13)C]-NMR spectroscopy in conjunction with infusion of (13)C-labeled substrates. Ethanol depletion from brain follows zero order kinetics. Ethanol perturbs level of glutamate, and the excitatory and inhibitory activity in mice brain. © 2013 International Society for Neurochemistry.

  15. What Difference Does Patient and Public Involvement Make and What Are Its Pathways to Impact? Qualitative Study of Patients and Researchers from a Cohort of Randomised Clinical Trials.

    Directory of Open Access Journals (Sweden)

    Louise Dudley

    Full Text Available Patient and public involvement (PPI is advocated in clinical trials yet evidence on how to optimise its impact is limited. We explored researchers' and PPI contributors' accounts of the impact of PPI within trials and factors likely to influence its impact.Semi-structured qualitative interviews with researchers and PPI contributors accessed through a cohort of randomised clinical trials. Analysis of transcripts of audio-recorded interviews was informed by the principles of the constant comparative method, elements of content analysis and informant triangulation.We interviewed 21 chief investigators, 10 trial managers and 17 PPI contributors from 28 trials. The accounts of informants within the same trials were largely in agreement. Over half the informants indicted PPI had made a difference within a trial, through contributions that influenced either an aspect of a trial, or how researchers thought about a trial. According to informants, the opportunity for PPI to make a difference was influenced by two main factors: whether chief investigators had goals and plans for PPI and the quality of the relationship between the research team and the PPI contributors. Early involvement of PPI contributors and including them in responsive (e.g. advisory groups and managerial (e.g. trial management groups roles were more likely to achieve impact compared to late involvement and oversight roles (e.g. trial steering committees.Those seeking to enhance PPI in trials should develop goals for PPI at an early stage that fits the needs of the trial, plan PPI implementation in accordance with these goals, invest in developing good relationships between PPI contributors and researchers, and favour responsive and managerial roles for contributors in preference to oversight-only roles. These features could be used by research funders in judging PPI in trial grant applications and to inform policies to optimise PPI within trials.

  16. SRS Public Involvement in Waste Management Has Resulted in Effective Decisions Supported by the Public Including Disposal Changes and Top-to-Bottom Review Initiative Consensus

    International Nuclear Information System (INIS)

    Goldston, W. T.; Villasor, H. P.

    2003-01-01

    In the Savannah River Site's (SRS') Solid Waste Management Program, a key to success is the Public Involvement Program. The Solid Waste Division at SRS manages the site's transuranic, low-level, mixed, and hazardous wastes. All decisions associated with management of this waste are of interest to the public and successful program implementation would be impossible without a vigorous public involvement program. The SRS Solid Waste Division (SWD) and its Department of Energy (DOE) customer developed, implemented, and maintain a comprehensive public participation and communications program. It is staffed by public participation and technical specialists to ensure information is presented in a manner that is technically accurate while being tailored for understanding by people without a technical background. The program provides the public with accurate, complete, timely information and early meaningful participation opportunities. It also fulfills the public participation activities required by laws, regulations, DOE Orders, and negotiated agreements. The primary goal of the SWD Public Participation Program is to fulfill the objectives of the SWD and SRS Strategic Plans to ''build trust and communicate openly, honestly, and responsibly with employees, customers, stakeholders, and regulators,'' and to ''work to extend the support of external stakeholders for the pursuit of SRS and DOE Complex business goals.'' This paper focuses on the public participation program goals, the implementation through formal plans and objectives, targeted waste management programs and specific audiences, and specific effects of the program on waste management activities. A discussion of the DOE and contractor teaming along with how plans are carried out is also included

  17. The effect of public social context on self-control: depletion for neuroticism and restoration for impression management.

