Targeting the glycoprotein 130 receptor subunit to control pain and inflammation

The glycoprotein 130 (gp130) is a shared signal-transducing-membrane-associated receptor for several hematopoietic cytokines. Its activation is implicated in pain and in a variety of diseases via signaling of proinflammatory cytokines. These include interleukin-6 (IL-6) subfamily cytokines, many of which play important roles in the pathogenesis of diseases such as rheumatoid arthritis, Castleman's disease, and Kaposi's sarcoma. Several strategies have been developed to block gp130-receptor-mediated signaling. These include the application of monoclonal antibodies, the creation of mutant form(s) of the gp130 with increased binding affinity for such ligands as IL-6/sIL-6R complex, and the generation of antagonists by selective mutagenesis of the specific cytokine/gp130 receptor binding site(s). Other strategies include targeting gp130-mediated signaling pathways such as that involving signal transducer and activator of transcription-3. This review provides a summary of the latest research pertaining to the role of gp130 in the pathogenesis of inflammatory and other diseases in which the gp130 receptor is implicated. An overview of antagonists targeting the gp130 receptor is included with particular emphasis on their mechanism of action and their limitations and potential for therapeutic application.

Shared action spaces:a basis function framework for social re-calibration of sensorimotor representations supporting joint action

The article explores the possibilities of formalizing and explaining the mechanisms that support spatial and social perspective alignment sustained over the duration of a social interaction. The basic proposed principle is that in social contexts the mechanisms for sensorimotor transformations and multisensory integration (learn to) incorporate information relative to the other actor(s), similar to the "re-calibration" of visual receptive fields in response to repeated tool use. This process aligns or merges the co-actors' spatial representations and creates a "Shared Action Space" (SAS) supporting key computations of social interactions and joint actions; for example, the remapping between the coordinate systems and frames of reference of the co-actors, including perspective taking, the sensorimotor transformations required for lifting jointly an object, and the predictions of the sensory effects of such joint action. The social re-calibration is proposed to be based on common basis function maps (BFMs) and could constitute an optimal solution to sensorimotor transformation and multisensory integration in joint action or more in general social interaction contexts. However, certain situations such as discrepant postural and viewpoint alignment and associated differences in perspectives between the co-actors could constrain the process quite differently. We discuss how alignment is achieved in the first place, and how it is maintained over time, providing a taxonomy of various forms and mechanisms of space alignment and overlap based, for instance, on automaticity vs. control of the transformations between the two agents. Finally, we discuss the link between low-level mechanisms for the sharing of space and high-level mechanisms for the sharing of cognitive representations. © 2013 Pezzulo, Iodice, Ferraina and Kessler.

Institutional contradiction and management control innovation:a field study of total quality management practices in a privatised telecommunications company

The purpose of this paper is to theorise the changes surrounding the introduction of a management control innovation, total quality management (TQM) techniques, within Telecom Fiji Limited. Using institutional theory and drawing on empirical evidence from multiple sources including interviews, discussions and documents, the paper explicates the institutionalization of these TQM practices. The focus of the paper is the micro-processes and practice changes around TQM implementation, rather than the influence of the macro-level structures that are often linked with institutional theory. The change agents used Quality Action Teams and the National Quality Council to introduce new TQM routines. The present study extends the scope of institutional analysis by explaining how institutional contradictions impact to create and make space for institutional entrepreneurs, who in turn, modify existing routines or introduce new routines in fluid organizational environments which also exhibit evidence of resistance.

Differential control of two forms of glutamate release by group III metabotropic glutamate receptors at rat entorhinal synapses

Neurotransmitter release at CNS synapses occurs via both action potential-dependent and independent mechanisms, and it has generally been accepted that these two forms of release are regulated in parallel. We examined the effects of activation of group III metabotropic glutamate receptors (mGluRs) on stimulus-evoked and spontaneous glutamate release onto entorhinal cortical neurones in rats, and found a differential regulation of action potential-dependent and independent forms of release. Activation of presynaptic mGluRs depressed the amplitude of stimulus-evoked excitatory postsynaptic currents, but concurrently enhanced the frequency of spontaneous excitatory currents. Moreover, these differential effects on glutamate release were mediated by pharmacologically separable mechanisms. Application of the specific activator of adenylyl cyclase, forskolin, mimicked the effect of mGluR activation on spontaneous, but not evoked release, and inhibition of adenylyl cyclase with 9-tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536) blocked mGluR-mediated enhancement of spontaneous release, but not depression of evoked release. Occlusion studies with calcium channel blockers suggested that the group III mGluRs might depress evoked release through inhibition of both N and P/Q, but not R-type calcium channels. We suggest that the concurrent depression of action potential-evoked, and enhancement of action potential-independent glutamate release operate through discrete second messenger/effector systems at excitatory entorhinal terminals in rat brain. © 2007 IBRO.

