Nonlinear diffusion and exclusion processes with contact interactions

Exclusion processes on a regular lattice are used to model many biological and physical systems at a discrete level. The average properties of an exclusion process may be described by a continuum model given by a partial differential equation. We combine a general class of contact interactions with an exclusion process. We determine that many different types of contact interactions at the agent-level always give rise to a nonlinear diffusion equation, with a vast variety of diffusion functions D(C). We find that these functions may be dependent on the chosen lattice and the defined neighborhood of the contact interactions. Mild to moderate contact interaction strength generally results in good agreement between discrete and continuum models, while strong interactions often show discrepancies between the two, particularly when D(C) takes on negative values. We present a measure to predict the goodness of fit between the discrete and continuous model, and thus the validity of the continuum description of a motile, contact-interacting population of agents. This work has implications for modeling cell motility and interpreting cell motility assays, giving the ability to incorporate biologically realistic cell-cell interactions and develop global measures of discrete microscopic data.

Forecasting negative effects of monotony and sensation seeking on performance during a vigilance task

The driving task requires sustained attention during prolonged periods, and can be performed in highly predictable or repetitive environments. Such conditions could create hypovigilance and impair performance towards critical events. Identifying such impairment in monotonous conditions has been a major subject of research, but no research to date has attempted to predict it in real-time. This pilot study aims to show that performance decrements due to monotonous tasks can be predicted through mathematical modelling taking into account sensation seeking levels. A short vigilance task sensitive to short periods of lapses of vigilance called Sustained Attention to Response Task is used to assess participants‟ performance. The framework for prediction developed on this task could be extended to a monotonous driving task. A Hidden Markov Model (HMM) is proposed to predict participants‟ lapses in alertness. Driver‟s vigilance evolution is modelled as a hidden state and is correlated to a surrogate measure: the participant‟s reactions time. This experiment shows that the monotony of the task can lead to an important decline in performance in less than five minutes. This impairment can be predicted four minutes in advance with an 86% accuracy using HMMs. This experiment showed that mathematical models such as HMM can efficiently predict hypovigilance through surrogate measures. The presented model could result in the development of an in-vehicle device that detects driver hypovigilance in advance and warn the driver accordingly, thus offering the potential to enhance road safety and prevent road crashes.

Molecular characterisation of six badnavirus species associated with leaf streak disease of banana in East Africa

Banana leaf streak disease, caused by several species of Banana streak virus (BSV), is widespread in East Africa. We surveyed for this disease in Uganda and Kenya, and used rolling-circle amplification (RCA) to detect the presence of BSV in banana. Six distinct badnavirus sequences, three from Uganda and three from Kenya, were amplified for which only partial sequences were previously available. The complete genomes were sequenced and characterised. The size and organisation of all six sequences was characteristic of other badnaviruses, including conserved functional domains present in the putative polyprotein encoded by open reading frame (ORF) 3. Based on nucleotide sequence analysis within the reverse transcriptase/ribonuclease H-coding region of open reading frame 3, we propose that these sequences be recognised as six new species and be designated as Banana streak UA virus, Banana streak UI virus, Banana streak UL virus, Banana streak UM virus, Banana streak CA virus and Banana streak IM virus. Using PCR and species-specific primers to test for the presence of integrated sequences, we demonstrated that sequences with high similarity to BSIMV only were present in several banana cultivars which had tested negative for episomal BSV sequences.

Selective accumulation of virus-specific CD8+ T cells within the peripheral blood stem cell compartment

The absence of cellular immunity is central to the pathogenesis of herpesvirus-mediated diseases after allogeneic hemopoietic stem cell transplantation (HSCT). For both bone marrow (BM)– and granulocyte-colony stimulating factor–mobilized peripheral blood stem cells (PBSCs) HSCT, donor-derived Epstein-Barr virus (EBV) and cytomegalovirus (CMV) peptide–specific CD8+ T cells clones undergo early expansion and persist long-term, with additional diversification arising from novel antigen-specific clones from donor-derived progenitors. Whether BM or PBSC is the superior source of antiviral CD8+ T cells is unclear. Given that PBSC has largely replaced BM as a source of stem cells for HSCT, it is unlikely that herpesvirus effector T-cell reconstitution will ever be compared prospectively. PBSC grafts contain 10 to 30 times more T cells than BM and a randomized study found proven viral infections were more frequent in BM than PBSC recipients, suggesting viral-specific T-cell immunity is enhanced in PBSC. Recently Moss showed in lung cancer patients that herpesvirus-specific BM-derived CD8+ T cells have unique homing properties relative to herpesvirus-specific CD8+ T cells present in unmobilized peripheral blood (PB). Immunodominant EBV-lytic peptide–specific CD8+ T cells were enriched in BM but were reduced for CMV peptide–specific CD8+ T cells relative to PB. EBV-latent peptide–specific CD8+ T cells were equivalent, which has relevance in the context of posttransplantation lymphoproliferative disorder for which impaired EBV-latent CD8+ T-cell immunity is a risk-factor. A comparison of herpesvirus-specific cellular immunity in PBSC versus PB has yet to be performed.

