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Ativação supraespinal da via das quinureninas contribui para a manutenção da dor neuropática / Supraspinal kynurenine pathway contributes to the maintenance of neuropathic painReis, Dênis Augusto Santana 03 February 2015 (has links)
Introdução: Um fator que pode contribuir para o desenvolvimento da dor neuropática é a modulação negativa da via descendente da dor pelo aumento da degradação do triptofano pela ativação da enzima indoleamina 2,3-dioxigenase 1 (IDO1) ou a ativação da via descendente facilitatória da dor por um agonista glutamatérgicos produzido pela enzima quinurenina 3 monoxigenase (KMO). Objetivo: Foi avaliar a participação das enzimas IDO1 e a KMO presente na substância cinzenta periaquedutal (PAG) e no bulbo rostral ventromedial (RVM) no desenvolvimento da dor neuropática em camundongos induzida pelo modelo SNI. Metodologia: A indução da neuropatia experimental foi realizada de acordo com (Bourquin et al., 2006). A expressão da IDO1 e KMO foi realizada pela técnica de Western blotting. A administração de drogas foi realizada por via oral, intraperitoneal, intratecal e intracerebroventricular (i.c.v.). Resultados: Foi observado o aumento da expressão da enzima IDO1 no RVM (7 dias) e PAG (3, 7, 14 e 21 dias) após SNI. A microinjeção de Norharmane no espaço i.c.v. reduziu a hipersensibilidade mecânica no 7, 14 e 21 dias após SNI. Corroborando com esses achados, animais deficientes para a enzima IDO1 submetidos a SNI não desenvolvem a hipersensibilidade mecânica. Além disso, a expressão da enzima KMO aumenta significativamente no 7 e 14 dias no RVM e 7 dias na PAG após SNI. Por conseguinte, a administração oral de JM6, pró-droga de liberação lenta do Ro61-8048, ou Ro61-8048 (inibidor da KMO) no espaço i.c.v. reduziu significativamente a hipersensibilidade mecânica nos dias 7, 14 ou 21 após SNI. Sabendo que a expressão da enzima IDO1 é modulada pela citocina IFN-, verificamos que os animais deficientes para a citocina IFN- apresentam hipersensibilidade mecânica reduzida. Ainda, os animais IFN- KO possuem expressão reduzida da IDO1 no RVM 7 dias e na PAG 14 dias após a SNI. Em adição, a microinjeção de doses crescentes de IFN- no espaço i.c.v. induz uma hipernocicepção mecânica em camundongos naives. Constatamos também que animais CD4+ KO, mas não os animais CD8+ KO apresentam reduzida expressão da enzima IDO1 no RVM e na PAG e consequentemente menor hipersensibilidade mecânica após SNI. A microinjeção dos metabolitos da via das quinureninas, no espaço i.c.v. de camundongos causou hipersensibilidade mecânica, sendo o QUIN o mais potente. Sugerimos que a ativação da via das quinureninas seja dependente da ativação do receptor NMDA, visto que o pré-tratamento local com o MK801 (antagonista seletivos dos receptores NMDA) reverte os efeitos nociceptivos induzidos pelos metabólitos. Além disso, o efeito nociceptivo induzido por QUIN depende ativação da via descendente facilitatória. Constatamos que os animais neuropáticos exibem um comportamento do tipo depressivo e esse comportamento não é observado em animais IFN- KO e CD4KO. Por último, avaliamos a participação da via das quinureninas no desenvolvimento do comportamento depressivo associado à SNI e constatamos que esse comportamento depende da ativação das enzimas IDO1 e KMO. Conclusão: Os resultados sugerem que as enzimas IDO1 e KMO, localizadas em regiões supraespinais desempenham um importante papel no desenvolvimento da dor neuropática, assim como da comorbidade depressão. Além disso, a expressão da IDO1 é dependente da sinalização via citocina IFN- e células CD4+. O mecanismo responsável pelo desenvolvimento da hipersensibilidade neuropática deve-se tanto a redução dos níveis de triptofano/5-HT, diminuição da eficiência da via descendente inibitória, quanto ao aumento dos níveis de QUIN, que ativa a via descendente facilitatória da dor. / Introduction: One factor that may contribute to the development of neuropathic pain is the negative modulation of the descending pain pathway by increased degradation of the activation of tryptophan by enzyme indoleamine 2,3-dioxygenase1 (IDO1) or activation of the descending facilitatory pain pathway for a glutamate agonist produced by the enzyme kynurenine 3 monooxygenase (KMO). Aim: We evaluate the role of IDO1 and KMO in the periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM) in the development of neuropathic pain in mice induced by SNI model. Methods: Induction of experimental neuropathy was performed according to (Bourquin et al. 2006). The expression of IDO1 and KMO was carried out by Western blotting technique. The drug administration was performed orally, intraperitoneally and intracerebroventricularly (i.c.v) Results. We observed increased IDO1 expression in the RVM (7 days) and PAG (3, 7, 14 and 21 days) after SNI. The microinjection Norharmane in i.c.v. space reduced mechanical hypersensitivity in the 7, 14 and 21 