Learning Object-Independent Modes of Variation with Feature Flow Fields

We present a unifying framework in which "object-independent" modes of variation are learned from continuous-time data such as video sequences. These modes of variation can be used as "generators" to produce a manifold of images of a new object from a single example of that object. We develop the framework in the context of a well-known example: analyzing the modes of spatial deformations of a scene under camera movement. Our method learns a close approximation to the standard affine deformations that are expected from the geometry of the situation, and does so in a completely unsupervised (i.e. ignorant of the geometry of the situation) fashion. We stress that it is learning a "parameterization", not just the parameter values, of the data. We then demonstrate how we have used the same framework to derive a novel data-driven model of joint color change in images due to common lighting variations. The model is superior to previous models of color change in describing non-linear color changes due to lighting.

An Algorithm for Group Formation and Maximal Independent Set in an Amorphous Computer

Amorphous computing is the study of programming ultra-scale computing environments of smart sensors and actuators cite{white-paper}. The individual elements are identical, asynchronous, randomly placed, embedded and communicate locally via wireless broadcast. Aggregating the processors into groups is a useful paradigm for programming an amorphous computer because groups can be used for specialization, increased robustness, and efficient resource allocation. This paper presents a new algorithm, called the clubs algorithm, for efficiently aggregating processors into groups in an amorphous computer, in time proportional to the local density of processors. The clubs algorithm is well-suited to the unique characteristics of an amorphous computer. In addition, the algorithm derives two properties from the physical embedding of the amorphous computer: an upper bound on the number of groups formed and a constant upper bound on the density of groups. The clubs algorithm can also be extended to find the maximal independent set (MIS) and $Delta + 1$ vertex coloring in an amorphous computer in $O(log N)$ rounds, where $N$ is the total number of elements and $Delta$ is the maximum degree.

Coordinate-Independent Computations on Differential Equations

This project investigates the computational representation of differentiable manifolds, with the primary goal of solving partial differential equations using multiple coordinate systems on general n- dimensional spaces. In the process, this abstraction is used to perform accurate integrations of ordinary differential equations using multiple coordinate systems. In the case of linear partial differential equations, however, unexpected difficulties arise even with the simplest equations.

Separating Reflections from Images Using Independent Components Analysis

The image of an object can vary dramatically depending on lighting, specularities/reflections and shadows. It is often advantageous to separate these incidental variations from the intrinsic aspects of an image. Along these lines this paper describes a method for photographing objects behind glass and digitally removing the reflections off the glass leaving the image of the objects behind the glass intact. We describe the details of this method which employs simple optical techniques and independent components analysis (ICA) and show its efficacy with several examples.

The impact of interconnectedness in a triadic relationship between a financial services provider, IFAs, and customers.

The aim of this study is to investigate the impact of interconnectedness between a long-term savings and investments provider, Independent Financial Advisers (IFAs) and customers. Ritter’s (2000) framework of the effect of interconnectedness was used to analyse this triadic relationship. Conceptual studies of triadic business relationships are scarce in marketing and organisational research (Blakenburg & Johanson, 1992; Havila, Johnson & Thilenius, 2004; Ritter, 2000). However, the applicability of a triadic relationship has been tested in a number of case studies (Andersson & Mattsson, 2004; Cunningham & Pyatt, 1989; Jaaskelainen, Kuivalainen & Saarenketo, 2000; Narayandas, 2002; Odorici & Corrado, 2004; Pardo & Salle, 1994; Trimachi, 2002). This study was conducted in collaboration with one of the UK’s largest long-term savings and investments providers. A substantial proportion of the provider’s business is conducted through IFAs and thus their significance as a major stakeholder. Indeed, the majority of sales in the long-term savings and investments industry in the UK are realised through IFAs. Academic studies (Gough, 2005; Gough & Nurullah, 2009) have indicated that IFAs are the strongest distribution channel in the industry. Thus, by analysing the impact of the interconnectedness in this relationship, a strategy that can increase the relationship performance can be proposed. However, to the best of the authors’ knowledge, a study that investigates the effect of the interconnectedness in this triadic relationship has not been established. In addition, the regulatory environment which continues to face change such as the recent implementation of Retail Distribution Review (RDR) on 1st January 2013 will make the relationship more rather than less complex.