The use of presidential executive orders to control the management and administration of the federal government

As long as governmental institutions have existed, efforts have been undertaken to reform them. This research examines a particular strategy, coercive controls, exercised through a particular instrument, executive orders, by a singular reformer, the president of the United States. The presidents studied-- Johnson, Nixon, Ford, Carter, Reagan, Bush, and Clinton--are those whose campaigns for office were characterized to varying degrees as against Washington bureaucracy and for executive reform. Executive order issuance is assessed through an examination of key factors for each president including political party affiliation, levels of political capital, and legislative experience. A classification typology is used to identify the topical dimensions and levels of coerciveness. The portrayal of the federal government is analyzed through examination of public, media, and presidential attention. The results show that executive orders are significant management tools for the president. Executive orders also represent an important component of the transition plans for incoming administrations. The findings indicate that overall, while executive orders have not increased in the aggregate, they are more intrusive and significant. When the factors of political party affiliation, political capital, and legislative experience are examined, it reveals a strong relationship between executive orders and previous executive experience, specifically presidents who served as a state governor prior to winning national election as president. Presidents Carter, Reagan, and Clinton (all former governors) have the highest percent of executive orders focusing on the federal bureaucracy. Additionally, the highest percent of forceful orders were issued by former governors (41.0%) as compared to their presidential counterparts who have not served as governors (19.9%). Secondly, political party affiliation is an important, but not significant, predictor for the use of executive orders. Thirdly, management strategies that provide the president with the greatest level of autonomy--executive orders--redefine the concept of presidential power and autonomous action. Interviews of elite government officials and political observers support the idea that executive orders can provide the president with a successful management strategy, requiring less expenditure of political resources, less risk to political capital, and a way of achieving objectives without depending on an unresponsive Congress. ^

Social-cognitive antecedents of ambidextrous orientation in family-owned startups: The role of family ties, achievement motivation, and internal locus of control

Regulatory Focus Theory predicts that the motivation to self-regulate goal-directed thought and behavior depends on two distinct regulation strategies: a promotion focus based on attaining gains and a prevention focus based on avoiding losses. This study took a social-cognitive approach predicting that regulatory focus has an impact on how family startups (several family related founders) explore "new ideas", exploit "old certainties" and achieve the balance of both (ambidexterity), compared to lone founder startups (only one founder present). It was proposed that the social context of family ties among founders leads them to a prevention focus concerned with avoiding the loss of the socio-emotional benefits of those ties. In order to avoid such a loss, family founders were expected to increase their risk perceptions and thus, explore less than lone founders, who lack such socio-emotional ties. It was also proposed that two commonly used psychological traits in entrepreneurship research —achievement motivation and internal locus of control, predispose entrepreneurs to a promotion focus. Founders with a promotion focus, in turn, were hypothesized to lead startups to more risk-seeking behaviors and to more explorative orientation. The previous argument was used as a springboard to derive hypotheses about ambidexterity (the ability to exploit and explore simultaneously) and survival hazards. Using Regulatory Focus Theory, exploitative orientation, conceptualized as the motivational strength to continue on previous paths of action, was hypothesized to be not significantly different from that of lone founder startups. Taking previous arguments together, lone founder startups were hypothesized to be more ambidextrous than family startups. Finally, ambidexterity and internal locus of control were hypothesized to reduce survival hazards in family startups. The findings suggested that family startups explore less than lone founder startups even after controlling for group effects. Interesting but contradictory findings revealed that internal locus of control have both a positive direct effect and a positive interaction that increases the explorative and ambidextrous orientation gap of family startups over lone founder startups. As expected, ambidexterity and internal locus of control reduced survival hazards on family startups. Implications for practitioners were derived based on a sample of 470 nascent entrepreneurs.