days after SNI. Corroborating these findings, mice deficient for the enzyme IDO1 undergoing SNI did not develop mechanical hypersensitivity. Furthermore, the KMO expression was significantly increased in the 7 and 14 days in the RVM and 7 days in PAG after SNI. Therefore, oral administration of JM6, prodrug slow release from Ro61-8048 or Ro61-8048 (KMO inhibitors) within i.c.v. significantly reduced the mechanical hypersensitivity at day 7, 14 or 21 after SNI. Knowing that the expression of IDO1 enzyme is modulated by IFN- cytokine, it was found that animals deficient for IFN- cytokine have reduced mechanical hypersensitivity. Moreover, IFN- ko animals have reduced expression of IDO1 RVM 7 days and 14 days after SNI in the PAG. In addition, microinjection of increasing doses of IFN- in i.c.v. induced mechanical hyperalgesia. We also found that CD4 + KO animals, but not CD8 + KO animals showed reduced expression of the enzyme IDO1 RVM and PAG and consequently lower mechanical hypersensitivity after SNI. The microinjection of the main metabolites of kynurenine pathway into the i.c.v. spaces induced mechanical hypersensitivity, QUIN being the most potent. We suggest that the activation of the kynurenine pathway was dependent of NMDA receptor activation, whereas the spot pre-treatment with MK801 (selective NMDA receptor antagonist) reverses the effects induced by noxious metabolites. After that, the microinjection into i.c.v. spaces of MK801 reduced mechanical hypersensitivity after SNI. Furthermore, nociceptive effect induced by QUIN depends activation of the descending facilitatory. We found that the neuropathic animals exhibit depressive-like behavior and this behavior is not observed in IFN- KO and CD4KO mice. Finally, we evaluate the participation of kynurenine pathway in the development of depressive-like behavior associated with SNI and found that this behavior depends on the activation of IDO1 and KMO Conclusion: These results suggest that IDO1 and KMO enzyme, located in supraspinal regions play a role in the development of neuropathic pain as well as comorbidity depression. Furthermore, the expression of IDO1 are dependent on signaling via cytokine IFN- and CD4+ cells. The mechanism responsible for the development of neuropathic hypersensitivity is due to both reduced levels of tryptophan/5-HT decrease the descending inhibitory pain pathway efficiency, as the increased levels of QUIN, which activates the descending facilitatory pain pathway.
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Ativação supraespinal da via das quinureninas contribui para a manutenção da dor neuropática / Supraspinal kynurenine pathway contributes to the maintenance of neuropathic painDênis Augusto Santana Reis 03 February 2015 (has links)
Introdução: Um fator que pode contribuir para o desenvolvimento da dor neuropática é a modulação negativa da via descendente da dor pelo aumento da degradação do triptofano pela ativação da enzima indoleamina 2,3-dioxigenase 1 (IDO1) ou a ativação da via descendente facilitatória da dor por um agonista glutamatérgicos produzido pela enzima quinurenina 3 monoxigenase (KMO). Objetivo: Foi avaliar a participação das enzimas IDO1 e a KMO presente na substância cinzenta periaquedutal (PAG) e no bulbo rostral ventromedial (RVM) no desenvolvimento da dor neuropática em camundongos induzida pelo modelo SNI. Metodologia: A indução da neuropatia experimental foi realizada de acordo com (Bourquin et al., 2006). A expressão da IDO1 e KMO foi realizada pela técnica de Western blotting. A administração de drogas foi realizada por via oral, intraperitoneal, intratecal e intracerebroventricular (i.c.v.). Resultados: Foi observado o aumento da expressão da enzima IDO1 no RVM (7 dias) e PAG (3, 7, 14 e 21 dias) após SNI. A microinjeção de Norharmane no espaço i.c.v. reduziu a hipersensibilidade mecânica no 7, 14 e 21 dias após SNI. Corroborando com esses achados, animais deficientes para a enzima IDO1 submetidos a SNI não desenvolvem a hipersensibilidade mecânica. Além disso, a expressão da enzima KMO aumenta significativamente no 7 e 14 dias no RVM e 7 dias na PAG após SNI. Por conseguinte, a administração oral de JM6, pró-droga de liberação lenta do Ro61-8048, ou Ro61-8048 (inibidor da KMO) no espaço i.c.v. reduziu significativamente a hipersensibilidade mecânica nos dias 7, 14 ou 21 após SNI. Sabendo que a expressão da enzima IDO1 é modulada pela citocina IFN-, verificamos que os animais deficientes para a citocina IFN- apresentam hipersensibilidade mecânica reduzida. Ainda, os animais IFN- KO possuem expressão reduzida da IDO1 no RVM 7 dias e na PAG 14 dias após a SNI. Em adição, a microinjeção de doses crescentes de IFN- no espaço i.c.v. induz uma hipernocicepção mecânica em camundongos naives. Constatamos também que animais CD4+ KO, mas não os animais CD8+ KO apresentam reduzida expressão da enzima IDO1 no RVM e na PAG e consequentemente menor hipersensibilidade mecânica após