11 research outputs found
Stakeholders’ Participation in the Creative Economic Development of Cirebon City
Get PDFThis study aims to examine the participation level of stakeholders, identify the dominant stakeholders, and investigate the factors inhibiting stakeholders’ participation in the planning, implementation, and evaluation of creative economic development in Cirebon City. “Creative City” is politically and legally stipulated as the city vision in the regional mid-term development plan 2018-2023 of Cirebon City. As the creative economy is centered around the production, exchanges, and consumption of goods and services from human creativity, Cirebon City is, therefore, a significant case study to investigate how the local government implements participatory processes in developing a creative city.Using qualitative methods, data were collected through a semi-guided interview of 190 respondents from five stakeholders: academics, businesses, communities, government institutions, and media organizations. It was followed by a focus group discussion of 12 key respondents selected purposively from the five stakeholders. With primary and secondary data sources, qualitative data was analyzed through the process of data reduction, data display, and conclusion drawing/verification.This study concluded that stakeholders' participation in all stages of creative economic development in Cirebon was still minimal. The businesses in culinary subsectors as the most dominant stakeholders in the participation processes. The lack of socialization from the municipal government and the limited collaboration amongst the stakeholders were identified as the inhibiting factors of inclusive participation in creative city development. The government needs to accelerate creative economic development through multisectoral policies, including improvement of business knowledge and skills of the local business actors, goods and services’ quality upgrading and assurance, certification and legal assistance, as well as promotion and market expansionKnown for its rich cultural heritage, Cirebon City was one of the hubs of Indonesia’s creative economy. The creative economic development in Cirebon was a response to the aspirations of the local community, who were eager to showcase their unique heritage and history, as stated in the city vision in its regional mid-term development plan for 2018-2023. This study aimed to examine the participation level of stakeholders, identify the dominant stakeholders, and investigate the factors inhibiting stakeholders’ participation in the planning, implementation, and evaluation of creative economic development in Cirebon City. Since the creative economy revolved around the production, exchanges, and consumption of goods and services stemming from human creativity, Cirebon City served a significant case study for investigating how its local government implemented participatory processes in developing a creative city. Using qualitative methods, data were collected through a semi-guided interview of 190 respondents from five stakeholders: academics, businesses, communities, government institutions, and media organisations. It was followed by a focus group discussion of 12 key respondents selected purposively from the five stakeholders. With primary and secondary data sources, qualitative data was analysed through the processes of data reduction, data display, and conclusion drawing/verification. This study concluded that stakeholders' participation in all stages of creative economic development in Cirebon was still minimal. The businesses in the culinary subsectors were the most dominant stakeholders in the participation processes. The lack of socialisation from the municipal government and the limited collaboration amongst the stakeholders were identified as the inhibiting factors of inclusive participation in creative city development. The government needs to accelerate creative economic development through multisectoral policies, including improvement of business knowledge and skills of the local business actors, goods and services’ quality upgrading and assurance, certification and legal assistance, and promotion and market expansion
In Vitro and In Vivo Catabolite Profiles of Leuprorelin in Rat and the Effects of NADPH in Leuprorelin Catabolism
Get PDFAbstract
Purpose:
The catabolism of leuprorelin was studied in rat-derived hepatic and extrahepatic in vitro models and in vivo to compare the catabolism with human models and to evaluate whether the earlier reported NADPH-dependency of leuprorelin catabolism affects in vivo correlation. Furthermore, the mechanism of NADPH-dependency was investigated with human and rat-derived models.
Methods:
Leuprorelin was incubated with rat hepatic and extrahepatic in vitro models. Additionally, leuprorelin was dosed into rats to determine what in vitro system provided the best correlation with in vivo. Lastly, leuprorelin was incubated with rat and human derived enzyme sources to identify the processes responsible for NADPH-dependent catabolism. The analysis was performed with UPLC-HRMS.
Results:
The same NADPH-dependency of leuprorelin catabolism as in human was observed with rat liver and kidney S9 fraction. Furthermore, the best in vitro – in vivo correlation was provided by the incubation with kidney S9 fraction in the absence of NADPH. The catabolite profiles produced in the incubations with the employed rat and human sub-cellular fractions supplemented with NADPH were replicable with the addition of DTT in the incubations. Therefore, the NADPH-dependency was not caused by metabolic enzymes, but rather by processes maintaining the reductive potential of the cell, activating peptidases responsible for the catabolism of leuprorelin.
