Prediction of transcriptional regulatory interactions in bacteria : a comparative genomics approach

Exponential growth of genomic data in the last two decades has made manual analyses impractical for all but trial studies. As genomic analyses have become more sophisticated, and move toward comparisons across large datasets, computational approaches have become essential. One of the most important biological questions is to understand the mechanisms underlying gene regulation. Genetic regulation is commonly investigated and modelled through the use of transcriptional regulatory network (TRN) structures. These model the regulatory interactions between two key components: transcription factors (TFs) and the target genes (TGs) they regulate. Transcriptional regulatory networks have proven to be invaluable scientific tools in Bioinformatics. When used in conjunction with comparative genomics, they have provided substantial insights into the evolution of regulatory interactions. Current approaches to regulatory network inference, however, omit two additional key entities: promoters and transcription factor binding sites (TFBSs). In this study, we attempted to explore the relationships among these regulatory components in bacteria. Our primary goal was to identify relationships that can assist in reducing the high false positive rates associated with transcription factor binding site predictions and thereupon enhance the reliability of the inferred transcription regulatory networks. In our preliminary exploration of relationships between the key regulatory components in Escherichia coli transcription, we discovered a number of potentially useful features. The combination of location score and sequence dissimilarity scores increased de novo binding site prediction accuracy by 13.6%. Another important observation made was with regards to the relationship between transcription factors grouped by their regulatory role and corresponding promoter strength. Our study of E.coli ��70 promoters, found support at the 0.1 significance level for our hypothesis | that weak promoters are preferentially associated with activator binding sites to enhance gene expression, whilst strong promoters have more repressor binding sites to repress or inhibit gene transcription. Although the observations were specific to �70, they nevertheless strongly encourage additional investigations when more experimentally confirmed data are available. In our preliminary exploration of relationships between the key regulatory components in E.coli transcription, we discovered a number of potentially useful features { some of which proved successful in reducing the number of false positives when applied to re-evaluate binding site predictions. Of chief interest was the relationship observed between promoter strength and TFs with respect to their regulatory role. Based on the common assumption, where promoter homology positively correlates with transcription rate, we hypothesised that weak promoters would have more transcription factors that enhance gene expression, whilst strong promoters would have more repressor binding sites. The t-tests assessed for E.coli �70 promoters returned a p-value of 0.072, which at 0.1 significance level suggested support for our (alternative) hypothesis; albeit this trend may only be present for promoters where corresponding TFBSs are either all repressors or all activators. Nevertheless, such suggestive results strongly encourage additional investigations when more experimentally confirmed data will become available. Much of the remainder of the thesis concerns a machine learning study of binding site prediction, using the SVM and kernel methods, principally the spectrum kernel. Spectrum kernels have been successfully applied in previous studies of protein classification [91, 92], as well as the related problem of promoter predictions [59], and we have here successfully applied the technique to refining TFBS predictions. The advantages provided by the SVM classifier were best seen in `moderately'-conserved transcription factor binding sites as represented by our E.coli CRP case study. Inclusion of additional position feature attributes further increased accuracy by 9.1% but more notable was the considerable decrease in false positive rate from 0.8 to 0.5 while retaining 0.9 sensitivity. Improved prediction of transcription factor binding sites is in turn extremely valuable in improving inference of regulatory relationships, a problem notoriously prone to false positive predictions. Here, the number of false regulatory interactions inferred using the conventional two-component model was substantially reduced when we integrated de novo transcription factor binding site predictions as an additional criterion for acceptance in a case study of inference in the Fur regulon. This initial work was extended to a comparative study of the iron regulatory system across 20 Yersinia strains. This work revealed interesting, strain-specific difierences, especially between pathogenic and non-pathogenic strains. Such difierences were made clear through interactive visualisations using the TRNDifi software developed as part of this work, and would have remained undetected using conventional methods. This approach led to the nomination of the Yfe iron-uptake system as a candidate for further wet-lab experimentation due to its potential active functionality in non-pathogens and its known participation in full virulence of the bubonic plague strain. Building on this work, we introduced novel structures we have labelled as `regulatory trees', inspired by the phylogenetic tree concept. Instead of using gene or protein sequence similarity, the regulatory trees were constructed based on the number of similar regulatory interactions. While the common phylogentic trees convey information regarding changes in gene repertoire, which we might regard being analogous to `hardware', the regulatory tree informs us of the changes in regulatory circuitry, in some respects analogous to `software'. In this context, we explored the `pan-regulatory network' for the Fur system, the entire set of regulatory interactions found for the Fur transcription factor across a group of genomes. In the pan-regulatory network, emphasis is placed on how the regulatory network for each target genome is inferred from multiple sources instead of a single source, as is the common approach. The benefit of using multiple reference networks, is a more comprehensive survey of the relationships, and increased confidence in the regulatory interactions predicted. In the present study, we distinguish between relationships found across the full set of genomes as the `core-regulatory-set', and interactions found only in a subset of genomes explored as the `sub-regulatory-set'. We found nine Fur target gene clusters present across the four genomes studied, this core set potentially identifying basic regulatory processes essential for survival. Species level difierences are seen at the sub-regulatory-set level; for example the known virulence factors, YbtA and PchR were found in Y.pestis and P.aerguinosa respectively, but were not present in both E.coli and B.subtilis. Such factors and the iron-uptake systems they regulate, are ideal candidates for wet-lab investigation to determine whether or not they are pathogenic specific. In this study, we employed a broad range of approaches to address our goals and assessed these methods using the Fur regulon as our initial case study. We identified a set of promising feature attributes; demonstrated their success in increasing transcription factor binding site prediction specificity while retaining sensitivity, and showed the importance of binding site predictions in enhancing the reliability of regulatory interaction inferences. Most importantly, these outcomes led to the introduction of a range of visualisations and techniques, which are applicable across the entire bacterial spectrum and can be utilised in studies beyond the understanding of transcriptional regulatory networks.