SNI. A microinjeção dos metabolitos da via das quinureninas, no espaço i.c.v. de camundongos causou hipersensibilidade mecânica, sendo o QUIN o mais potente. Sugerimos que a ativação da via das quinureninas seja dependente da ativação do receptor NMDA, visto que o pré-tratamento local com o MK801 (antagonista seletivos dos receptores NMDA) reverte os efeitos nociceptivos induzidos pelos metabólitos. Além disso, o efeito nociceptivo induzido por QUIN depende ativação da via descendente facilitatória. Constatamos que os animais neuropáticos exibem um comportamento do tipo depressivo e esse comportamento não é observado em animais IFN- KO e CD4KO. Por último, avaliamos a participação da via das quinureninas no desenvolvimento do comportamento depressivo associado à SNI e constatamos que esse comportamento depende da ativação das enzimas IDO1 e KMO. Conclusão: Os resultados sugerem que as enzimas IDO1 e KMO, localizadas em regiões supraespinais desempenham um importante papel no desenvolvimento da dor neuropática, assim como da comorbidade depressão. Além disso, a expressão da IDO1 é dependente da sinalização via citocina IFN- e células CD4+. O mecanismo responsável pelo desenvolvimento da hipersensibilidade neuropática deve-se tanto a redução dos níveis de triptofano/5-HT, diminuição da eficiência da via descendente inibitória, quanto ao aumento dos níveis de QUIN, que ativa a via descendente facilitatória da dor. / Introduction: One factor that may contribute to the development of neuropathic pain is the negative modulation of the descending pain pathway by increased degradation of the activation of tryptophan by enzyme indoleamine 2,3-dioxygenase1 (IDO1) or activation of the descending facilitatory pain pathway for a glutamate agonist produced by the enzyme kynurenine 3 monooxygenase (KMO). Aim: We evaluate the role of IDO1 and KMO in the periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM) in the development of neuropathic pain in mice induced by SNI model. Methods: Induction of experimental neuropathy was performed according to (Bourquin et al. 2006). The expression of IDO1 and KMO was carried out by Western blotting technique. The drug administration was performed orally, intraperitoneally and intracerebroventricularly (i.c.v) Results. We observed increased IDO1 expression in the RVM (7 days) and PAG (3, 7, 14 and 21 days) after SNI. The microinjection Norharmane in i.c.v. space reduced mechanical hypersensitivity in the 7, 14 and 21 days after SNI. Corroborating these findings, mice deficient for the enzyme IDO1 undergoing SNI did not develop mechanical hypersensitivity. Furthermore, the KMO expression was significantly increased in the 7 and 14 days in the RVM and 7 days in PAG after SNI. Therefore, oral administration of JM6, prodrug slow release from Ro61-8048 or Ro61-8048 (KMO inhibitors) within i.c.v. significantly reduced the mechanical hypersensitivity at day 7, 14 or 21 after SNI. Knowing that the expression of IDO1 enzyme is modulated by IFN- cytokine, it was found that animals deficient for IFN- cytokine have reduced mechanical hypersensitivity. Moreover, IFN- ko animals have reduced expression of IDO1 RVM 7 days and 14 days after SNI in the PAG. In addition, microinjection of increasing doses of IFN- in i.c.v. induced mechanical hyperalgesia. We also found that CD4 + KO animals, but not CD8 + KO animals showed reduced expression of the enzyme IDO1 RVM and PAG and consequently lower mechanical hypersensitivity after SNI. The microinjection of the main metabolites of kynurenine pathway into the i.c.v. spaces induced mechanical hypersensitivity, QUIN being the most potent. We suggest that the activation of the kynurenine pathway was dependent of NMDA receptor activation, whereas the spot pre-treatment with MK801 (selective NMDA receptor antagonist) reverses the effects induced by noxious metabolites. After that, the microinjection into i.c.v. spaces of MK801 reduced mechanical hypersensitivity after SNI. Furthermore, nociceptive effect induced by QUIN depends activation of the descending facilitatory. We found that the neuropathic animals exhibit depressive-like behavior and this behavior is not observed in IFN- KO and CD4KO mice. Finally, we evaluate the participation of kynurenine pathway in the development of depressive-like behavior associated with SNI and found that this behavior depends on the activation of IDO1 and KMO Conclusion: These results suggest that IDO1 and KMO enzyme, located in supraspinal regions play a role in the development of neuropathic pain as well as comorbidity depression. Furthermore, the expression of IDO1 are dependent on signaling via cytokine IFN- and CD4+ cells. The mechanism responsible for the development of neuropathic hypersensitivity is due to both reduced levels of tryptophan/5-HT decrease the descending inhibitory pain pathway efficiency, as the increased levels of QUIN, which activates the descending facilitatory pain pathway.
