979 resultados para Co-regulated chromosomal domains


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The CDKN2 gene, encoding the cyclin-dependent kinase inhibitor p16, is a tumour suppressor gene that maps to chromosome band 9p21-p22. The most common mechanism of inactivation of this gene in human cancers is through homozygous deletion; however, in a smaller proportion of tumours and tumour cell lines intragenic mutations occur. In this study we have compiled a database of over 120 published point mutations in the CDKN2 gene from a wide variety of tumour types. A further 50 deletions, insertions, and splice mutations in CDKN2 have also been compiled. Furthermore, we have standardised the numbering of all mutations according to the full-length 156 amino acid form of p16. From this study we are able to define several hot spots, some of which occur at conserved residues within the ankyrin domains of p16. While many of the hotspots are shared by a number of cancers, the relative importance of each position varies, possibly reflecting the role of different carcinogens in the development of certain tumours. As reported previously, the mutational spectrum of CDKN2 in melanomas differs from that of internal malignancies and supports the involvement of UV in melanoma tumorigenesis. Notably, 52% of all substitutions in melanoma-derived samples occurred at just six nucleotide positions. Nonsense mutations comprise a comparatively high proportion of mutations present in the CDKN2 gene, and possible explanations for this are discussed.

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Although germline mutations in CDKN2A are present in approximately 25% of large multicase melanoma families, germline mutations are much rarer in the smaller melanoma families that make up most individuals reporting a family history of this disease. In addition, only three families worldwide have been reported with germline mutations in a gene other than CDKN2A (i.e., CDK4). Accordingly, current genomewide scans underway at the National Human Genome Research Institute hope to reveal linkage to one or more chromosomal regions, and ultimately lead to the identification of novel genes involved in melanoma predisposition. Both CDKN2A and PTEN have been identified as genes involved in sporadic melanoma development; however, mutations are more common in cell lines than uncultured tumors. A combination of cytogenetic, molecular, and functional studies suggests that additional genes involved in melanoma development are located to chromosomal regions 1p, 6q, 7p, 11q, and possibly also 9p and 10q. With the near completion of the human genome sequencing effort, combined with the advent of high throughput mutation analyses and new techniques including cDNA and tissue microarrays, the identification and characterization of additional genes involved in melanoma pathogenesis seem likely in the near future.

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Abstract OBJECTIVE: Depression, anxiety and alcohol misuse frequently co-occur. While there is an extensive literature reporting on the efficacy of psychological treatments that target depression, anxiety or alcohol misuse separately, less research has examined treatments that address these disorders when they co-occur. We conducted a systematic review to determine whether psychological interventions that target alcohol misuse among people with co-occurring depressive or anxiety disorders are effective. DATA SOURCES: We systematically searched the PubMed and PsychINFO databases from inception to March 2010. Individual searches in alcohol, depression and anxiety were conducted, and were limited to 'human' published 'randomized controlled trials' or 'sequential allocation' articles written in English. STUDY SELECTION: We identified randomized controlled trials that compared manual guided psychological interventions for alcohol misuse among individuals with depressive or anxiety disorders. Of 1540 articles identified, eight met inclusion criteria for the review. DATA EXTRACTION: From each study, we recorded alcohol and mental health outcomes, and other relevant clinical factors including age, gender ratio, follow-up length and drop-out rates. Quality of studies was also assessed. DATA SYNTHESIS: Motivational interviewing and cognitive-behavioral interventions were associated with significant reductions in alcohol consumption and depressive and/or anxiety symptoms. Although brief interventions were associated with significant improvements in both mental health and alcohol use variables, longer interventions produced even better outcomes. CONCLUSIONS: There is accumulating evidence for the effectiveness of motivational interviewing and cognitive behavior therapy for people with co-occurring alcohol and depressive or anxiety disorders.

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National Housing Relics and Scenic Sites (NHRSSs) in China are the equivalent of National Parks in the West but have contrasting features and broader roles when compared to their Western counterparts. By reviewing and analysing more than 370 academic sources, this paper identifies 6 major issue clusters and future challenges that will influence the management of NHRSSs over time. It also provides a number of cases to illustrate the particular features of NHRSSs. Identifying the hot issues and important challenges in Chinese NHRSSs will provide valuable insights into priorities now being discussed in highly populated areas of the World.