Frame-rate stereopsis using non-parametric transforms and programmable logic

A frame-rate stereo vision system, based on non-parametric matching metrics, is described. Traditional metrics, such as normalized cross-correlation, are expensive in terms of logic. Non-parametric measures require only simple, parallelizable, functions such as comparators, counters and exclusive-or, and are thus very well suited to implementation in reprogrammable logic.

A critical evaluation and comparison of two formative measures of system quality using criterion variables

Evaluating the validity of formative variables has presented ongoing challenges for researchers. In this paper we use global criterion measures to compare and critically evaluate two alternative formative measures of System Quality. One model is based on the ISO-9126 software quality standard, and the other is based on a leading information systems research model. We find that despite both models having a strong provenance, many of the items appear to be non-significant in our study. We examine the implications of this by evaluating the quality of the criterion variables we used, and the performance of PLS when evaluating formative models with a large number of items. We find that our respondents had difficulty distinguishing between global criterion variables measuring different aspects of overall System Quality. Also, because formative indicators “compete with one another” in PLS, it may be difficult to develop a set of measures which are all significant for a complex formative construct with a broad scope and a large number of items. Overall, we suggest that there is cautious evidence that both sets of measures are valid and largely equivalent, although questions still remain about the measures, the use of criterion variables, and the use of PLS for this type of model evaluation.

Mixed convection along a vertical flat plate in a non-absorbing medium

Here mixed convection boundary layer flow of a viscous fluid along a heated vertical semi-infinite plate is investigated in a non-absorbing medium. The relationship between convection and thermal radiation is established via boundary condition of second kind on the thermally radiating vertical surface. The governing boundary layer equations are transformed into dimensionless parabolic partial differential equations with the help of appropriate transformations and the resultant system is solved numerically by applying straightforward finite difference method along with Gaussian elimination technique. It is worthy to note that Prandlt number, Pr, is taken to be small (<< 1) which is appropriate for liquid metals. Moreover, the numerical results are demonstrated graphically by showing the effects of important physical parameters, namely, the modified Richardson number (or mixed convection parameter), Ri*, and surface radiation parameter, R, in terms of local skin friction and local Nusselt number coefficients.

Continuous and non-intrusive identity verification in real-time environments based on free-text keystroke dynamics

Internet services are important part of daily activities for most of us. These services come with sophisticated authentication requirements which may not be handled by average Internet users. The management of secure passwords for example creates an extra overhead which is often neglected due to usability reasons. Furthermore, password-based approaches are applicable only for initial logins and do not protect against unlocked workstation attacks. In this paper, we provide a non-intrusive identity verification scheme based on behavior biometrics where keystroke dynamics based-on free-text is used continuously for verifying the identity of a user in real-time. We improved existing keystroke dynamics based verification schemes in four aspects. First, we improve the scalability where we use a constant number of users instead of whole user space to verify the identity of target user. Second, we provide an adaptive user model which enables our solution to take the change of user behavior into consideration in verification decision. Next, we identify a new distance measure which enables us to verify identity of a user with shorter text. Fourth, we decrease the number of false results. Our solution is evaluated on a data set which we have collected from users while they were interacting with their mail-boxes during their daily activities.