    Science.gov (United States)

    Uziel, Liad; Baumeister, Roy F

    2012-03-01

    The present study explores the role of personality in moderating the effect of public social context on self-control. The authors predicted that in public settings neuroticism would be associated with ego-depletion effects and individual differences in impression management (IM) would be associated with restoration effects. Three experiments supported the hypothesis. In Study 1 neuroticism was associated with impaired self-control and IM was associated with enhanced self-control following an initial phase of working on a simple task in public (vs. in private). Study 2 replicated and extended these results to other domains of self-control. Study 3 explored whether public social context can cancel out early depletion effects. In this study, depleted participants engaged in a task that required self-control either alone or in public. As expected, the public settings were associated with restored self-control resources mostly among high IM individuals. Implications for self-control, neuroticism, and IM are discussed.

  18. Effects of Print Publication Lag in Dual Format Journals on Scientometric Indicators

    Science.gov (United States)

    Heneberg, Petr

    2013-01-01

    Background Publication lag between manuscript submission and its final publication is considered as an important factor affecting the decision to submit, the timeliness of presented data, and the scientometric measures of the particular journal. Dual-format peer-reviewed journals (publishing both print and online editions of their content) adopted a broadly accepted strategy to shorten the publication lag: to publish the accepted manuscripts online ahead of their print editions, which may follow days, but also years later. Effects of this widespread habit on the immediacy index (average number of times an article is cited in the year it is published) calculation were never analyzed. Methodology/Principal Findings Scopus database (which contains nearly up-to-date documents in press, but does not reveal citations by these documents until they are finalized) was searched for the journals with the highest total counts of articles in press, or highest counts of articles in press appearing online in 2010–2011. Number of citations received by the articles in press available online was found to be nearly equal to citations received within the year when the document was assigned to a journal issue. Thus, online publication of in press articles affects severely the calculation of immediacy index of their source titles, and disadvantages online-only and print-only journals when evaluating them according to the immediacy index and probably also according to the impact factor and similar measures. Conclusions/Significance Caution should be taken when evaluating dual-format journals supporting long publication lag. Further research should answer the question, on whether the immediacy index should be replaced by an indicator based on the date of first publication (online or in print, whichever comes first) to eliminate the problems analyzed in this report. Information value of immediacy index is further questioned by very high ratio of authors’ self-citations among the

  19. Technological innovation and its effect on public health in the United States

    Science.gov (United States)

    Gill, Preetinder Singh

    2013-01-01

    Background Good public health ensures an efficient work force. Organizations can ensure a prominent position on the global stage by staying on the leading edge of technological development. Public health and technological innovation are vital elements of prosperous economies. It is important to understand how these elements affect each other. This research study explored and described the relationship between these two critical elements/constructs. Methods Indicators representing technological innovation and public health were identified. Indicator data from 2000 to 2009 were collected from various US federal government sources, for the four US Census regions. The four US Census regions were then compared in terms of these indicators. Canonical correlation equations were formulated to identify combinations of the indicators that are strongly related to each other. Additionally, the cause–effect relationship between public health and technological innovation was described using the structural equation modeling technique. Results The four US Census regions ranked differently in terms of both type of indicators in a statistically significant manner. The canonical correlation analysis showed that the first set of canonical variables had a fairly strong relationship, with a magnitude > 0.65 at the 95% confidence interval, for all census regions. Structural equation modeling analysis provided β 12.98, for all census regions. The threshold Student’s t statistic was 1.98. Hence, it was found that the β values were significant at the 95% confidence interval, for all census regions. Discussion The results of the study showed that better technological innovation indicator scores were associated with better public health indicator scores. Furthermore, the study provided preliminary evidence that technological innovation shares causal relation with public health. PMID:23378771

  20. Pathways into Teaching: Q&A with Dr. Pam Grossman. REL Mid-Atlantic Teacher Effectiveness Webinar Series

    Science.gov (United States)

    Regional Educational Laboratory Mid-Atlantic, 2013

    2013-01-01

    This webinar explored several elements of teacher preparation pathways, including the history, popularity, and quality of various routes to certification, as well as the impact of these various pathways on teacher quality and retention and student achievement. This Q&A addressed the questions participants had for Dr. Grossman following the…