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To identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR-211. We focused on this pigment-cell-enriched miRNA as it is derived from the microphthalmia-associated transcription factor (MITF)-regulated gene, TRPM1 (melastatin). We find that miR-211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR-211, including POU3F2 (BRN2). Inhibition of miR-211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR-211 represses BRN2 in differentiated cells. Over-expression of miR-211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting BRN2 translation. We propose a model for the apparent non-overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR-211 expression.

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Nanostructured tungsten oxide thin film based gas sensors have been developed by thermal evaporation method to detect CO at low operating temperatures. The influence of Fe-doping and annealing heat treatment on microstructural and gas sensing properties of these films have been investigated. Fe was incorporated in WO3 film by co-evaporation and annealing was performed at 400oC for 2 hours in air. AFM analysis revealed a grain size of about 10-15 nm in all the films. GIXRD analysis showed that as-deposited films are amorphous and annealing at 400oC improved the crystallinity. Raman and XRD analysis indicated that Fe is incorporated in the WO3 matrix as a substitutional impurity, resulting in shorter O-W-O bonds and lattice cell parameters. Doping with Fe contributed significantly towards CO sensing performance of WO3 thin films. A good response to various concentrations (10-1000 ppm) of CO has been achieved with 400oC annealed Fe-doped WO3 film at a low operating temperature of 150oC.

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Customer perceived value is concerned with the experiences of consumers when using a service and is often referred to in the context of service provision or on the basis of service quality (Auh, et al., 2007; Chang, 2008; Jackson, 2007; Laukkanen, 2007; Padgett & Mulvey, 2007; Shamdasani, Mukherjee & Malhotra, 2008). Understanding customer perceived value has benefits for social marketing and allows scholars and practitioners alike to identify why consumers engage in positive social behaviours through the use of services. Understanding consumers’ use of wellness services in particular is important, because the use of wellness services demonstrates the fulfilment of social marketing aims; performing pro-active, positive social behaviours that are of benefit to the individual and to society (Andreasen, 1994). As consumers typically act out of self-interest (Rothschild, 1999), this research posits that a value proposition must be made to consumers in order to encourage behavioural change. Thus, this research seeks to identify how value is created for consumers of wellness services in social marketing. This results in the overall research question of this research: How is value created in social marketing wellness services? A traditional method towards understanding value has been the adoption of an economic approach, which considers the utility gained and where value is a direct outcome of a cost-benefit analysis (Payne & Holt, 1999). However, there has since been a shift towards the adoption of an experiential approach in understanding value. This experiential approach considers the consumption experience of the consumer which extends beyond the service exchange and includes pre- and post-consumption stages (Russell-Bennett, Previte & Zainuddin, 2009). As such, this research uses an experiential approach to identify the value that exists in social marketing wellness services. Four dimensions of value have been commonly conceptualised and identified in the commercial marketing literature; functional, emotional, social, and altruistic value (Holbrook, 1994; Sheth, Newman & Gross, 1991; Sweeney & Soutar, 2001). It is not known if these value dimensions also exist in social marketing. In addition, sources of value said to influence value dimensions have been conceptualised in the literature. Sources of value such as information, interaction, environment, service, customer co-creation, and social mandate have been conceptually identified both in the commercial and social marketing literature (Russell-Bennet, Previte & Zainuddin, 2009; Smith & Colgate, 2007). However, it is not clear which sources of value contribute to the creation of value for users of wellness services. Thus, this research seeks to explore these relationships. This research was conducted using a wellness service context, specifically breast cancer screening services. The primary target consumer of these services is women aged 50 to 69 years old (inclusive) who have never been diagnosed with breast cancer. It is recommended that women in this target group have a breast screen every 2 years in order to achieve the most effective medical outcomes from screening. A two-study mixed method approach was utilised. Study 1 was a qualitative exploratory study that analysed individual-depth interviews with 25 information-rich respondents. The interviews were transcribed verbatim and analysed using NVivo 8 software. The qualitative results provided evidence of the existence of the four value dimensions in social marketing. The results also allowed for the development of a typology of experiential value by synthesising current understanding of the value dimensions, with the activity aspects of experiential value identified by Holbrook (1994) and Mathwick, Malhotra and Rigdon (2001). The qualitative results also provided evidence for the existence of sources of value in social marketing, namely information, interaction, environment and consumer participation. In particular, a categorisation of sources of value was developed as a result of the findings from Study 1, which identify organisational, consumer, and third party sources of value. A proposed model of value co-creation and a set of hypotheses were developed based on the results of Study 1 for further testing in Study 2. Study 2 was a large-scale quantitative confirmatory study that sought to test the proposed model of value co-creation and the hypotheses developed. An online-survey was administered Australia-wide to women in the target audience. A response rate of 20.1% was achieved, resulting in a final sample of 797 useable responses after removing ineligible respondents. Reliability and validity analyses were conducted on the data, followed by Exploratory Factor Analysis (EFA) in PASW18, followed by Confirmatory Factor Analysis (CFA) in AMOS18. Following the preliminary analyses, the data was subject to Structural Equation Modelling (SEM) in AMOS18 to test the path relationships hypothesised in the proposed model of value creation. The SEM output revealed that all hypotheses were supported, with the exception of one relationship which was non-significant. In addition, post hoc tests revealed seven further significant non-hypothesised relationships in the model. The quantitative results show that organisational sources of value as well as consumer participation sources of value influence both functional and emotional dimensions of value. The experience of both functional and emotional value in wellness services leads to satisfaction with the experience, followed by behavioural intentions to perform the behaviour and use the service again. One of the significant non-hypothesised relationships revealed that emotional value leads to functional value in wellness services, providing further empirical evidence that emotional value features more prominently than functional value for users of wellness services. This research offers several contributions to theory and practice. Theoretically, this research addresses a gap in the literature by using social marketing theory to provide an alternative method of understanding individual behaviour in a domain that has been predominantly investigated in public health. This research also clarifies the concept of value and offers empirical evidence to show that value is a multi-dimensional construct with separate and distinct dimensions. Empirical evidence for a typology of experiential value, as well as a categorisation of sources of value is also provided. In its practical contributions, this research identifies a framework that is the value creation process and offers health services organisations a diagnostic tool to identify aspects of the service process that facilitate the value creation process.