Labor turnover : its causes, consequences, and control strategy in five selected restaurants in the Miami area

The purpose of this study is to identify and analyze the basic causes of food service employee turnover in five selected restaurants in the Miami area. The withdrawal behavior in this study is treated in terms of controllable turnover, for the purpose of management, learning more about what action to take to solve this problem which has eaten into the fabric of the hospitality industry. The aim is to find out from the food service employees and management view of work for the purpose of identifying the variables which cause an employee to voluntarily leave a job. The objective is therefore, to analyze and describe the problem of labor turnover in these selected restaurants. Such description must precede efforts to arrive at solutions to the problem if these efforts are ever to be more than haphazard and superficial. Sigmund Freud once stated: "The true beginning of scientific activity consists in describing phenomena and only then in proceeding to group, classify and correlate them."1 The nature of the study is basically descriptive survey. Data is collected by the use of management questionnaire, food service employee questionnaire and finally employees job description index. The survey consisted of a series of well defined questions with open and closed endings dealing with employee with employee turnover. As Robert Ferber and P. J. Verdoom state in their book titled Research Method in Economics of Business: "Structured questionnaires, by supplying question formulations in very specific terms as well as the different possible answers are easier for the sample members to answer and also serve to reduce the danger of interviewer bias."2 The answers to the prepared questionnaire by sample members were then recorded. The results of the questionnaire responses were then compiled for presentation and analysis. 1 Julian Simon, Basic Research Methods in Social Science. Random House, New York, 1969, p.53. 2 Robert J. Ferber and P.J. Verdoon, Research Methods in Economics and Business, The McMillan Company, 1962, p. 20 9 .

The use of presidential executive orders to control the management and administration of the federal government

As long as governmental institutions have existed, efforts have been undertaken to reform them. This research examines a particular strategy, coercive controls, exercised through a particular instrument, executive orders, by a singular reformer, the president of the United States. The presidents studied- Johnson, Nixon, Ford, Carter, Reagan, Bush, and Clinton-are those whose campaigns for office were characterized to varying degrees as against Washington bureaucracy and for executive reform. Executive order issuance is assessed through an examination of key factors for each president including political party affiliation, levels of political capital, and legislative experience. A classification typology is used to identify the topical dimensions and levels of coerciveness. The portrayal of the federal government is analyzed through examination of public, media, and presidential attention. The results show that executive orders are significant management tools for the president. Executive orders also represent an important component of the transition plans for incoming administrations. The findings indicate that overall, while executive orders have not increased in the aggregate, they are more intrusive and significant. When the factors of political party affiliation, political capital, and legislative experience are examined, it reveals a strong relationship between executive orders and previous executive experience, specifically presidents who served as a state governor prior to winning national election as president. Presidents Carter, Reagan, and Clinton (all former governors) have the highest percent of executive orders focusing on the federal bureaucracy. Additionally, the highest percent of forceful orders were issued by former governors (41.0%) as compared to their presidential counterparts who have not served as governors (19.9%). Secondly, political party affiliation is an important, but not significant, predictor for the use of executive orders. Thirdly, management strategies that provide the president with the greatest level of autonomy-executive orders redefine the concept of presidential power and autonomous action. Interviews of elite government officials and political observers support the idea that executive orders can provide the president with a successful management strategy, requiring less expenditure of political resources, less risk to political capital, and a way of achieving objectives without depending on an unresponsive Congress.

Inclusive pedagogy : from learning to action. Supporting each individual in the context of 'everybody'

Peer reviewed

Inclusive pedagogy : from learning to action. Supporting each individual in the context of 'everybody'

Peer reviewed

Equipment quality control

Mammography equipment must be evaluated to ensure that images will be of acceptable diagnostic quality with lowest radiation dose. Quality Assurance (QA) aims to provide systematic and constant improvement through a feedback mechanism to address the technical, clinical and training aspects. Quality Control (QC), in relation to mammography equipment, comprises a series of tests to determine equipment performance characteristics. The introduction of digital technologies promoted changes in QC tests and protocols and there are some tests that are specific for each manufacturer. Within each country specifi c QC tests should be compliant with regulatory requirements and guidance. Ideally, one mammography practitioner should take overarching responsibility for QC within a service, with all practitioners having responsibility for actual QC testing. All QC results must be documented to facilitate troubleshooting, internal audit and external assessment. Generally speaking, the practitioner’s role includes performing, interpreting and recording the QC tests as well as reporting any out of action limits to their service lead. They must undertake additional continuous professional development to maintain their QC competencies. They are usually supported by technicians and medical physicists; in some countries the latter are mandatory. Technicians and/or medical physicists often perform many of the tests indicated within this chapter. It is important to recognise that this chapter is an attempt to encompass the main tests performed within European countries. Specific tests related to the service that you work within must be familiarised with and adhered too.