Jurisdiction and the Internet: Regulatory Competence over Online Activity

null RAE2008

The performance of models relating species geographical distributions to climate is independent of trophic level

Brian Huntley, Rhys E. Green, Yvonne C. Collingham, Jane K. Hill, Stephen G. Willis , Patrick J. Bartlein, Wolfgang Cramer, Ward J. M. Hagemeijer and Christopher J. Thomas (2004). The performance of models relating species geographical distributions to climate is independent of trophic level. Ecology Letters, 7(5), 417-426. Sponsorship: NERC (awards: GR9/3016, GR9/04270, GR3/12542, NER/F/S/2000/00166) / RSPB RAE2008

Age- and activity-related differences in the abundance of Myosin essential and regulatory light chains in human muscle

Traditional methods for phenotyping skeletal muscle (e.g., immunohistochemistry) are labor-intensive and ill-suited to multixplex analysis, i.e., assays must be performed in a series. Addressing these concerns represents a largely unmet research need but more comprehensive parallel analysis of myofibrillar proteins could advance knowledge regarding age- and activity-dependent changes in human muscle. We report a label-free, semi-automated and time efficient LC-MS proteomic workflow for phenotyping the myofibrillar proteome. Application of this workflow in old and young as well as trained and untrained human skeletal muscle yielded several novel observations that were subsequently verified by multiple reaction monitoring (MRM).We report novel data demonstrating that human ageing is associated with lesser myosin light chain 1 content and greater myosin light chain 3 content, consistent with an age-related reduction in type II muscle fibers. We also disambiguate conflicting data regarding myosin regulatory light chain, revealing that age-related changes in this protein more closely reflect physical activity status than ageing per se. This finding reinforces the need to control for physical activity levels when investigating the natural process of ageing. Taken together, our data confirm and extend knowledge regarding age- and activity-related phenotypes. In addition, the MRM transitions described here provide a methodological platform that can be fine-tuned to suite multiple research needs and thus advance myofibrillar phenotyping.

Deterministic Computations Whose History Is Independent of the Order of Asynchronous Updating

Consider a network of processors (sites) in which each site x has a finite set N(x) of neighbors. There is a transition function f that for each site x computes the next state ξ(x) from the states in N(x). But these transitions (updates) are applied in arbitrary order, one or many at a time. If the state of site x at time t is η(x; t) then let us define the sequence ζ(x; 0); ζ(x; 1), ... by taking the sequence η(x; 0),η(x; 1), ... , and deleting each repetition, i.e. each element equal to the preceding one. The function f is said to have invariant histories if the sequence ζ(x; i), (while it lasts, in case it is finite) depends only on the initial configuration, not on the order of updates. This paper shows that though the invariant history property is typically undecidable, there is a useful simple sufficient condition, called commutativity: For any configuration, for any pair x; y of neighbors, if the updating would change both ξ(x) and ξ(y) then the result of updating first x and then y is the same as the result of doing this in the reverse order. This fact is derivable from known results on the confluence of term-rewriting systems but the self-contained proof given here may be justifiable.

An Independent-Connection Model for Traffic Matrices

A common assumption made in traffic matrix (TM) modeling and estimation is independence of a packet's network ingress and egress. We argue that in real IP networks, this assumption should not and does not hold. The fact that most traffic consists of two-way exchanges of packets means that traffic streams flowing in opposite directions at any point in the network are not independent. In this paper we propose a model for traffic matrices based on independence of connections rather than packets. We argue that the independent connection (IC) model is more intuitive, and has a more direct connection to underlying network phenomena than the gravity model. To validate the IC model, we show that it fits real data better than the gravity model and that it works well as a prior in the TM estimation problem. We study the model's parameters empirically and identify useful stability properties. This justifies the use of the simpler versions of the model for TM applications. To illustrate the utility of the model we focus on two such applications: synthetic TM generation and TM estimation. To the best of our knowledge this is the first traffic matrix model that incorporates properties of bidirectional traffic.