  1. Effects of EPSPS Copy Number Variation (CNV and Glyphosate Application on the Aromatic and Branched Chain Amino Acid Synthesis Pathways in Amaranthus palmeri

    Directory of Open Access Journals (Sweden)

    Manuel Fernández-Escalada

    2017-11-01

    Full Text Available A key enzyme of the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS; EC 2.5.1.19, is the known target of the widely used herbicide glyphosate. Glyphosate resistance in Amaranthus palmeri, one of the most troublesome weeds in agriculture, has evolved through increased EPSPS gene copy number. The aim of this work was to study the pleiotropic effects of (i EPSPS increased transcript abundance due to gene copy number variation (CNV and of (ii glyphosate application on the aromatic amino acid (AAA and branched chain amino acid (BCAA synthesis pathways. Hydroponically grown glyphosate sensitive (GS and glyphosate resistant (GR plants were treated with glyphosate 3 days after treatment. In absence of glyphosate treatment, high EPSPS gene copy number had only a subtle effect on transcriptional regulation of AAA and BCAA pathway genes. In contrast, glyphosate treatment provoked a general accumulation of the transcripts corresponding to genes of the AAA pathway leading to synthesis of chorismate in both GS and GR. After chorismate, anthranilate synthase transcript abundance was higher while chorismate mutase transcription showed a small decrease in GR and remained stable in GS, suggesting a regulatory branch point in the pathway that favors synthesis toward tryptophan over phenylalanine and tyrosine after glyphosate treatment. This was confirmed by studying enzyme activities in vitro and amino acid analysis. Importantly, this upregulation was glyphosate dose dependent and was observed similarly in both GS and GR populations. Glyphosate treatment also had a slight effect on the expression of BCAA genes but no general effect on the pathway could be observed. Taken together, our observations suggest that the high CNV of EPSPS in A. palmeri GR populations has no major pleiotropic effect on the expression of AAA biosynthetic genes, even in response to glyphosate treatment. This finding supports the idea that the fitness cost associated

  2. Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients.

    Science.gov (United States)

    Scaglia, Fernando; Carter, Susan; O'Brien, William E; Lee, Brendan

    2004-04-01

    Urea cycle disorders (UCDs) are a group of inborn errors of hepatic metabolism caused by the loss of enzymatic activities that mediate the transfer of nitrogen from ammonia to urea. These disorders often result in life-threatening hyperammonemia and hyperglutaminemia. A combination of sodium phenylbutyrate and sodium phenylacetate/benzoate is used in the clinical management of children with urea cycle defects as a glutamine trap, diverting nitrogen from urea synthesis to alternatives routes of excretion. We have observed that patients treated with these compounds have selective branched chain amino acid (BCAA) deficiency despite adequate dietary protein intake. However, the direct effect of alternative therapy on the steady state levels of plasma branched chain amino acids has not been well characterized. We have measured steady state plasma branched chain and other essential non-branched chain amino acids in control subjects, untreated ornithine transcarbamylase deficiency females and treated null activity urea cycle disorder patients in the fed steady state during the course of stable isotope studies. Steady-state leucine levels were noted to be significantly lower in treated urea cycle disorder patients when compared to either untreated ornithine transcarbamylase deficiency females or control subjects (Purea cycle disorder patients. These findings suggest that better titration of protein restriction could be achieved with branched chain amino acid supplementation in patients with UCDs who are on alternative route therapy.

  3. The clinician's guide to diagnostic imaging: Cost-effective pathways. Second edition

    International Nuclear Information System (INIS)

    Grossman, Z.D.; Chew, F.S.; Ellis, D.A.; Brigham, S.C.

