975 resultados para Directed technical change


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As a major European donor, German government development assistance faces a series of challenges. Recent political changes have raised expectations for demonstrable health outcomes as a result of German development assistance; there has been a deepened commitment to collaboration with other bilateral and multilateral donors; and partner countries are increasingly open to new approaches to development. German development assistance also reflects a new ethos of partnership and the shift to programmatic and sector based development approaches. At the same time, its particular organizational structure and administrative framework highlight the extent of structural and systems reforms required of donors by changing development relationships, and the tensions created in responding to these. This paper examines organizational changes within the German Agency for Technical Cooperation (Deutsche Gesellschaft fur Technische Zusammenarbeit) (GTZ), aimed at increasing its Regional, Sectoral, Managerial and Process competence as they affect health and related sectors. These include the decentralization of GTZ, the trend to integration of projects, the increasing focus on policy and health systems reform, increased inter-sectoral collaboration, changes in recruitment and training, new perspectives in planning and evaluation and the introduction of a quality management programme. Copyright (C) 2002 John Wiley Sons, Ltd.

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Cadherin cell adhesion molecules are major determinants of tissue patterning which function in cooperation with the actin cytoskeleton [1-4]. In the context of stable adhesion [1], cadherin/catenin complexes are often envisaged to passively scaffold onto cortical actin filaments. However, cadherins also form dynamic adhesive contacts during wound healing and morphogenesis [2]. Here actin polymerization has been proposed to drive cell surfaces together [5], although F-actin reorganization also occurs as cell contacts mature [6]. The interaction between cadherins and actin is therefore likely to depend on the functional state of adhesion. We sought to analyze the relationship between cadherin homophilic binding and cytoskeletal activity during early cadherin adhesive contacts. Dissecting the specific effect of cadherin ligation alone on actin regulation is difficult in native cell-cell contacts, due to the range of juxtacrine signals that can arise when two cell surfaces adhere [7]. We therefore activated homophilic ligation using a specific functional recombinant protein. We report the first evidence that E-cadherin associates with the Arp2/3 complex actin nucleator and demonstrate that cadherin binding can exert an active, instructive influence on cells to mark sites for actin assembly at the cell surface.

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The aim of the study was to investigate the role of glutamate residue 113 in transmembrane domain 2 of the human noradrenaline transporter in determining cell surface expression and functional activity. This residue is absolutely conserved in all members of the Na+- and Cl--dependent transporter family. Mutations to alanine (hE113A), aspartate (hE113D) and glutamine (hE113Q) were achieved by site-directed mutagenesis and the mutants were expressed in transfected COS-7 or HEK-293 cells. Cell surface expression of IIE113A and hE113D, but not hE113Q, was markedly reduced compared with wild type, and functional noradrenaline uptake was detected only for the hE113Q mutant. The pharmacological properties of the hE113Q mutant showed very little change compared with wild type, except for a decrease in V-max values for noradrenaline and dopamine uptake of 2-3-fold. However, the hE113D mutant showed very marked changes in its properties, compared with wild type, with 82-260-fold decreases in the affinities of the substrates, noradrenaline, dopamine and MPP+, and increased Na+ affinity for stimulation of nisoxetine binding. The results of the study show that the size and not the charge of the 113 glutamate residue of the noradrenaline transporter seems to be the most critical factor for maintenance of transporter function and surface expression.

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Highly conserved motifs in the monoamine transporters, e.g. the human norepinephrine transporter (hNET) GXXXRXG motif which was the focus of the present study, are likely to be important structural features in determining function. This motif was investigated by mutating the glycines to glutamate (causing loss of function) and alanine, and the arginine to glycine. The effects of hG117A, hR121G and hG123A mutations on function were examined in COS-7 cells and compared to hNET. Substrate K-m values were decreased for hG117A and hG123A, and their K values for inhibition of [3 H]nisoxetine binding were decreased 3-4-fold and 4-6-fold, respectively. Transporter turnover was reduced to 65% of hNET for hG117A and hR121G and to 28% for hG123A, suggesting that substrate translocation is impaired. K values of nisoxetine and desipramine for inhibition of [H-3]norepinephrine uptake were increased by 5-fold for hG117A, with no change for cocaine. The K-i value of cocaine was increased by 3-fold for hG123A, with no change for nisoxetine and desipramine. However, there were no effects of the mutations on the K-d of [H-3]nisoxetine binding or K-i values of desipramine or cocaine for inhibition of [H-3]nisoxetine binding. Hence, glycine residues of the GXXXRXG motif are important determinants of NET expression and function, while the arginine residue does not have a major role. This study also showed that antidepressants and psychostimulants have different NET binding sites and provided the first evidence that different sites on the NET are involved in the binding of inhibitors and their competitive inhibition of substrate uptake. (C) 2002 Elsevier Science B.V. All rights reserved.