Molecular analysis of virulence mechanisms associated with adherent-invasive Escherichia coli (AIEC)

Crohn's Disease (CD) is a chronic inflammatory bowel disease of unknown etiology. Recent work has shown that a new pathotype of Escherichia coli, Adherent Invasive E. coli (AIEC) may be associated with CD. AIEC has been shown to adhere to and invade epithelial cells and to replicate within macrophages (together this is called the AIEC phenotype). In this thesis, the AIEC phenotype of 84 E. coli strains were determined in order to identify the prevalence of this phenotype within the E. coli genus. This study showed that a significant proportion of E. coli strains (approx. 5%) are capable of adhering to and invading epithelial cells and undergoing intramacrophage replication. Moreover, the results presented in this study indicate a correlation between survival in macrophage and resistance to grazing by amoeba supporting the coincidental evolution hypothesis that resistance to amoebae could be a driving force in the evolution of pathogenicity in some bacteria, such as AIEC. In addition, this study has identified an important regulatory role for the CpxA/R two component system (TCS) in the invasive abilities of AIEC HM605, a colonic mucosa-associated CD isolate. A mutation in cpxR was shown to be defective in the invasion of epithelial cells and this defect was shown to be independent of motility or the expression of Type 1 fimbriae, factors that have been shown to be involved in the invasion of another strain of AIEC, isolated from a patient with ileal CD, called LF82. The CpxA/R TCS responds to disturbances in the cell envelope and has been implicated in the virulence of a number of Gram negative pathogens. In this study it is shown that the CpxA/R TCS regulates the expression of a potentially novel invasin called SinH. SinH is found in a number of invasive strains of E. coli and Salmonella. Moreover work presented here shows that a critical mechanism underpinning AIEC persistence in macrophages is the repair of DNA bases damaged by macrophage oxidants. Together these findings provide evidence to suggest that AIEC are a diverse group of E. coli and possess diverse molecular mechanisms and virulence factors that contribute to the AIEC phenotype. In addition, AIEC may have gone through different evolutionary histories acquiring various molecular mechanisms ultimately culminating in the AIEC phenotype. The gastrointestinal (GI) tract harbors a diverse microbiota; most are symbiotic or commensal however some bacteria have the potential to cause disease (pathobiont). The work presented here provides evidence to support the model that AIEC are pathobionts. AIEC strains can be carried as commensals in healthy guts however, when the intestinal homeostasis is disrupted, such as in the compromised gut of CD patients, AIEC may behave as opportunistic pathogens and cause and/or contribute to disease by driving intestinal inflammation.

Training in and assessment of the procedural skills required to perform peripheral nerve blockade

The training and ongoing education of medical practitioners has undergone major changes in an incremental fashion over the past 15 years. These changes have been driven by patient safety, educational, economic and legislative/regulatory factors. In the near future, training in procedural skills will undergo a paradigm shift to proficiency based progression with associated requirements for competence-based programmes, valid, reliable assessment tools and simulation technology. Before training begins, the learning outcomes require clear definition; any form of assessment applied should include measurement of these outcomes. Currently training in a procedural skill often takes place on an ad hoc basis. The number of attempts necessary to attain a defined degree of proficiency varies from procedure to procedure. Convincing evidence exists that simulation training helps trainees to acquire skills more efficiently rather than relying on opportunities in their clinical practice. Simulation provides a safe, stress free environment for trainees for skill acquisition, generalization and transfer via deliberate practice. The work described in this thesis contributes to a greater understanding of how medical procedures can be performed more safely and effectively through education. The effect of feedback, provided to novices in a standardized setting on a bench model, based on knowledge of performance was associated with an increase in the speed of skill acquisition and a decrease in error rate during initial learning. The timing of feedback was also associated with effective learning of skill. A marked attrition of skills (independent of the type of feedback provided) was demonstrable 24 hrs after they have first been learned. Using the principles of feedback as described above, when studying the effect of an intense training program on novices of varied years of experience in anaesthesia (i.e. the present training programmes / courses of an intense training day for one or more procedures). There was a marked attrition of skill at 24 hours with a significant correlation with increasing years of experience; there also appeared to be an inverse relationship between years of experience in anaesthesia and performance. The greater the number of years of practice experience, the longer it required a learner to acquire a new skill. The findings of the studies described in this thesis may have important implications for the trainers, trainees and training bodies in the design and implementation of training courses and the formats of delivery of changing curricula. Both curricula and training modalities will need to take account of characteristics of individual learners and the dynamic nature of procedural healthcare.