Conclusion:
The influence of DTT on the peptidase activity has been known, but the NADPH-dependency of the therapeutic peptide catabolism is novel, and more research is needed to assess the importance of this effect on in vitro – in vivo correlation for other therapeutic peptides.Abstract
Purpose:
The catabolism of leuprorelin was studied in rat-derived hepatic and extrahepatic in vitro models and in vivo to compare the catabolism with human models and to evaluate whether the earlier reported NADPH-dependency of leuprorelin catabolism affects in vivo correlation. Furthermore, the mechanism of NADPH-dependency was investigated with human and rat-derived models.
Methods:
Leuprorelin was incubated with rat hepatic and extrahepatic in vitro models. Additionally, leuprorelin was dosed into rats to determine what in vitro system provided the best correlation with in vivo. Lastly, leuprorelin was incubated with rat and human derived enzyme sources to identify the processes responsible for NADPH-dependent catabolism. The analysis was performed with UPLC-HRMS.
Results:
The same NADPH-dependency of leuprorelin catabolism as in human was observed with rat liver and kidney S9 fraction. Furthermore, the best in vitro – in vivo correlation was provided by the incubation with kidney S9 fraction in the absence of NADPH. The catabolite profiles produced in the incubations with the employed rat and human sub-cellular fractions supplemented with NADPH were replicable with the addition of DTT in the incubations. Therefore, the NADPH-dependency was not caused by metabolic enzymes, but rather by processes maintaining the reductive potential of the cell, activating peptidases responsible for the catabolism of leuprorelin.
Conclusion:
The influence of DTT on the peptidase activity has been known, but the NADPH-dependency of the therapeutic peptide catabolism is novel, and more research is needed to assess the importance of this effect on in vitro – in vivo correlation for other therapeutic peptides
INVENTORY AND TOURISM OPPORTUNITIES IN SEKUPANG – BATAM DISTRICT
No full textBatam in developing tourism through the activities of the types of tourism that exist inevery places of Batam, one of which is located in Sekupang District. Sekupang District with 7 existing urban villages, has tourism potential but not yet maximally in the process of inventory of tourism potential which can be a chance of one of the superior products of tourism as well as increase the splendor of Batam tourism. Opportunities and potential of tourism can be seen through the following attractions (attractiveness), accesable (system achieved), amenities (facilities), ancillary (tourism institutions). Opportunities and potentials that can be made in the development of tourism Sekupang District and make Sekupang district can contribute in Batam tourism through the potential of existing tourism.Key Words: tourism indentification, tourism opportunity, community based tourism
Erratum : The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma (Cell Reports (2018) 23(1) (313–326.e5) (S2211124718304364) (10.1016/j.celrep.2018.03.075))
Get PDF(Cell Reports 23, 313–326; April 3, 2018) In the originally published version of this article, the author list contained two errors. Specifically, David J. Kwiatkowski was misspelled as David J. Kwaitkowski, and William Y. Kim was inadvertently written as William T. Kim. Both names have been corrected online. The authors regret this error
Aldehyde oxidase 1 activity and protein expression in human, rabbit, and pig ocular tissues
No full textAldehyde oxidase (AOX) is a cytosolic drug-metabolizing enzyme which has attracted increasing attention in drug development due to its high hepatic expression, broad substrate profile and species differences. In contrast, there is limited information on the presence and activity of AOX in extrahepatic tissues including ocular tissues. Because several ocular drugs are potential substrates for AOX, we performed a comprehensive analysis of the AOX1 expression and activity profile in seven ocular tissues from humans, rabbits, and pigs. AOX activities were determined using optimized assays for the established human AOX1 probe substrates 4-dimethylamino-cinnamaldehyde (DMAC) and phthalazine. Inhibition studies were undertaken in conjunctival and retinal homogenates using well-established human AOX1 inhibitors menadione and chlorpromazine. AOX1 protein contents were quantitated with targeted proteomics and confirmed by immunoblotting. Overall, DMAC oxidation rates varied over 10-fold between species (human >> rabbit > pig) and showed 2- to 6-fold differences between tissues from the same species. Menadione seemed a more potent inhibitor of DMAC oxidation across species than chlorpromazine. Human AOX1 protein levels were highest in the conjunctiva, followed by most posterior tissues, whereas anterior tissues showed low levels. The rabbit AOX1 expression was high in the conjunctiva, retinal pigment epithelial (RPE), and choroid while lower in the anterior tissues. Quantification of pig AOX1 was not successful but immunoblotting confirmed the presence of AOX1 in all species. DMAC oxidation rates and AOX1 contents correlated quite well in humans and rabbits. This study provides, for the first time, insights into the ocular expression and activity of AOX1 among multiple species.Peer reviewe