Development of a novel rolling-circle amplification technique to detect Banana streak virus which also discriminates between integrated and episomal virus sequences

Bananas are hosts to a large number of banana streak virus (BSV) species. However, diagnostic methods for BSV are inadequate because of the considerable genetic and serological diversity amongst BSV isolates and the presence of integrated BSV sequences in some banana cultivars which leads to false positives. In this study, a sequence non-specific, rolling-circle amplification (RCA) technique was developed and shown to overcome these limitations for the detection and subsequent characterisation of BSV isolates infecting banana. This technique was shown to discriminate between integrated and episomal BSV DNA, specifically detecting the latter in several banana cultivars known to contain episomal and/or integrated sequences of Banana streak Mysore virus (BSMyV), Banana streak OL virus (BSOLV) and Banana streak GF virus (BSGFV). Using RCA, the presence of BSMyV and BSOLV was confirmed in Australia, while BSOLV, BSGFV, Banana streak Uganda I virus (BSUgIV), Banana streak Uganda L virus (BSUgLV) and Banana streak Uganda M virus (BSUgMV) were detected in Uganda. This is the first confirmed report of episomally-derived BSUglV, BSUgLV and BSUgMV in Uganda. As well as its ability to detect BSV, RCA was shown to detect two other pararetroviruses, Sugarcane bacilliform virus in sugarcane and Cauliflower mosaic virus in turnip.

Organometallic macrocyclic chemistry. 8.(1) : an unusual metallacycle derived from phosphine−alkynyl thioether coupling

The α,ω-diyne 4,7,10-trithiatrideca-2,11-diyne reacts with [RuCl2(PPh3)3] and KPF6 to form the phosphonio-substituted metallatricyclic salt [RuCl(PPh3){κ4C,S,S′,S′′-S(C≡CMe)C2H4SC2H4SC(PPh3)CMe}]PF6 arising from the activation of one alkynyl group toward nucleophilic attack by extraneous phosphine.

Addressing childhood obesity through increased physical activity

Obesity is affecting an increasing proportion of children globally. Despite an appreciation that physical activity is essential for the normal growth and development of children and prevents obesity and obesity-related health problems, too few children are physically active. A concurrent problem is that today’s young people spend more time than previous generations did in sedentary pursuits, including watching television and engaging in screen-based games. Active behavior has been displaced by these inactive recreational choices, which has contributed to reductions in activity-related energy expenditure. Implementation of multifactorial solutions considered to offer the best chance of combating these trends is urgently required to redress the energy imbalance that characterizes obesity. The counterproductive ‘shame and blame’ mentality that apportions responsibility for the childhood obesity problem to sufferers, their parents, teachers or health-care providers needs to be changed. Instead, these groups should offer constant support and encouragement to promote appropriate physical activity in children. Failure to provide activity opportunities will increase the likelihood that the children of today will live less healthy (and possibly shorter)lives than their parents.

Estimation of parameters for macroparasite population evolution using approximate Bayesian computation

We estimate the parameters of a stochastic process model for a macroparasite population within a host using approximate Bayesian computation (ABC). The immunity of the host is an unobserved model variable and only mature macroparasites at sacrifice of the host are counted. With very limited data, process rates are inferred reasonably precisely. Modeling involves a three variable Markov process for which the observed data likelihood is computationally intractable. ABC methods are particularly useful when the likelihood is analytically or computationally intractable. The ABC algorithm we present is based on sequential Monte Carlo, is adaptive in nature, and overcomes some drawbacks of previous approaches to ABC. The algorithm is validated on a test example involving simulated data from an autologistic model before being used to infer parameters of the Markov process model for experimental data. The fitted model explains the observed extra-binomial variation in terms of a zero-one immunity variable, which has a short-lived presence in the host.

Corneal sensitivity as an ophthalmic marker of diabetic neuropathy

Purpose. The objective of this study was to explore the discriminative capacity of non-contact corneal esthesiometry (NCCE) when compared with the neuropathy disability score (NDS) score—a validated, standard method of diagnosing clinically significant diabetic neuropathy. Methods. Eighty-one participants with type 2 diabetes, no history of ocular disease, trauma, or surgery and no history of systemic disease that may affect the cornea were enrolled. Participants were ineligible if there was history of neuropathy due to non-diabetic cause or current diabetic foot ulcer or infection. Corneal sensitivity threshold was measured on the eye of dominant hand side at a distance of 10 mm from the center of the cornea using a stimulus duration of 0.9 s. The NDS was measured producing a score ranging from 0 to 10. To determine the optimal cutoff point of corneal sensitivity that identified the presence of neuropathy (diagnosed by NDS), the Youden index and “closest-to-(0,1)” criteria were used. Results. The receiver-operator characteristic curve for NCCE for the presence of neuropathy (NDS ≥3) had an area under the curve of 0.73 (p = 0.001) and, for the presence of moderate neuropathy (NDS ≥6), area of 0.71 (p = 0.003). By using the Youden index, for an NDS ≥3, the sensitivity of NCCE was 70% and specificity was 75%, and a corneal sensitivity threshold of 0.66 mbar or higher indicated the presence of neuropathy. When NDS ≥6 (indicating risk of foot ulceration) was applied, the sensitivity was 52% with a specificity of 85%. Conclusions. NCCE is a sensitive test for the diagnosis of minimal and more advanced diabetic neuropathy and may serve as a useful surrogate marker for diabetic and perhaps other neuropathies.