    1987-01-01

    The authors developed a cost-effective approach to imaging studies, based on initial selection of an exam that best addresses the specific clinical problem and obviates the need for additional diagnostic tests. Tightly reasoned arguments compare available imaging options with respect to diagnostic yield, feasibility, risk, and cost. To aid the clinician in making cost comparisons, each paper of the Second Edition lists the dollar cost of relevant imaging studies. The Second Edition has been thoroughly revised to reflect the important advances in diagnostic imaging of the past three years, highlighting CT's expanding role in thoracic and abdominal problems, magnetic resonance imaging as a spectacular diagnostic tool for the central nervous system, and the clinical application of many newly-developed radiopharmaceuticals. New chapters cover breast cancer screening, acute spinal trauma, search for primary cancer of unknown origin, acute anuria, blunt chest trauma, new onset seizures, and spinal cord compression from metastases. Other papers have been rewritten for greater clarity and to incorporate new techniques, like dipyridamole stress testing. A glossary and an introduction define and explain the capabilities and limitations of current techniques

  4. Interpersonal communication as an indirect pathway for the effect of antismoking media content on smoking cessation.

    Science.gov (United States)

    van den Putte, Bas; Yzer, Marco; Southwell, Brian G; de Bruijn, Gert-Jan; Willemsen, Marc C

    2011-05-01

    In the context of health campaigns, interpersonal communication can serve at least 2 functions: (a) to stimulate change through social interaction and (b) in a secondary diffusion process, to further disseminate message content. In a 3-wave prospective study of 1,079 smokers, the authors demonstrate that mass media messages (antismoking campaigns and news coverage relevant to smoking cessation) have an indirect effect on smoking cessation intention and behavior via interpersonal communication. Exposure to campaigns and news coverage prompts discussion about the campaigns, and, in turn, about smoking cessation. Interpersonal communication regarding smoking cessation then influences intention to quit smoking and attempts to quit smoking. The study finds evidence not only for the social interaction function of interpersonal communication, but also for the secondary diffusion function. A substantial number of smokers who are not directly exposed to the antismoking campaigns are nevertheless indirectly exposed via communication with people who have seen these campaigns. These results imply that encouragement of interpersonal communication can be an important campaign objective.

  5. Effect of mammalian kidney osmolytes on the folding pathway of sheep serum albumin.

    Science.gov (United States)

    Dar, Mohammad Aasif; Islam, Asimul; Hassan, Md Imtaiyaz; Ahmad, Faizan

    2017-04-01

    Recently, we had published that urea-induced denaturation curves of optical properties of sheep serum albumin (SSA) are biphasic with a stable intermediate that has characteristics of molten globule (MG) state. In this study, we have extended the work by carrying out urea- and guanidinium chloride (GdmCl)-induced denaturations of SSA in the presence of naturally occurring mammalian kidney osmolytes, namely, sorbitol, myo-inositol and glycine betaine. We have observed that all these osmolytes (i) transform this biphasic transition into a co-operative, two-state transition and (ii) increase the stability of the protein in terms of midpoint of denaturation (C m ) and Gibbs free energy change in the absence of both denaturants (ΔG D 0 ). The relative effectiveness of different osmolytes on the stability of SSA follows the order: glycine betaine>myo-inositol>sorbitol. In this paper, we also report that kidney osmolytes destabilize MG state by shifting the equilibrium, native state↔MG state toward the left. This study will be helpful in understanding the existence of osmolytes in kidney and their role in folding of kidney proteins soaked with urea. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Publication Bias in Psychology: A Diagnosis Based on the Correlation between Effect Size and Sample Size

    Science.gov (United States)

    Kühberger, Anton; Fritz, Astrid; Scherndl, Thomas

    2014-01-01

    Background The p value obtained from a significance test provides no information about the magnitude or importance of the underlying phenomenon. Therefore, additional reporting of effect size is often recommended. Effect sizes are theoretically independent from sample size. Yet this may not hold true empirically: non-independence could indicate publication bias. Methods We investigate whether effect size is independent from sample size in psychological research. We randomly sampled 1,000 psychological articles from all areas of psychological research. We extracted p values, effect sizes, and sample sizes of all empirical papers, and calculated the correlation between effect size and sample size, and investigated the distribution of p values. Results We found a negative correlation of r = −.45 [95% CI: −.53; −.35] between effect size and sample size. In addition, we found an inordinately high number of p values just passing the boundary of significance. Additional data showed that neither implicit nor explicit power analysis could account for this pattern of findings. Conclusion The negative correlation between effect size and samples size, and the biased distribution of p values indicate pervasive publication bias in the entire field of psychology. PMID:25192357

  7. Theory-based approaches to understanding public emergency preparedness: implications for effective health and risk communication.