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This paper argues that a possible cause of issues with management education outcomes is the fact that most training models operate from a limited ‘transfer’ metaphor. This theoretical paper contends that by reconceptualising existing models, specifically Holton’s transfer of learning model, to incorporate multiple processes and acknowledge the importance of educator- or trainer-student interaction in co-creating knowledge, there is potential to improve training design and ultimately achieve more satisfactory training outcomes.

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Teacher professional development provided by education advisors as one-off, centrally offered sessions does not always result in change in teacher knowledge, beliefs, attitudes or practice in the classroom. As the mathematics education advisor in this study, I set out to investigate a particular method of professional development so as to influence change in a practising classroom teacher’s knowledge and practices. The particular method of professional development utilised in this study was based on several principles of effective teacher professional development and saw me working regularly in a classroom with the classroom teacher as well as providing ongoing support for her for a full school year. The intention was to document the effects of this particular method of professional development in terms of the classroom teacher’s and my professional growth to provide insights for others working as education advisors. The professional development for the classroom teacher consisted of two components. The first was the co-operative development and implementation of a mental computation instructional program for the Year 3 class. The second component was the provision of ongoing support for the classroom teacher by the education advisor. The design of the professional development and the mental computation instructional program were progressively refined throughout the year. The education advisor fulfilled multiple roles in the study as teacher in the classroom, teacher educator working with the classroom teacher and researcher. Examples of the professional growth of the classroom teacher and the education advisor which occurred as sequences of changes (growth networks, Hollingsworth, 1999) in the domains of the professional world of the classroom teacher and education advisor were drawn from the large body of data collected through regular face-to-face and email communications between the classroom teacher and the education advisor as well as from transcripts of a structured interview. The Interconnected Model of Professional Growth (Clarke & Hollingsworth, 2002; Hollingsworth, 1999) was used to summarise and represent each example of the classroom teacher’s professional growth. A modified version of this model was used to summarise and represent the professional growth of the education advisor. This study confirmed that the method of professional development utilised could lead to significant teacher professional growth related directly to her work in the classroom. Using the Interconnected Model of Professional Growth to summarise and represent the classroom teacher’s professional growth and the modified version for my professional growth assisted with the recognition of examples of how we both changed. This model has potential to be used more widely by education advisors when preparing, implementing, evaluating and following-up on planned teacher professional development activities. The mental computation instructional program developed and trialled in the study was shown to be a successful way of sequencing and managing the teaching of mental computation strategies and related number sense understandings to Year 3 students. This study was conducted in one classroom, with one teacher in one school. The strength of this study was the depth of teacher support provided made possible by the particular method of the professional development, and the depth of analysis of the process. In another school, or with another teacher, this might not have been as successful. While I set out to change my practice as an education advisor I did not expect the depth of learning I experienced in terms of my knowledge, beliefs, attitudes and practices as an educator of teachers. This study has changed the way in which I plan to work as an education advisor in the future.