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Novel screening techniques for the discovery of human KMO inhibitorsWilson, Kris January 2014 (has links)
Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan degradation. KMO is emerging as an increasingly important target for drug development. The enzyme is implicated in the development and progression of several neurodegenerative disorders, in the regulation of the immune response and in sterile systemic inflammation. Production of recombinant human enzyme is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Although several in vitro KMO assay techniques have been reported in the literature these methods are typically insensitive or require purified protein for use in high-throughput screening assays of human KMO enzyme. The first report of bacterial expression of soluble active human KMO enzyme is described here. Fusion protein tags were used to optimise soluble expression and enable characterisation and partial purification of the active protein constructs. Functional enzyme was used to develop several novel high-throughput drug screening techniques for the discovery of inhibitors specifically targeting human KMO. These screening techniques were fully characterised and validated using known KMO inhibitors from the patent literature. One of the novel KMO assay techniques was implemented for compound screening and several hit compounds were identified, validated and their in vitro DMPK characteristics determined. In addition to assay development, KMO was characterised at the cellular level when overexpressed in HEK293 cells. These experiments indicated that KMO overexpressing cells undergo bidirectional adaptation via alteration of kynurenine pathway homeostasis. As a result, these cells are protected from cytotoxicity mediated by 3-hydroxykynurenine (3-HK), the toxic product of KMO catalysis. The development of novel high throughput screening techniques targeting KMO has enabled screening of potential new inhibitors specifically targeting the human enzyme. Implementation of these screening assays will allow accelerated and improved discovery and development of novel KMO inhibitors for the potential treatment of numerous disease states.
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HAPPINESS INDEXTHE CONSTRUCTION AND ANALYSISERIC, AIDOO, SAIJING, ZHENG January 2010 (has links)
This study aims to investigate the important indicators that contribute to happiness among Beijing residence. The residents of Beijing were taken as the target population for the survey. A questionnaire was used as the main statistical instrument to collect the data from the residents in Beijing. In so doing the investigation employs Factor analyses and chi-square analyses as the main statistical tools used for the analyses in this research. The study found that Beijing residents gained greater happiness in the family, interpersonal relationships, and health status. The analysis also shows that generally, the residence of Beijing feels happier and also in terms of gender basis, females in Beijing feel happier as compare to their male counterpart. It will find that gender, age and education are statistically significant when dealing with happiness.
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A comparison of the characteristics of internationalising SMEs in South Africa and the BRIC countries / Lamprecht J.L.D.Lamprecht, Jacobus Lodewicus du Plessis January 2011 (has links)
SMEs are important for a country's economy, since they provide benefits such as entrepreneurship, employment, exports and productivity to an economy. An economy that shows substantial growth is usually characterised by a strong and growing SME sector. South African SMEs need to grow to create jobs and benefit the South African economy. One way that SMEs can become strong and grow is through internationalisation. Firms are internationalising faster than ever before (because of advances in telecommunications and transportation) and internationalisation theories that can provide practical guidance to firms are more important today than in the past.
The motivation of the study was to identify the areas that the South African government can develop in order to transform the economy into an emerging economy that can be on par with the BRIC countries. SMEs make up a large part of the BRICS economies and they grow through exports. In order to be on par with the BRIC countries, it is necessary to compare South African exporting and non–exporting SMEs with those in the BRIC countries. This will help to identify areas where South African SMEs' competitiveness can improve, especially in South–South trade. The competitiveness of SMEs involved in exporting also tends to improve. Therefore, if SMEs' competitiveness improves, it may be less risky for them to internationalise, which can lead to them being able to export more successfully, grow as a result of exporting and so contribute to employment.
The primary objective of the study was to make a comparison between the characteristics of internationalising SMEs in South Africa and the BRICS countries. Data was obtained from the World Bank Enterprise surveys to conduct an empirical analysis on firms in the BRICS countries. The empirical analysis provided descriptive statistics on internationalising firms and SMEs in the BRICS countries. The descriptive statistics was used to make a comparison between the characteristics of internationalising SMEs in the BRICS countries (primary objective). South Africa has the highest percentage of
exporting SMEs, followed by India, Brazil, Russia and China. China had the most exporting SMEs with an internationally recognised certification. The top managers of Chinese exporting SMEs are higher educated than those in India and South Africa. SMEs in Russia internationalise at by far the youngest age and thus are likely to follow the rapid international theories. South African SMEs had the highest average age, meaning that SMEs first are established in the domestic market before they internationalise through exports.