    Science.gov (United States)

    Paek, Hye-Jin; Hilyard, Karen; Freimuth, Vicki; Barge, J Kevin; Mindlin, Michele

    2010-06-01

    Recent natural and human-caused disasters have awakened public health officials to the importance of emergency preparedness. Guided by health behavior and media effects theories, the analysis of a statewide survey in Georgia reveals that self-efficacy, subjective norm, and emergency news exposure are positively associated with the respondents' possession of emergency items and their stages of emergency preparedness. Practical implications suggest less focus on demographics as the sole predictor of emergency preparedness and more comprehensive measures of preparedness, including both a person's cognitive stage of preparedness and checklists of emergency items on hand. We highlight the utility of theory-based approaches for understanding and predicting public emergency preparedness as a way to enable more effective health and risk communication.

  8. Are EM's communication tools effective? Evaluation research of two EM publications

    International Nuclear Information System (INIS)

    Wight, Evelyn; Gardner, Gene; Harvey, Tony

    1992-01-01

    As a reflection of its growing culture of openness, and in response to the public's need for accurate information about its activities, the U.S. Department of Energy (DOE) Office of the Assistant Secretary for Environmental Restoration and Waste Management (EM) has increased the amount of information available to the public through communication tools such as brochures, fact sheets, and a travelling exhibit with an interactive computer display. Our involvement with this effort has been to design, develop, and critique booklets, brochures, fact sheets and other communication tools for EM. This paper presents an evaluation of the effectiveness of two communication tools we developed: the EM Booklet and the EM Fact Sheets. We measured effectiveness using non-parametric testing. This paper describes DOE's culture change, EM's communication tools and their context within DOE'S new open culture, our research, test methods and results, the significance of our research, and our plans for future research. (author)

  9. The effectiveness of knowledge translation strategies used in public health: a systematic review

    Directory of Open Access Journals (Sweden)

    LaRocca Rebecca

    2012-09-01

    Full Text Available Abstract Background Literature related to the effectiveness of knowledge translation (KT strategies used in public health is lacking. The capacity to seek, analyze, and synthesize evidence-based information in public health is linked to greater success in making policy choices that have the best potential to yield positive outcomes for populations. The purpose of this systematic review is to identify the effectiveness of KT strategies used to promote evidence-informed decision making (EIDM among public health decision makers. Methods A search strategy was developed to identify primary studies published between 2000–2010. Studies were obtained from multiple electronic databases (CINAHL, Medline, EMBASE, and the Cochrane Database of Systematic Reviews. Searches were supplemented by hand searching and checking the reference lists of included articles. Two independent review authors screened studies for relevance, assessed methodological quality of relevant studies, and extracted data from studies using standardized tools. Results After removal of duplicates, the search identified 64, 391 titles related to KT strategies. Following title and abstract review, 346 publications were deemed potentially relevant, of which 5 met all relevance criteria on full text screen. The included publications were of moderate quality and consisted of five primary studies (four randomized controlled trials and one interrupted time series analysis. Results were synthesized narratively. Simple or single KT strategies were shown in some circumstances to be as effective as complex, multifaceted ones when changing practice including tailored and targeted messaging. Multifaceted KT strategies led to changes in knowledge but not practice. Knowledge translation strategies shown to be less effective were passive and included access to registries of pre-processed research evidence or print materials. While knowledge brokering did not have a significant effect generally

  10. Effect of stratum corneum heterogeneity, anisotropy, asymmetry and follicular pathway on transdermal penetration.

    Science.gov (United States)