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This thesis examines consumer initiated value co-creation behaviour in the context of convergent mobile online services using a Service-Dominant logic (SD logic) theoretical framework. It focuses on non-reciprocal marketing phenomena such as open innovation and user generated content whereby new viable business models are derived and consumer roles and community become essential to the success of business. Attention to customers. roles and personalised experiences in value co-creation has been recognised in the literature (e.g., Prahalad & Ramaswamy, 2000; Prahalad, 2004; Prahalad & Ramaswamy, 2004). Similarly, in a subsequent iteration of their 2004 version of the foundations of SD logic, Vargo and Lusch (2006) replaced the concept of value co-production with value co-creation and suggested that a value co-creation mindset is essential to underpin the firm-customer value creation relationship. Much of this focus, however, has been limited to firm initiated value co-creation (e.g., B2B or B2C), while consumer initiated value creation, particularly consumer-to-consumer (C2C) has received little attention in the SD logic literature. While it is recognised that not every consumer wishes to make the effort to engage extensively in co-creation processes (MacDonald & Uncles, 2009), some consumers may not be satisfied with a standard product, instead they engage in the effort required for personalisation that potentially leads to greater value for themselves, and which may benefit not only the firm, but other consumers as well. Literature suggests that there are consumers who do, and as a result initiate such behaviour and expend effort to engage in co-creation activity (e.g., Gruen, Osmonbekov and Czaplewski, 2006; 2007 MacDonald & Uncles, 2009). In terms of consumers. engagement in value proposition (co-production) and value actualisation (co-creation), SD logic (Vargo & Lusch, 2004, 2008) provides a new lens that enables marketing scholars to transcend existing marketing theory and facilitates marketing practitioners to initiate service centric and value co-creation oriented marketing practices. Although the active role of the consumer is acknowledged in the SD logic oriented literature, we know little about how and why consumers participate in a value co-creation process (Payne, Storbacka, & Frow, 2008). Literature suggests that researchers should focus on areas such as C2C interaction (Gummesson 2007; Nicholls 2010) and consumer experience sharing and co-creation (Belk 2009; Prahalad & Ramaswamy 2004). In particular, this thesis seeks to better understand consumer initiated value co-creation, which is aligned with the notion that consumers can be resource integrators (Baron & Harris, 2008) and more. The reason for this focus is that consumers today are more empowered in both online and offline contexts (Füller, Mühlbacher, Matzler, & Jawecki, 2009; Sweeney, 2007). Active consumers take initiatives to engage and co-create solutions with other active actors in the market for their betterment of life (Ballantyne & Varey, 2006; Grönroos & Ravald, 2009). In terms of the organisation of the thesis, this thesis first takes a „zoom-out. (Vargo & Lusch, 2011) approach and develops the Experience Co-Creation (ECo) framework that is aligned with balanced centricity (Gummesson, 2008) and Actor-to-Actor worldview (Vargo & Lusch, 2011). This ECo framework is based on an extended „SD logic friendly lexicon. (Lusch & Vargo, 2006): value initiation and value initiator, value-in-experience, betterment centricity and betterment outcomes, and experience co-creation contexts derived from five gaps identified from the SD logic literature review. The framework is also designed to accommodate broader marketing phenomena (i.e., both reciprocal and non-reciprocal marketing phenomena). After zooming out and establishing the ECo framework, the thesis takes a zoom-in approach and places attention back on the value co-creation process. Owing to the scope of the