Internationalisation has become an important strategy for firms that want to achieve further growth, but it is also very tough to survive in the international market. An interesting finding of this study was that the two obstacles South Africa had in the top 5 namely, crime, theft and disorder, and electricity were not a top 5 obstacle for any of the other BRIC countries.
Another objective of the study was to empirically determine the characteristics of internationalising SMEs in South Africa. SMEs in South Africa are more likely to internationalise through exports if they are, amongst others, older (longer established in the domestic market), have a larger market share in the South African domestic market, have a top manager with experience and a higher education level (some university training minimum) and have less competitors in the South African domestic market.
The comparison between the characteristics of internationalising SMEs of the BRICS countries provided several lessons for the South African government and exporting SMEs. The areas or aspects that the South African government need to develop in order to transform the economy into an emerging economy that can compete with the BRIC countries, include assisting SMEs in exporting at an earlier age, improving the education levels of top managers in SMEs, increasing the national market share of SMEs and lessening, or even eliminating, obstacles like crime, theft and disorder as well as electricity. These aspects, together with the characteristics of internationalising SMEs in South Africa, are vital to improve SME competitiveness. Therefore, if SMEs' competitiveness improves, then it may be less risky for them to internationalise, which
can lead to them being able to export more successfully, grow as a result of exporting and so contribute to employment. / Thesis (M.Com. (International Trade))--North-West University, Potchefstroom Campus, 2012.
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A comparison of the characteristics of internationalising SMEs in South Africa and the BRIC countries / Lamprecht J.L.D.Lamprecht, Jacobus Lodewicus du Plessis January 2011 (has links)
SMEs are important for a country's economy, since they provide benefits such as entrepreneurship, employment, exports and productivity to an economy. An economy that shows substantial growth is usually characterised by a strong and growing SME sector. South African SMEs need to grow to create jobs and benefit the South African economy. One way that SMEs can become strong and grow is through internationalisation. Firms are internationalising faster than ever before (because of advances in telecommunications and transportation) and internationalisation theories that can provide practical guidance to firms are more important today than in the past.
The motivation of the study was to identify the areas that the South African government can develop in order to transform the economy into an emerging economy that can be on par with the BRIC countries. SMEs make up a large part of the BRICS economies and they grow through exports. In order to be on par with the BRIC countries, it is necessary to compare South African exporting and non–exporting SMEs with those in the BRIC countries. This will help to identify areas where South African SMEs' competitiveness can improve, especially in South–South trade. The competitiveness of SMEs involved in exporting also tends to improve. Therefore, if SMEs' competitiveness improves, it may be less risky for them to internationalise, which can lead to them being able to export more successfully, grow as a result of exporting and so contribute to employment.
The primary objective of the study was to make a comparison between the characteristics of internationalising SMEs in South Africa and the BRICS countries. Data was obtained from the World Bank Enterprise surveys to conduct an empirical analysis on firms in the BRICS countries. The empirical analysis provided descriptive statistics on internationalising firms and SMEs in the BRICS countries. The descriptive statistics was used to make a comparison between the characteristics of internationalising SMEs in the BRICS countries (primary objective). South Africa has the highest percentage of
exporting SMEs, followed by India, Brazil, Russia and China. China had the most exporting SMEs with an internationally recognised certification. The top managers of Chinese exporting SMEs are higher educated than those in India and South Africa. SMEs in Russia internationalise at by far the youngest age and thus are likely to follow the rapid international theories. South African SMEs had the highest average age, meaning that SMEs first are established in the domestic market before they internationalise through exports.
Internationalisation has become an important strategy for firms that want to achieve further growth, but it is also very tough to survive in the international market. An interesting finding of this study was that the two obstacles South Africa had in the top 5 namely, crime, theft and disorder, and electricity were not a top 5 obstacle for any of the other BRIC countries.
Another objective of the study was to empirically determine the characteristics of internationalising SMEs in South Africa. SMEs in South Africa are more likely to internationalise through exports if they are, amongst others, older (longer established in the domestic market), have a larger market share in the South African domestic market, have a top manager with experience and a higher education level (some university training minimum) and have less competitors in the South African domestic market.
The comparison between the characteristics of internationalising SMEs of the BRICS countries provided several lessons for the South African government and exporting SMEs. The areas or aspects that the South African government need to develop in order to transform the economy into an emerging economy that can compete with the BRIC countries, include assisting SMEs in exporting at an earlier age, improving the education levels of top managers in SMEs, increasing the national market share of SMEs and lessening, or even eliminating, obstacles like crime, theft and disorder as well as electricity. These aspects, together with the characteristics of internationalising SMEs in South Africa, are vital to improve SME competitiveness. Therefore, if SMEs' competitiveness improves, then it may be less risky for them to internationalise, which
can lead to them being able to export more successfully, grow as a result of exporting and so contribute to employment. / Thesis (M.Com. (International Trade))--North-West University, Potchefstroom Campus, 2012.