    Barbero, Ana M; Frasch, H Frederick

    2017-08-28

    The impact of the complex structure of the stratum corneum on transdermal penetration is not yet fully described by existing models. A quantitative and thorough study of skin permeation is essential for chemical exposure assessment and transdermal delivery of drugs. The objective of this study is to analyze the effects of heterogeneity, anisotropy, asymmetry, follicular diffusion, and location of the main barrier of diffusion on percutaneous permeation. In the current study, the solution of the transient diffusion through a two-dimensional-anisotropic brick-and-mortar geometry of the stratum corneum is obtained using the commercial finite element program COMSOL Multiphysics. First, analytical solutions of an equivalent multilayer geometry are used to determine whether the lipids or corneocytes constitute the main permeation barrier. Also these analytical solutions are applied for validations of the finite element solutions. Three illustrative compounds are analyzed in these sections: diethyl phthalate, caffeine and nicotine. Then, asymmetry with depth and follicular diffusion are studied using caffeine as an illustrative compound. The following findings are drawn from this study: the main permeation barrier is located in the lipid layers; the flux and lag time of diffusion through a brick-and-mortar geometry are almost identical to the values corresponding to a multilayer geometry; the flux and lag time are affected when the lipid transbilayer diffusivity or the partition coefficients vary with depth, but are not affected by depth-dependent corneocyte diffusivity; and the follicular contribution has significance for low transbilayer lipid diffusivity, especially when flux between the follicle and the surrounding stratum corneum is involved. This study demonstrates that the diffusion is primarily transcellular and the main barrier is located in the lipid layers. Published by Elsevier B.V.

  11. Unique sex- and age-dependent effects in protective pathways in acute kidney injury.

    Science.gov (United States)

    Boddu, Ravindra; Fan, Chunlan; Rangarajan, Sunil; Sunil, Bhuvana; Bolisetty, Subhashini; Curtis, Lisa M

    2017-09-01

    Sex and age influence susceptibility to acute kidney injury (AKI), with young females exhibiting lowest incidence. In these studies, we investigated mechanisms which may underlie the sex/age-based dissimilarities. Cisplatin (Cp)-induced AKI resulted in morphological evidence of injury in all groups. A minimal rise in plasma creatinine (PCr) was seen in Young Females, whereas in Aged Females, PCr rose precipitously. Relative to Young Males, Aged Males showed significantly, but temporally, comparably elevated PCr. Notably, Aged Females showed significantly greater mortality, whereas Young Females exhibited none. Tissue KIM-1 and plasma NGAL were significantly lower in Young Females than all others. IGFBP7 levels were modestly increased in both Young groups. IGFBP7 levels in Aged Females were significantly elevated at baseline relative to Aged Males, and increased linearly through day 3 , when these levels were comparable in both Aged groups. Plasma cytokine levels similarly showed a pattern of protective effects preferentially in Young Females. Expression of the drug transporter MATE2 did not explain the sex/age distinctions. Heme oxygenase-1 (HO-1) levels (~28-kDa species) showed elevation at day 1 in all groups with highest levels seen in Young Males. Exclusively in Young Females, these levels returned to baseline on day 3 , suggestive of a more efficient recovery. In aggregate, we demonstrate, for the first time, a distinctive pattern of response to AKI in Young Females relative to males which appears to be significantly altered in aging. These distinctions may offer novel targets to exploit therapeutically in both females and males in the treatment of AKI.

  12. Protective effect of lycopene on fluoride-induced ameloblasts apoptosis and dental fluorosis through oxidative stress-mediated Caspase pathways.