current research, this thesis focuses specifically on non-reciprocal value co-creation phenomena initiated by consumers in online communities. Two emergent concepts: User Experience Sharing (UES) and Co-Creative Consumers are proposed grounded in the ECo framework. Together, these two theorised concepts shed light on the following two propositions: (1) User Experience Sharing derives value-in-experience as consumers make initiative efforts to participate in value co-creation, and (2) Co-Creative Consumers are value initiators who perform UES. Three research questions were identified underpinning the scope of this research: RQ1: What factors influence consumers to exhibit User Experience Sharing behaviour? RQ2: Why do Co-Creative Consumers participate in User Experience Sharing as part of value co-creation behaviour? RQ3: What are the characteristics of Co-Creative Consumers? To answer these research questions, two theoretical models were developed: the User Experience Sharing Behaviour Model (UESBM) grounded in the Theory of Planned Behaviour framework, and the Co-Creative Consumer Motivation Model (CCMM) grounded in the Motivation, Opportunity, Ability framework. The models use SD logic consistent constructs and draw upon multiple streams of literature including consumer education, consumer psychology and consumer behaviour, and organisational psychology and organisational behaviour. These constructs include User Experience Sharing with Other Consumers (UESC), User Experience Sharing with Firms (UESF), Enjoyment in Helping Others (EIHO), Consumer Empowerment (EMP), Consumer Competence (COMP), and Intention to Engage in User Experience Sharing (INT), Attitudes toward User Experience Sharing (ATT) and Subjective Norm (SN) in the UESBM, and User Experience Sharing (UES), Consumer Citizenship (CIT), Relating Needs of Self (RELS) and Relating Needs of Others (RELO), Newness (NEW), Mavenism (MAV), Use Innovativeness (UI), Personal Initiative (PIN) and Communality (COMU) in the CCMM. Many of these constructs are relatively new to marketing and require further empirical evidence for support. Two studies were conducted to underpin the corresponding research questions. Study One was conducted to calibrate and re-specify the proposed models. Study Two was a replica study to confirm the proposed models. In Study One, data were collected from a PC DIY online community. In Study Two, a majority of data were collected from Apple product online communities. The data were examined using structural equation modelling and cluster analysis. Considering the nature of the forums, the Study One data is considered to reflect some characteristics of Prosumers and the Study Two data is considered to reflect some characteristics of Innovators. The results drawn from two independent samples (N = 326 and N = 294) provide empirical support for the overall structure theorised in the research models. The results in both models show that Enjoyment in Helping Others and Consumer Competence in the UESBM, and Consumer Citizenship and Relating Needs in CCMM have significant impacts on UES. The consistent results appeared in both Study One and Study Two. The results also support the conceptualisation of Co-Creative Consumers and indicate Co-Creative Consumers are individuals who are able to relate the needs of themselves and others and feel a responsibility to share their valuable personal experiences. In general, the results shed light on "How and why consumers voluntarily participate in the value co-creation process?. The findings provide evidence to conceptualise User Experience Sharing behaviour as well as the Co-Creative Consumer using the lens of SD logic. This research is a pioneering study that incorporates and empirically tests SD logic consistent constructs to examine a particular area of the logic – that is consumer initiated value co-creation behaviour. This thesis also informs practitioners about how to facilitate and understand factors that engage with either firm or consumer initiated online communities.