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Trade finance as a barrier to SME internationalisation: special reference to African trade with China / Y. van HeerdenVan Heerden, Yvette January 2010 (has links)
The importance of small and medium-sized enterprises (SMEs) in the economy should not be overlooked. The main function of SMEs is to contribute to the economic activities in a country, through the provision of goods and services to the public or other firms. These goods and services could be traded internationally, thus increasing a country?s export performance. It is important for economic growth that SMEs grow within their respective economies. One way that SMEs can achieve growth is through internationalisation. Firms are internationalising faster than ever before (because of advances in telecommunications and transportation) and internationalisation theories that can provide practical guidance to firms are more important today than in the past.
A firm?s ability to internationalise no longer only depends on the quality of the product, the delivery terms and competitive prices. Internationalisation increasingly depends on the ability and willingness of financial institutions to grant credit. Obtaining trade finance has become a major hindrance to SME internationalisation, especially in Africa. By overcoming the difficulties in obtaining trade finance, African SMEs will be able to expand into foreign markets.
The purpose of this study is to determine how African SMEs can overcome trade finance barriers to internationalisation. SMEs can do so by mitigating the risks involved in every international transaction and by becoming ?trade finance ready?.
A trade finance facility that is well suited for African SMEs (because it revolves around identifying and mitigating the risks involved with their international transactions) is structured trade and commodity finance. In trading with China, African SMEs can obtain structured trade and commodity finance from a specialist financial institution that focuses on the Chinese market (which is the focus of this study). China Construction Bank (Johannesburg branch), through their association with Rand-Asia Trade Finance, provides structured trade and commodity finance to African SMEs. The key to receiving structured trade and commodity finance is that these SMEs, together with China Construction Bank (Jhb) and Rand-Asia Trade Finance have to mitigate the risks involved with their international transactions so that the SMEs can become ?trade finance ready?. / Thesis (M.Com. (International Commerce))--North-West University, Potchefstroom Campus, 2011.
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Trade finance as a barrier to SME internationalisation: special reference to African trade with China / Y. van HeerdenVan Heerden, Yvette January 2010 (has links)
The importance of small and medium-sized enterprises (SMEs) in the economy should not be overlooked. The main function of SMEs is to contribute to the economic activities in a country, through the provision of goods and services to the public or other firms. These goods and services could be traded internationally, thus increasing a country?s export performance. It is important for economic growth that SMEs grow within their respective economies. One way that SMEs can achieve growth is through internationalisation. Firms are internationalising faster than ever before (because of advances in telecommunications and transportation) and internationalisation theories that can provide practical guidance to firms are more important today than in the past.
A firm?s ability to internationalise no longer only depends on the quality of the product, the delivery terms and competitive prices. Internationalisation increasingly depends on the ability and willingness of financial institutions to grant credit. Obtaining trade finance has become a major hindrance to SME internationalisation, especially in Africa. By overcoming the difficulties in obtaining trade finance, African SMEs will be able to expand into foreign markets.
The purpose of this study is to determine how African SMEs can overcome trade finance barriers to internationalisation. SMEs can do so by mitigating the risks involved in every international transaction and by becoming ?trade finance ready?.
A trade finance facility that is well suited for African SMEs (because it revolves around identifying and mitigating the risks involved with their international transactions) is structured trade and commodity finance. In trading with China, African SMEs can obtain structured trade and commodity finance from a specialist financial institution that focuses on the Chinese market (which is the focus of this study). China Construction Bank (Johannesburg branch), through their association with Rand-Asia Trade Finance, provides structured trade and commodity finance to African SMEs. The key to receiving structured trade and commodity finance is that these SMEs, together with China Construction Bank (Jhb) and Rand-Asia Trade Finance have to mitigate the risks involved with their international transactions so that the SMEs can become ?trade finance ready?. / Thesis (M.Com. (International Commerce))--North-West University, Potchefstroom Campus, 2011.
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Säker och tidseffektiv förflyttning av betongelement / Safe and time-efficient transport of prefabricated concrete elementsAndersson, Isac, Ström, Erik January 2020 (has links)
Vid konstruktion med betong har prefabricerade betongelement blivit allt mer frekvent förekommande. I samband med detta blir moment som förflyttning av betongelement ett problem under tillverkning, på grund av dess storlek och vikt. Syftet med arbetet är att undersöka transporter av betongelement på en industri. Elementen ska framföras säkert och tidseffektivt. Målet är att minimera risken för arbetsrelaterade skador genom att konstruera en ny lastanordning. Konstruktionen ska även främja en mer tidseffektiv hantering än dagens situation. Studien är kvalitativ då forskningen är baserad vid ett fallstudieobjekt. Däremot är både datainsamlingen kvalitativ och kvantitativ. Forskningen resulterade i dels ett koncept med en rälsgående A-bock, dels ett koncept med en A-bock anpassad för transport med dragtruck. Vid simulering av koncepten var resultatet positivt då båda koncepten uppnådde en säkerhetsfaktor av 1,25-4 i relation till materialets sträckgräns.