    Science.gov (United States)

    Li, Weishan; Jiang, Binghua; Cao, Xianglin; Xie, Yongjiang; Huang, Ting

    2017-01-05

    Fluoride is an environmental toxicant and induces dental fluorosis and oxidative stress. Lycopene (LYC) is an effective antioxidant that is reported to attenuate fluoride toxicity. To determine the effects of LYC on sodium fluoride (NaF) -induced teeth and ameloblasts toxicity, rats were treated with NaF (10 mg/kg) and/or LYC (10 mg/kg) by orally administration for 5 weeks; ameloblasts were treated with NaF (5 mM) and/or LYC (2 μM) for 6 h. We found that the concentrations of fluoride, malondialdehyde (MDA) and reactive oxygen species (ROS), gene expressions and activities of Caspase-9 and Caspase-3, and the gene expressions of Bax were significantly decreased, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX), the gene expression of Bcl-2 were significantly increased in the LYC + NaF-treated rats group; concentrations of MDA and ROS, gene expressions and activities of Caspase-9 and Caspase-3, and the gene expression of Bax, and ameloblasts apoptosis rate were significantly decreased, while the activities of SOD and GPX, the gene expression of Bcl-2 were significantly increased in the LYC + NaF-treated ameloblasts group. These results suggest that LYC significantly combated NaF-induced ameloblasts apoptosis and dental fluorosis by attenuation oxidative stress and down-regulation Caspase pathway. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Effect of Botulinum Toxin Type A on TGF-β/Smad Pathway Signaling: Implications for Silicone-Induced Capsule Formation.

    Science.gov (United States)

    Kim, Sena; Ahn, Moonsang; Piao, Yibo; Ha, Yooseok; Choi, Dae-Kyoung; Yi, Min-Hee; Shin, Nara; Kim, Dong Woon; Oh, Sang-Ha

    2016-11-01

    One of the most serious complications of breast surgery using implants is capsular contracture. Several preventive treatments have been introduced; however, the mechanism of capsule formation has not been resolved completely. The authors previously identified negative effects of botulinum toxin type A on capsule formation, expression of transforming growth factor (TGF)-β1, and differentiation of fibroblasts into myofibroblasts. Thus, the authors investigated how to prevent capsule formation by using botulinum toxin type A, particularly by means of TGF-β1 signaling, in human fibroblasts. In vitro, cultured human fibroblasts were treated with TGF-β1 and/or botulinum toxin type A. Expression of collagen, matrix metalloproteinase, and Smad was examined by Western blotting. The activation of matrix metalloproteinase was observed by gelatin zymography. In vivo, the effect of botulinum toxin type A on the phosphorylation of Smad2 in silicone-induced capsule formation was evaluated by immunocytochemistry. In vitro, the phosphorylation of Smad2 was inhibited by botulinum toxin type A treatment. The expression levels of collagen types 1 and 3 were inhibited by botulinum toxin type A treatment, whereas those of matrix metalloproteinase-2 and matrix metalloproteinase-9 were enhanced. Gelatin zymography experiments confirmed enhanced matrix metalloproteinase-2 activity in collagen degradation. In vivo, botulinum toxin type A treatment reduced capsule thickness and Smad2 phosphorylation in silicone-induced capsules. This study suggests that botulinum toxin type A plays an important role in the inhibition of capsule formation through the TGF-β/Smad signaling pathway. Therapeutic, V.

  14. Longitudinal pathways from marital hostility to child anger during toddlerhood: genetic susceptibility and indirect effects via harsh parenting.

    Science.gov (United States)

    Rhoades, Kimberly A; Leve, Leslie D; Harold, Gordon T; Neiderhiser, Jenae M; Shaw, Daniel S; Reiss, David

    2011-04-01

    We examined direct and indirect pathways from marital hostility to toddler anger/frustration via harsh parenting and parental depressive symptoms, with an additional focus on the moderating role of genetic influences as inferred from birth parent anger/frustration. Participants were 361 linked triads of birth mothers, adoptive parents, and adopted children who were 9 (T1) and 18 (T2) months old across the study period. Results indicated an indirect effect from T1 marital hostility to T2 toddler anger/frustration via T2 parental harsh discipline. Results also indicated that the association between marital hostility and toddler anger was moderated by birth mother anger/frustration. For children whose birth mothers reported high levels of anger/frustration, adoptive parents' marital hostility at T1 predicted toddler anger/frustration at T2. This relation did not hold for children whose birth mothers reported low levels of anger/frustration. The results suggest that children whose birth mothers report elevated frustration might inherit an emotional lability that makes them more sensitive to the effects of marital hostility.