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In Central Queensland Mining Supplies Pty Ltd v Columbia Steel Casting Co Ltd [2011] QSC 183 Applegarth J considered complaints made by the defendant about the approach the plaintiff had taken in its endeavour to comply with its disclosure obligation under r 211 of the Uniform Civil Procedure Rules 1999 (Qld). The judgment also provides an indication of the direction the court is taking in relation to disclosure and document management in matters involving large numbers of documents.

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The in vitro and in vivo degradation properties of poly(lactic-co-glycolic acid) (PLGA) scaffolds produced by two different technologies - thermally induced phase separation (TIPS), and solvent casting and particulate leaching (SCPL) were compared. Over 6 weeks, in vitro degradation produced changes in SCPL scaffold dimension, mass, internal architecture and mechanical properties. TIPS scaffolds produced far less changes in these parameters providing significant advantages over SCPL. In vivo results were based on a microsurgically created arteriovenous (AV) loop sandwiched between two TIPS scaffolds placed in a polycarbonate chamber under rat groin skin. Histologically, a predominant foreign body giant cell response and reduced vascularity was evident in tissue ingrowth between 2 and 8 weeks in TIPS scaffolds. Tissue death occurred at 8 weeks in the smallest pores. Morphometric comparison of TIPS and SCPL scaffolds indicated slightly better tissue ingrowth but greater loss of scaffold structure in SCPL scaffolds. Although advantageous in vitro, large surface area:volume ratios and varying pore sizes in PLGA TIPS scaffolds mean that effective in vivo (AV loop) utilization will only be achieved if the foreign body response can be significantly reduced so as to allow successful vascularisation, and hence sustained tissue growth, in pores less than 300 μm. © 2005 Elsevier Ltd. All rights reserved.

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If Project Management (PM) is a well-accepted mode of managing organizations, more and more organizations are adopting PM in order to satisfy the diversified needs of application areas within a variety of industries and organizations. Concurrently, the number of PM practitioners and people involved at various level of qualification is vigorously rising. Thus the importance to characterize, define and understand this field and its underlying strength, basis and development is paramount. For this purpose we will referee to sociology of actor-networks and qualitative scientometrics leading to the choice of the co-word analysis method in enabling us to capture the project management field and its dynamics. Results of a study based on the analysis of EBSCO Business Source Premier Database will be presented and some future trends and scenarios proposed. The main following trends are confirmed, in alignment with previous studies: continuous interest for the “cost engineering” aspects, on going interest for Economic aspects and contracts, how to deal with various project types (categorizations), the integration with Supply Chain Management and Learning and Knowledge Management. Furthermore besides these continuous trends, we can note new areas of interest: the link between strategy and project, Governance, the importance of maturity (organizational performance and metrics, control) and Change Management. We see the actors (Professional Bodies, Governmental Bodies, Agencies, Universities, Industries, Researchers, and Practitioners) reinforcing their competing/cooperative strategies in the development of standards and certifications and moving to more “business oriented” relationships with their members and main stakeholders (Governments, Institutions like European Community, Industries, Agencies, NGOs…), at least at central level.

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A 4-cylinder Ford 2701C test engine was used in this study to explore the impact of ethanol fumigation on gaseous and particle emission concentrations. The fumigation technique delivered vaporised ethanol into the intake manifold of the engine, using an injector, a pump and pressure regulator, a heat exchanger for vaporising ethanol and a separate fuel tank and lines. Gaseous (Nitric oxide (NO), Carbon monoxide (CO) and hydrocarbons (HC)) and particulate emissions (particle mass (PM2.5) and particle number) testing was conducted at intermediate speed (1700 rpm) using 4 load settings with ethanol substitution percentages ranging from 10-40 % (by energy). With ethanol fumigation, NO and PM2.5 emissions were reduced, whereas CO and HC emissions increased considerably and particle number emissions increased at most test settings. It was found that ethanol fumigation reduced the excess air factor for the engine and this led to increased emissions of CO and HC, but decreased emissions of NO. PM2.5 emissions were reduced with ethanol fumigation, as ethanol has a very low “sooting” tendency. This is due to the higher hydrogen-to-carbon ratio of this fuel, and also because ethanol does not contain aromatics, both of which are known soot precursors. The use of a diesel oxidation catalyst (as an after-treatment device) is recommended to achieve a reduction in the four pollutants that are currently regulated for compression ignition engines. The increase in particle number emissions with ethanol fumigation was due to the formation of volatile (organic) particles; consequently, using a diesel oxidation catalyst will also assist in reducing particle number emissions.