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An integrated framework for performance measurement in small and medium enterprises : the case of Cape Metropole, South AfricaMabesele, Lindiwe Albertina 12 1900 (has links)
Performance measurement has been in existence and the subject of research for at least two decades. However, it would appear that the Small and Medium Enterprise (SME) sector lags behind other industries in terms of harnessing performance measurement with strategies that call for design skills, such as design thinking. Scholars in developed economies have given only limited attention to the contributing role of design thinking in performance measurement and improvement. Most research in these disciplines focuses primarily on using design thinking during the design phase rather than integrating it throughout the performance measurement processes. However, integrated performance measurement is now receiving increasing attention within the SME context internationally due to the potential benefit of design thinking for strategy. However, while research on performance measurement within South African SMEs is growing, it nevertheless lacks practical perspectives. This is cause for concern, as an absence of knowledge about and understanding of processes followed during performance measurement could deprive the SME sector of the benefit of integrating design thinking for organisation sustainability.
Empirical data were collected from fourteen SMEs using semi-structured interviews, case and documentary analysis and focus group discussions conducted with owner-managers, and analysed. The findings indicate that both contextual and conceptual factors contribute to enterprise performance, and that understanding the processes, performance and execution and tracing their effect on performance measurement are vital. Four process phases of an integrated performance measurement framework emerged from the analysis, namely pre-strategy planning, strategy planning, strategy implementation and post-strategy implementation. These trigger actions which guide and support interaction between leadership and stakeholders and encourage iteration between thinking, trying and the actual discovery of key drivers to monitor, improve and change performance. The findings suggest that the integration of performance measurement is possible with some balanced scorecard and design thinking-related principles engendered in whichever process is deemed natural to configure, improve and evolve by this iteration between thinking and acting. The implications, therefore, include the need for commitment by SMEs to facilitating performance measurement initiatives within their current practices. In addition, the owners or managers and policymakers need to consider ways to assist and play a role in promoting and enhancing the ability of SMEs in performance measurement integration for sustainability. / Isilinganiso sokusebenza besikhona futhi besiyisihloko yocwaningo okungenani amashumi amabili eminyaka. Kodwa-ke, kuzovela ukuthi umkhakha Wamabhizinisi Amancane Naphakathi (SME) usalela emuva kwezinye izimboni maqondana nokusebenzisa isilinganiso sokusebenza ngamasu adinga amakhono wokuklama, njengokucabanga kokuklama. Izazi emnothweni othuthukile zinikeze ukunakwa okulinganiselwe kuphela endimeni ebambe iqhaza ekucabangeni kokuklama esilinganisweni sokusebenza nokwenza ngcono. Ucwaningo oluningi kulezi zimiso lugxile kakhulu ekusebenziseni ukucabanga kokuklama ngesikhathi sesigaba sokuklama kunokuluhlanganisa phakathi kwezinqubo zokulinganisa ukusebenza.
Kodwa-ke, isilinganiso sokusebenza esihlanganisiwe manje sithola ukunakwa okwandayo ngaphakathi komongo wama-SME emhlabeni jikelele ngenxa yenzuzo engaba khona yokucabanga kokuklama kwesu. Kodwa-ke, ngenkathi ucwaningo lwesilinganiso sokusebenza ngaphakathi kwamaSME aseNingizimu Afrika lukhula, kodwa-ke luswele imibono ebonakalayo. Lokhu kuyimbangela yokukhathazeka, njengoba ukungabi bikho kolwazi nokuqonda izinqubo ezilandelwe ngesikhathi sokulinganisa ukusebenza kungancisha umkhakha wama-SME inzuzo yokuhlanganisa ukucabanga kokuklama ukuze kube nokusimama kwenhlangano.