The Repellent DEET Potentiates Carbamate Effects via Insect Muscarinic Receptor Interactions: An Alternative Strategy to Control Insect Vector-Borne Diseases.

International audience

Control of grey mould and stem-end rot in strawberry plants growing in a subtropical environment

The effect of different fungicide programs on grey mould (caused by Botrytis cinerea) and stem-end rot (caused by Gnomoniopsis fructicola) affecting strawberry plants (Fragaria ×ananassa cv. Festival) was studied in subtropical Australia over three years. The treatments involved a range of different synthetic multi- and single-site fungicides with different modes of action, a plant-defence promoter, plant extracts (lupin and rhubarb), organic acids, fatty acids, a salt, two strains of Bacillus subtilis, and single strains of B. amyloliquefaciens, Streptomyces lydicus and Trichoderma harzianum. Standard programs based on captan and thiram alternated, and applied with iprodione, fenhexamid, cyprodinil + fludioxonil, and penthiopyrad resulted in 3–4 % of unmarketable fruit compared with 25–38 % in the water-treated controls. There was no difference in the level of disease suppression when five or thirteen applications of single-site fungicides were rotated with the two multi-site fungicides. The incidence of unmarketable fruit was similar to the standard programs using isopyrazam (in 1 year out of 2), or penthiopyrad, fluazinam, chlorothalonil or thiram alone (in 1 year out of 1). The other fungicide programs were generally less effective. There were strong relationships between marketable yield and the incidence of unmarketable fruit over the three years (R2s = 0.82–0.93). A strategy based on thiram and captan applied alternately, with reduced applications of single-site fungicides is recommended and should reduce the chance of resistance to single-site fungicides becoming widespread in populations of the grey mould fungus. Although the program based on thiram alone had a similar incidence of unmarketable fruit as the standard program, repeated weekly applications of thiram are not recommended as they may cause unacceptable residues in the fruit. There were issues with some of the other fungicides due to phytotoxicity, residues, or difficulties with registering new fungicides that are in the same chemical group as currently registered products.

Possible inhibition of hydroxy methyl glutaryl CoA reductase activity by nicotinic acid and ergosterol: as targeting for hypocholesterolemic action.

Objective: Coronary artery diseases including atherosclerosis is considered as commonest problem worldwide. Ergosterols are the main components of vegetable oils and nuts. The objective of this study was to evaluate the potential hypoplipidemic and hypocholesterolemic effects of ergosterol in combination with niacin in rats fed high fat diet (HFD). Methods: Eighty male albino rats were included in this study divided into two main groups: Group I: Normal rats fed standard diet treated with either niacin (8.5 mg /kg b.w) or ergosterol (100 mg/kg b.w) or both. Group II; rats fed HFD treated with either niacin (8.5 mg /kg b.w) or ergosterol (100 mg/kg b.w) or both The feeding and treatment lasted for 8 weeks. Results: A significant elevation in the levels of total cholesterol, triacylglycerol, VLDL-c, LDL-c and atherogenic factor (p<0.001) in rats fed on HFD compared with normal control while HDL-c was significantly reduced in HFD rats compared with control group. Supplementation of diet with niacin or ergosterol or combined exerts improvement in the studied parameters by lowering triacylglycerol, total cholesterol, LDL-c and atherogenic factor and elevate HDL-c near to the value of control. Niacin combined with ergosterol were effective in the reduction of hydroxy methyl glutaryl-CoA reducatase (HMGCoA) compared with control (p<0.001). The combined effect was more potent than individual alone. Conclusion: Utilization of niacin and ergosterol may prevent the hypercholesterolemia and incidence of coronary heart diseases. These functional foods act as nutriceutical as dyslipidemics.