Multi-parametric metabolic assessment of cells under stress conditions

Glycolysis, glutaminolysis, the Krebs cycle and oxidative phosphorylation are the main metabolic pathways. Exposing cells to key metabolic substrates (glucose, glutamine and pyruvate); investigation of the contribution of substrates in stress conditions such as uncoupling and hypoxia was conducted. Glycolysis, O2 consumption, O2 and ATP levels and hypoxia inducible factor (HIF) signalling in PC12 cells were investigated. Upon uncoupling with FCCP mitochondria were depolarised similarly in all cases, but a strong increase in respiration was only seen in the cells fed on glutamine with either glucose or pyruvate. Inhibition of glutaminolysis reversed the glutamine dependant effect. Differential regulation of the respiratory response to FCCP by metabolic environment suggests mitochondrial uncoupling has a potential for substrate-specific inhibition of cell function. At reduced O2 availability (4 % and 0 % O2), cell bioenergetics and local oxygenation varied depending on the substrate composition. Results indicate that both supply and utilisation of key metabolic substrates can affect the pattern of HIF-1/2α accumulation by differentially regulating iO2¬, ATP levels and Akt/Erk/AMPK pathways. Inhibition of key metabolic pathways can modulate HIF regulatory pathways, metabolic responses and survival of cancer cells in hypoxia. Hypoxia leads to transcriptional activation, by HIF, of pyruvate dehydrogenase (PDH) kinase which phosphorylates and inhibits PDH, a mitochondrial enzyme that converts pyruvate into acetyl-CoA. The levels of PDH (total and phosphorylated), PDH kinase and HIF-1α were analysed in HCT116 and HCT116 SCO2-/- (deficient in complex IV of the respiratory chain) grown under 20.9 % and 3 % O2. Data indicate that regulation of PDH can occur in a manner independent of the HIF-1/PDH kinase 1 axis, mitochondrial respiration and the demand for acetyl-CoA. Collectively these results can be applied to many diseases; reduced nutrient supply and O2 during ischemia/stroke, hypoglycaemia in diabetes mellitus and cancer associated changes in uncoupling protein expression levels.

Anti-CTLA-4 treatment induces IL-10-producing ICOS+ regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis.

BACKGROUND AND AIMS: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to act as a negative regulator of T cell function and has been implicated in the regulation of T helper 1 (Th1)/Th2 development and the function of regulatory T cells. Tests were carried out to determine whether anti-CTLA-4 treatment would alter the polarisation of naive T cells in vivo. METHODS: Mice were treated with anti-CTLA-4 monoclonal antibody (mAb) (UC10-4F10) at the time of immunisation or colonic instillation of trinitrobenzene sulfonic acid (TNBS). The cytokines produced by lymph node cells after in vitro antigenic stimulation and the role of indoleamine 2,3 dioxygenase (IDO) and of interleukin-10 (IL-10) were tested, and the survival of mice was monitored. RESULTS: Injection of anti-CTLA-4 mAb in mice during priming induced the development of adaptive CD4(+) regulatory T cells which expressed high levels of ICOS (inducible co-stimulator), secreted IL-4 and IL-10. This treatment inhibited Th1 memory responses in vivo and repressed experimental intestinal inflammation. The anti-CTLA-4-induced amelioration of disease correlated with IDO expression and infiltration of ICOS(high) Foxp3(+) T cells in the intestine, suggesting that anti-CTLA-4 acted indirectly through the development of regulatory T cells producing IL-10 and inducing IDO. CONCLUSIONS: These observations emphasise the synergy between IL-10 and IDO as anti-inflammatory agents and highlight anti-CTLA-4 treatment as a potential novel immunotherapeutic approach for inducing adaptive regulatory T cells.