Ulwazi oluqhamuka ocwaningweni laqoqwa kuma-SME ayishumi nane kusetshenziswa izingxoxo ezihleleke kancane, ukuhlaziywa kwamacala kanye nokuqoshwa kwemibhalo kanye nezingxoxo zamaqembu okugxila ezenziwa nabaphathi babanikazi, kwahlaziywa. Okutholakele kukhombisa ukuthi zombili izinto ezingokomongo nezingokomqondo zinomthelela ekusebenzeni komkhakha wamabhizinisi, nokuthi ukuqonda izinqubo, ukusebenza nokwenziwa kanye nokuthola imiphumela yazo esilinganisweni sokusebenza kubalulekile. Izigaba ezine zenqubo zohlaka lokulinganisa ukusebenza oluhlanganisiwe luvele ekuhlaziyweni, okungukuthi ukuhlela kwangaphambi kwamasu, ukuhlela amasu, ukuqaliswa kwamasu nokuqaliswa kwesu langemva kwesu. Lezi zenzo ezibangela ukuhola nokusekela ukuxhumana phakathi kobuholi kanye nababambiqhaza futhi zikhuthaza ukuphindaphinda kwenqubo phakathi kokucabanga, ukuzama kanye nokutholakala kwangempela kwabashayeli ababalulekile ukuqapha, ukwenza ngcono nokushintsha ukusebenza. Okutholakele kuphakamisa ukuthi ukuhlanganiswa kwesilinganiso sokusebenza kungenzeka ngekhadi lamaphuzu elilinganisiwe kanye nezimiso ezihlobene nokucabanga ezifakiwe kunoma iyiphi inqubo ethathwa njengeyokwemvelo yokulungisa, ukwenza ngcono nokuguquka ngaloku kuphindaphinda kwenqubo phakathi kokucabanga nokwenza. Imiphumela, ngakho-ke, ifaka isidingo sokuzibophezela kwama-SME ekusizeni izinhlelo zokulinganisa ukusebenza ngokwenziwa kwazo kwamanje. Ngaphezu kwalokho, abanikazi noma abaphathi nabenzi benqubomgomo kudingeka bacabangele izindlela zokusiza nokudlala indima ekukhuthazeni nasekuthuthukiseni ikhono lama-SME ekuhlanganisweni kwesilinganiso sokusebenza ukuze lisimame. / Prestasiemeting bestaan reeds, en is ook die onderwerp van navorsing, vir minstens twee dekades. Nogtans lyk dit asof die sektor vir Klein en Middelslagondernemings (KMO's) ’n agterstand teenoor ander nywerhede het wat betref die benutting van prestasiemeting met strategieë wat gebruik maak van ontwerpvaardighede soos ontwerpdenke. Navorsers in ontwikkelde ekonomieë het slegs beperkte aandag geskenk aan die bydraende rol van ontwerpdenke in prestasiemeting en -verbetering. Die meeste navorsing in hierdie dissiplines fokus tydens die ontwerpfase hoofsaaklik op die gebruik van ontwerpdenke, in plaas daarvan om dit deurgaans met die prestasie-metingsprosesse te integreer. Geïntegreerde prestasiemeting geniet egter nou toenemende internasionale aandag binne die KMO-konteks, weens die moontlike strategiese voordele van ontwerpdenke. Terwyl navorsing oor prestasiemeting egter in Suid-Afrikaanse KMO's groei, ontbreek daar nogtans praktiese perspektiewe. Dit is kommerwekkend, aangesien 'n gebrek aan kennis oor en begrip van prosesse wat tydens prestasiemeting gevolg word die KMO-sektor kan ontneem van die voordele van geïntegreerde denke vir organisatoriese volhoubaarheid.
Empiriese data is van veertien KMO's ingesamel deur die gebruik van semi-gestruktureerde onderhoude, gevalle- en dokumentêre-ontleding, asook fokusgroepbesprekings wat met eienaarbestuurders gevoer en daarna ontleed is. Die bevindinge dui aan dat beide kontekstuele en konseptuele faktore tot prestasies van ’n onderneming bydra en dat begrip vir die prosesse en werksverrigting, asook die uitvoering en opsporing van die uitwerking daarvan op prestasiemeting, noodsaaklik is. Vier prosedurefases van 'n geïntegreerde prestasiemetingsraamwerk het uit hierdie ontleding het na vore gekom, naamlik pre-strategiebeplanning, strategiebeplanning, strategie-implementering en post-strategie implementering. Hierdie fases veroorsaak aksies wat interaksie tussen leierskap en belanghebbendes lei en ondersteun, en moedig iterasie tussen denke, strewe en die werklike ontdekking van sleuteldrywers aan om prestasie te monitor, verbeter en verander. Die bevindings dui daarop dat die integrasie van prestasiemeting moontlik is met ’n tipe gebalanseerde telkaart en sommige ontwerpverwante denkbeginsels wat aangekweek word in watter proses ook al beskou word as die natuurlike om te konfigureer, verbeter en ontwikkel deur hierdie iterasie tussen denke en aksie. Die implikasies sluit dus die behoefte in van ’n onderneming deur KMO's om prestasiemetingsinisiatiewe in hul huidige praktyke te fasiliteer. Daarbenewens moet die eienaars of bestuurders en beleidmakers oorweging skenk aan maniere om te help en ’n rol te speel in die bevordering en verbetering van KMO’s se vermoëns om prestasiemeting vir volhoubaarheid te integreer / College of Accounting Sciences / D. Phil. (Accounting Sciences)
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