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This paper examines the proposition that the traditional archetype of the professional partnership is said to have changed into a more 'business-like' entity, the managed professional business. It broadens the restricted case sample base on which much of the evidence has been adduced, by developing a survey questionnaire through which 197 large British law firms were sampled. Change, consistent with the notion of a more commercially oriented and consciously managed organization, is concentrated in the market-facing area of the firm but coexists with areas of continuity in the governance of the firm and its strategic management. The findings reveal a more managerial form of organization in which the core elements of the traditional form of professional organization have not been transformed. These results contest the assertion of either transformational or sedimented change found in other, case-based research and suggest that archetype change needs theoretically to be distinguished from the general phenomenon of greater managerialism within the professional service firm.

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The purpose of this study was to quantify the sagittal angular displacement of the head (cranio-cervical flexion) for the five incremental stages of the cranio-cervical flexion test (CCFT). Range of cranio-cervical flexion during the CCFT was measured using a digital imaging method in 20 healthy volunteer subjects. The intra- and inter-rater reliability of the digital imaging technique for the assessment of this movement were also examined. The results of this study demonstrated a linear relationship between the incremental pressure targets of the CCFT and the percentages of full range cranio-cervical flexion range of motion (ROM) measured in the supine lying position of the test using a digital imaging technique. A mean of 22.9% full range cranio-cervical flexion was used to reach the first pressure target of the CCFT followed by linear increments up to 76.6% for the last stage of the test. An increasing amount of cranio-cervical flexion ROM was used to achieve the five successive stages of the CCFT reflecting an increasing contractile demand on the deep cervical flexor muscles. Excellent inter-rater (ICC = 0.994) and intra-rater reliability (ICC = 0.988-0.998) were demonstrated for the angular measurements using this digital imaging technique. (C) 2003 Elsevier Science Ltd. All rights reserved.

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Although ATM, the protein defective in ataxia-telangiectasia (A-T), is activated primarily by radiation, there is also evidence that expression of the protein can be regulated by both radiation and growth factors. Computer analysis of the ATM promoter proximal 700-bp sequence reveals a number of potentially important cis-regulatory sequences. Using nucleotide substitutions to delete putative functional elements in the promoter of ATM, we examined the importance of some of these sites for both the basal and the radiation-induced activity of the promoter. In lymphoblastoid cells, most of the mutations in transcription factor consensus sequences [Sp1(1), Sp1(2), Cre, Ets, Xre, gammaIre(2), a modified AP1 site (Fse), and GCF] reduced basal activity to various extents, whereas others [gammaIre(1), NF1, Myb] left basal activity unaffected. In human skin fibroblasts, results were generally the same, but the basal activity varied up to 8-fold in these and other cell lines. Radiation activated the promoter approximately 2.5-fold in serum-starved lymphoblastoid cells, reaching a maximum by 3 hr, and all mutated elements equally blocked this activation. Reduction in Sp1 and AP1 DNA binding activity by serum starvation was rapidly reversed by exposure of cells to radiation. This reduction was not evident in A-T cells, and the response to radiation was less marked. Data provided for interaction between ATM and Sp1 by protein binding and co-immunoprecipitation could explain the altered regulation of Sp1 in A-T cells. The data described here provide additional evidence that basal and radiation-induced regulation of the ATM promoter is under multifactorial control. (C) 2003 Wiley-Liss, Inc.