  15. The Effect of the Global Financial Crisis and the Sovereign Debt Crisis on Public Sector Accounting: A Contextual Analysis

    OpenAIRE

    Emmanuel Igbawase Abanyam; Paul Aondona Angahar

    2015-01-01

    This paper examines the effect of global financial crisis and the sovereign debt crisis on public sector accounting. The global financial crisis and sovereign debt crisis were contextually analysed bringing out clearly its effect on public sector accounting which include accounting issues related to public sector intervention, accounting for recapitalization of investment, accounting for fiscal support, accounting for financial guarantees. The paper found out that, the unresolved fiscal and d...

  16. The Effect of Gender on Job Satisfaction of Academic Staff in Malaysian Public Universities

    OpenAIRE

    Ma’rof Bin Redzuan, Haslinda Abdullah, Aida Mehrad, Hanina Halimatussadiah

    2015-01-01

    Based on last due decades, job satisfaction assumed as one of the imperative organizational factors that has great role among staff at workplace; furthermore,focusing on this important factor and finding effective items that impact on the level of job satisfaction is very essential. The main purpose of this research is to examine the relationship between gender and job satisfaction of academic staff at public universities in Malaysia. The Job Descriptive Index inventory (JDI) was used to mea...

  17. International economy. 82, controlling greenhouse effect: the stake of the international public policy

    International Nuclear Information System (INIS)

    Godard, O.; Oliveira-Martins, J.; Sgard, J.

    2000-01-01

    The greenhouse effect is one of the first stake of public policy which needs to be considered at the worldwide level. The climate changes shade doubts on the economic growth strategies adopted by all countries, and, if no major effort is made in the mastery of energy demand, worldwide greenhouse gas emissions will rapidly reach dangerous thresholds. This book gives a status of the research carried out on the economical impact of these policies. (J.S.)

  18. Acts of Atrocity: Effects on Public Opinion Support During War or Conflict

    Science.gov (United States)

    2007-12-01

    while] general public disenchantment, however, seems to have been largely practical , springing from the failure of our substantial military...have much effect on the majority of Americans focused on more practical measures for determining their support or opposition for the Vietnam War...of male detainees to masturbate while being photographed and videotaped; arranging naked male detainees in a pile and then jumping on them

  19. Inhibitory effects of ginseng total saponin on up-regulation of cAMP pathway induced by repeated administration of morphine.

    Science.gov (United States)

    Seo, Jeong-Ju; Lee, Jae-Woong; Lee, Wan-Kyu; Hong, Jin-Tae; Lee, Chong-Kil; Lee, Myung-Koo; Oh, Ki-Wan

    2008-02-01

    We have reported that ginseng total saponin (GTS) inhibited the development of physical and psychological dependence on morphine. However, the possible molecular mechanisms of GTS are unclear. Therefore, this study was undertaken to understand the possible molecular mechanism of GTS on the inhibitory effects of morphine-induced dependence. It has been reported that the up-regulated cAMP pathway in the LC of the mouse brain after repeated administration of morphine contributes to the feature of withdrawals. GTS inhibited up-regulation of cAMP pathway in the LC after repeated administration of morphine in this experiment. GTS inhibited cAMP levels and protein expression of protein kinase A (PKA). In addition, GTS inhibited the increase of cAMP response element binding protein (CREB) phosphorylation. Therefore, we conclude that the inhibitory effects of GTS on morphine-induced dependence might be mediated by the inhibition of cAMP pathway.

  20. Renoprotective Effect of Danhong Injection on Streptozotocin-Induced Diabetic Rats through a Peroxisome Proliferator-Activated Receptor γ Mediated Pathway

    Directory of Open Access Journals (Sweden)

    Xue Yang

    2018-01-01

    Full Text Available The aim of the study was to investigate the protective effect of Danhong injection (DHI on diabetic kidney disease and explore the potential mechanisms. Diabetic kidney disease was induced by unilateral nephrectomy, high