Non-intrusive continuous user behaviour analysis using computerized systems

There are different ways to authenticate humans, which is an essential prerequisite for access control. The authentication process can be subdivided into three categories that rely on something someone i) knows (e.g. password), and/or ii) has (e.g. smart card), and/or iii) is (biometric features). Besides classical attacks on password solutions and the risk that identity-related objects can be stolen, traditional biometric solutions have their own disadvantages such as the requirement of expensive devices, risk of stolen bio-templates etc. Moreover, existing approaches provide the authentication process usually performed only once initially. Non-intrusive and continuous monitoring of user activities emerges as promising solution in hardening authentication process: iii-2) how so. behaves. In recent years various keystroke dynamic behavior-based approaches were published that are able to authenticate humans based on their typing behavior. The majority focuses on so-called static text approaches, where users are requested to type a previously defined text. Relatively few techniques are based on free text approaches that allow a transparent monitoring of user activities and provide continuous verification. Unfortunately only few solutions are deployable in application environments under realistic conditions. Unsolved problems are for instance scalability problems, high response times and error rates. The aim of this work is the development of behavioral-based verification solutions. Our main requirement is to deploy these solutions under realistic conditions within existing environments in order to enable a transparent and free text based continuous verification of active users with low error rates and response times.

Situational non-flammable control valves for oxygen service

Past work has clearly demonstrated that numerous commonly used metallic materials will support burning in oxygen, especially at higher pressures. An approach to rectify this significant safety problem has been successfully developed and implemented by applying the concept of Situational Non-Flammability. This approach essentially removes or breaks one leg of the conceptual fire triangle, a tool commonly used to define the three things that are required to support burning; a fuel, an ignition source and an oxidizer. Since an oxidiser is always present in an oxygen system as are ignition sources, the concept of Situational Non-Flammability essentially removes the fuel leg of the fire triangle by only utilising materials that will not burn at the maximum pressure, for example, that the control valve is to be used in. The utilisation of this approach has lead to the development of a range of oxygen components that are practically unable to burn while in service at their design pressure thus providing an unparalleled level of first safety while not compromising on the performance or endurance required in the function of these components. This paper describes the concept of Situational Non-Flammability, how it was used to theoretically evaluate designs of components for oxygen service and the outcomes of the actual development, fabrication and finally utilisation of these components in real oxygen systems in a range of flow control devices.

The minority report : disproportionate representation in Australia’s largest education system

The overrepresentation of students from minority ethnic groups in separate special education settings has been extensively documented in North America, yet little research exists for Australian school systems. To address this gap, we systematically analyzed 13 years of enrolment data from the state of New South Wales. Stark differences are seen in patterns of enrolment between Indigenous students, students from a Language Background Other than English (LBOTE), and non-Indigenous English speaking students. Moreover, these differences are increasing. While enrollments of Indigenous students in separate settings increased faster across time than did enrollments of Indigenous students in mainstream, enrollments of LBOTE students in mainstream increased faster than did enrollments of LBOTE students in separate settings.

General trajectory prior for non-rigid reconstruction

Trajectory basis Non-Rigid Structure From Motion (NRSFM) currently faces two problems: the limit of reconstructability and the need to tune the basis size for different sequences. This paper provides a novel theoretical bound on 3D reconstruction error, arguing that the existing definition of reconstructability is fundamentally flawed in that it fails to consider system condition. This insight motivates a novel strategy whereby the trajectory's response to a set of high-pass filters is minimised. The new approach eliminates the need to tune the basis size and is more efficient for long sequences. Additionally, the truncated DCT basis is shown to have a dual interpretation as a high-pass filter. The success of trajectory filter reconstruction is demonstrated quantitatively on synthetic projections of real motion capture sequences and qualitatively on real image sequences.

Design, simulation and analysis of a parallel hybrid electric propulsion system for unmanned aerial vehicles

Aerial Vehicles (UAV) has become a significant growing segment of the global aviation industry. These vehicles are developed with the intention of operating in regions where the presence of onboard human pilots is either too risky or unnecessary. Their popularity with both the military and civilian sectors have seen the use of UAVs in a diverse range of applications, from reconnaissance and surveillance tasks for the military, to civilian uses such as aid relief and monitoring tasks. Efficient energy utilisation on an UAV is essential to its functioning, often to achieve the operational goals of range, endurance and other specific mission requirements. Due to the limitations of the space available and the mass budget on the UAV, it is often a delicate balance between the onboard energy available (i.e. fuel) and achieving the operational goals. This paper presents the development of a parallel Hybrid Electric Propulsion System (HEPS) on a small fixed-wing UAV incorporating an Ideal Operating Line (IOL) control strategy. A simulation model of an UAV was developed in the MATLAB Simulink environment, utilising the AeroSim Blockset and the in-built Aerosonde UAV block and its parameters. An IOL analysis of an Aerosonde engine was performed, and the most efficient (i.e. provides greatest torque output at the least fuel consumption) points of operation for this engine were determined. Simulation models of the components in a HEPS were designed and constructed in the MATLAB Simulink environment. It was demonstrated through simulation that an UAV with the current HEPS configuration was capable of achieving a fuel saving of 6.5%, compared to the ICE-only configuration. These components form the basis for the development of a complete simulation model of a Hybrid-Electric UAV (HEUAV).