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The People in Pain course was set up as a joint initiative of the Departments of Occupational Therapy and Physiotherapy within the School of Health and Rehabilitation Sciences at The University of Queensland. It was instigated in response to the publication of Pain Curricula for Occupational Therapy and Physiotherapy by the International Association for the Study of Pain (IASP) in 1994 (1). The first year it was offered, the "People in Pain" course comprised 14 h of lecture content. It was then expanded to encompass 28 h of lectures and seminar involvement. OBJECTIVES: To evaluate the impact of participation in a university pain course that meets the IASP pain curricula guidelines to increase health professional students' knowledge about pain. METHODS: Students who participated in the People in Pain course over the first three years were invited to complete the Revised Pain Knowledge and Attitudes Questionnaire (R-PKAQ) pre- and postcourse. Data obtained from 22 students in the short course formed a pilot project, and data from 22 students in the longer version of the course were used in the present study. RESULTS: Examination of the correlation matrix indicated substantial correlations between all R-PKAQ subscales except physiological basis of pain and pharmacological management of pain. In both the pilot project during the first year of the course and the expanded course in the following two years, significant improvement was found in the students' knowledge on five of the six subscales of the R-PKAQ: physiological basis of pain, psychological factors of pain perception, assessment and measurement of pain, cognitive-behavioural methods of pain relief, and pharmacological management of pain. Improvements in the developmental aspects of pain perception subscale failed to reach significance. CONCLUSIONS: An integrated pain course developed according to the pain curriculum guidelines developed by the IASP resulted in increased student knowledge regardless of the length of the program attended.

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Three studies support the vicarious dissonance hypothesis that individuals change their attitudes when witnessing members of important groups engage in inconsistent behavior. Study 1, in which participants observed an actor in an induced-compliance paradigm, documented that students who identified with their college supported an issue more after hearing an ingroup member make a counterattitudinal speech in favor of that issue. In Study 2, vicarious dissonance occurred even when participants did not hear a speech, and attitude change was highest when the speaker was known to disagree with the issue. Study 3 showed that speaker choice and aversive consequences moderated vicarious dissonance, and demonstrated that vicarious discomfort-the discomfort observers imagine feeling if in an actor's place-was attenuated after participants expressed their revised attitudes.

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The impacts of climate change in the potential distribution and relative abundance of a C3 shrubby vine, Cryptostegia grandiflora, were investigated using the CLIMEX modelling package. Based upon its current naturalised distribution, C. grandiflora appears to occupy only a small fraction of its potential distribution in Australia under current climatic conditions; mostly in apparently sub-optimal habitat. The potential distribution of C. grandiflora is sensitive towards changes in climate and atmospheric chemistry in the expected range of this century, particularly those that result in increased temperature and water use efficiency. Climate change is likely to increase the potential distribution and abundance of the plant, further increasing the area at risk of invasion, and threatening the viability of current control strategies markedly. By identifying areas at risk of invasion, and vulnerabilities of control strategies, this analysis demonstrates the utility of climate models for providing information suitable to help formulate large-scale, long-term strategic plans for controlling biotic invasions. The effects of climate change upon the potential distribution of C. grandiflora are sufficiently great that strategic control plans for biotic invasions should routinely include their consideration. Whilst the effect of climate change upon the efficacy of introduced biological control agents remain unknown, their possible effect in the potential distribution of C. grandiflora will likely depend not only upon their effects on the population dynamics of C. grandiflora, but also on the gradient of climatic suitability adjacent to each segment of the range boundary.

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This paper describes a process-based metapopulation dynamics and phenology model of prickly acacia, Acacia nilotica, an invasive alien species in Australia. The model, SPAnDX, describes the interactions between riparian and upland sub-populations of A. nilotica within livestock paddocks, including the effects of extrinsic factors such as temperature, soil moisture availability and atmospheric concentrations of carbon dioxide. The model includes the effects of management events such as changing the livestock species or stocking rate, applying fire, and herbicide application. The predicted population behaviour of A. nilotica was sensitive to climate. Using 35 years daily weather datasets for five representative sites spanning the range of conditions that A. nilotica is found in Australia, the model predicted biomass levels that closely accord with expected values at each site. SPAnDX can be used as a decision-support tool in integrated weed management, and to explore the sensitivity of cultural management practices to climate change throughout the range of A. nilotica. The cohort-based DYMEX modelling package used to build and run SPAnDX provided several advantages over more traditional population modelling approaches (e.g. an appropriate specific formalism (discrete time, cohort-based, process-oriented), user-friendly graphical environment, extensible library of reusable components, and useful and flexible input/output support framework). (C) 2003 Published by Elsevier Science B.V.