Erratum: The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma
No full text(Cell Reports 23, 313–326; April 3, 2018) In the originally published version of this article, the author list contained two errors. Specifically, David J. Kwiatkowski was misspelled as David J. Kwaitkowski, and William Y. Kim was inadvertently written as William T. Kim. Both names have been corrected online. The authors regret this error
Erratum: The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma (Cell Reports (2018) 23(1) (313–326.e5) (S2211124718304364) (10.1016/j.celrep.2018.03.075))
No full text(Cell Reports 23, 313–326; April 3, 2018) In the originally published version of this article, the author list contained two errors. Specifically, David J. Kwiatkowski was misspelled as David J. Kwaitkowski, and William Y. Kim was inadvertently written as William T. Kim. Both names have been corrected online. The authors regret this error
Tumour immune contexture and immune evasion in sporadic and Lynch syndrome-associated microsatellite unstable colorectal cancers
No full textAbstract
Background:
The high mutational burden in microsatellite unstable colorectal cancers (MSI CRCs) results in high immunogenicity, yet response rates to immunotherapy vary, suggesting underlying heterogeneity of the tumour immune landscape. Here, our aims were (1) to characterise the immune cell infiltrate and immune evasion in MSI CRCs, (2) to correlate these with clinical and genomic features, and (3) to compare these between Lynch syndrome (LS) and sporadic MSI CRCs.
Method:
Immunohistochemistry was utilised to detect T cell and myeloid cell subsets. Whole-genome and RNA sequencing were utilised to analyse somatic variants, tumour clonality, neoantigen burden, antigen presentation, immune checkpoint expression, and consensus molecular subtypes.
Results:
Our results revealed higher immune cell scores in LS tumours, depicting higher T cell infiltration, compared to sporadic tumours. Conversely, sporadic tumours displayed increased infiltration of protumorigenic M2-like macrophages and increased expression of immune checkpoints PDCD1LG2 and CD40LG. Across our MSI CRC cohort, high neoantigen burden was associated with low tumour clonality.
Conclusions:
Our findings reveal differences between sporadic MSI and LS tumours in T cell and myeloid immune cell landscapes, and in immune evasion. These differences may contribute to the variable immunotherapy responses among MSI CRC patients and are targetable by emerging therapeutic approaches.Abstract
Background:
The high mutational burden in microsatellite unstable colorectal cancers (MSI CRCs) results in high immunogenicity, yet response rates to immunotherapy vary, suggesting underlying heterogeneity of the tumour immune landscape. Here, our aims were (1) to characterise the immune cell infiltrate and immune evasion in MSI CRCs, (2) to correlate these with clinical and genomic features, and (3) to compare these between Lynch syndrome (LS) and sporadic MSI CRCs.
Method:
Immunohistochemistry was utilised to detect T cell and myeloid cell subsets. Whole-genome and RNA sequencing were utilised to analyse somatic variants, tumour clonality, neoantigen burden, antigen presentation, immune checkpoint expression, and consensus molecular subtypes.
Results:
Our results revealed higher immune cell scores in LS tumours, depicting higher T cell infiltration, compared to sporadic tumours. Conversely, sporadic tumours displayed increased infiltration of protumorigenic M2-like macrophages and increased expression of immune checkpoints PDCD1LG2 and CD40LG. Across our MSI CRC cohort, high neoantigen burden was associated with low tumour clonality.
Conclusions:
Our findings reveal differences between sporadic MSI and LS tumours in T cell and myeloid immune cell landscapes, and in immune evasion. These differences may contribute to the variable immunotherapy responses among MSI CRC patients and are targetable by emerging therapeutic approaches
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The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma
No full text(Cell Reports 23, 313–326; April 3, 2018) In the originally published version of this article, the author list contained two errors. Specifically, David J. Kwiatkowski was misspelled as David J. Kwaitkowski, and William Y. Kim was inadvertently written as William T. Kim. Both names have been corrected online. The authors regret this error
Erratum: The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma (Cell Reports (2018) 23(1) (313–326.e5) (S2211124718304364) (10.1016/j.celrep.2018.03.075))
No full text(Cell Reports 23, 313–326; April 3, 2018) In the originally published version of this article, the author list contained two errors. Specifically, David J. Kwiatkowski was misspelled as David J. Kwaitkowski, and William Y. Kim was inadvertently written as William T. Kim. Both names have been corrected online. The authors regret this error