An influenza virus inspired polymer system for the timed release of siRNA

Small interfering RNA silences specific genes by interfering with mRNA translation, and acts to modulate or inhibit specific biological pathways; a therapy that holds great promise in the cure of many diseases. However, the naked small interfering RNA is susceptible to degradation by plasma and tissue nucleases and due to its negative charge unable to cross the cell membrane. Here we report a new polymer carrier designed to mimic the influenza virus escape mechanism from the endosome, followed by a timed release of the small interfering RNA in the cytosol through a self-catalyzed polymer degradation process. Our polymer changes to a negatively charged and non-toxic polymer after the release of small interfering RNA, presenting potential for multiple repeat doses and long-term treatment of diseases.

A new feedback ANC system approach

We propose a new active noise control (ANC) technique. The technique has a feedback structure to have a simple configuration in practical implementation. In this approach, the secondary path is modelled online to ensure convergence of the system as the secondary paths are practically time varying or non-linear. The proposed method consists of two steps: a noise controller which is based on a modified FxLMS algorithm, and a new variable step size (VSS) LMS algorithm which is used to adapt the modelling filter with the secondary path. The proposed algorithm stops injection of the white noise at the optimum point and reactivate the injection during the operation, if needed, to maintain performance of the system. Eliminating continuous injection of the white noise increases the performance of the proposed method significantly and makes it more desirable for practical ANC systems. The computer simulations are presented to show the effectiveness of the proposed method.

Women as victims and offenders : incarcerated for murder in the Australian criminal justice system

This study was undertaken in an effort to contribute to the limited knowledge of women who commit murder. Women account for approximately 10% of the total Australian homicides and according to Mouzos (2000), 20% of these female perpetrated homicides result in murder convictions. In her extensive study of female homicide offending in England, Brookman (2005) asserts that nearly two thirds of the victims of women who kill are intimates, to include violent partners and their own children. The other third of the victims consist largely of acquaintances and to lesser degree strangers (Brookman, 2005). This study strives to introduce further knowledge regarding women convicted of murder; the smaller subgroup of female homicide offenders of which less is known. It is comprised of women who killed intimates and non-intimates to include acquaintances. The study engages the narratives of seven women, all of whom were convicted of murder and serving lengthy sentences at the Dame Phyllis Frost Centre, a medium and maximum security prison that is located on the outskirts of Melbourne, Australia. The seven women fall largely outside of the characteristics of female homicide offenders as revealed in the studies from Australia’s National Homicide Monitoring Program (NHMP, 2007), from Canada by Hoffmann, Lavigne, and Dickie (1998) and research from the United States by Scott and Davies (2002). In this study there were no Indigenous women represented. Only one of the women had a previous criminal charge. The women were older on average than the prevailing demographics from western nations. Two of the women had substance abuse and co-occurring mental illness, which reflects a significant lower rate than the literature suggests. This study expands the current understanding of the phenomenon of women who murder. It communicates the narratives of seven women charged and convicted of murder as they attempt to understand their lives and identities. It moves the dialogue beyond the preponderance of feminist criminological research that examines motive and the relationship the woman has with her victim to the social discourses which dominate in her identity formation. This research found that in their attempt to create a favourable identity the women needed to engage with the master script of normative femininity through the feminisation of victimisation, motherhood and domesticity.

Comparing cooperative and non-cooperative crash risk assessment

Cooperative Systems provide, through the multiplication of information sources over the road, a lot of potential to improve the assessment of the road risk describing a particular driving situation. In this paper, we compare the performance of a cooperative risk assessment approach against a non-cooperative approach; we used an advanced simulation framework, allowing for accurate and detailed, close-to-reality simulations. Risk is estimated, in both cases, with combinations of indicators based on the TTC. For the non-cooperative approach, vehicles are equipped only with an AAC-like forward-facing ranging sensor. On the other hand, for the cooperative approach, vehicles share information through 802.11p IVC and create an augmented map representing their environment; risk indicators are then extracted from this map. Our system shows that the cooperative risk assessment provides a systematic increase of forward warning to most of the vehicles involved in a freeway emergency braking scenario, compared to a non-cooperative system.

The individual and interactive relationship between long chain omega-3 polyunsaturated fatty acids and physical activity as predictors of cognition in cognitively impaired and non-impaired older adults

Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.