TLR2, but Not TLR4, is required for effective host defence against Chlamydia respiratory tract infection in early life

Chlamydia pneumoniae commonly causes respiratory tract infections in children, and epidemiological investigations strongly link infection to the pathogenesis of asthma. The immune system in early life is immature and may not respond appropriately to pathogens. Toll-like receptor (TLR)2 and 4 are regarded as the primary pattern recognition receptors that sense bacteria, however their contribution to innate and adaptive immunity in early life remains poorly defined. We investigated the role of TLR2 and 4 in the induction of immune responses to Chlamydia muridarum respiratory infection, in neonatal wild-type (Wt) or TLR2-deficient (−/−), 4−/− or 2/4−/− BALB/c mice. Wt mice had moderate disease and infection. TLR2−/− mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4−/− mice were asymptomatic. TLR2/4−/− mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4−/− mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4+ and CD8+ T-cells into the lungs. Wt mice also had effective production of interferon (IFN)γ in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2−/− mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFNγ responses and T-cell proliferation were reduced. TLR2/4−/− mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases.

Recognising team activities from noisy data

Recently, vision-based systems have been deployed in professional sports to track the ball and players to enhance analysis of matches. Due to their unobtrusive nature, vision-based approaches are preferred to wearable sensors (e.g. GPS or RFID sensors) as it does not require players or balls to be instrumented prior to matches. Unfortunately, in continuous team sports where players need to be tracked continuously over long-periods of time (e.g. 35 minutes in field-hockey or 45 minutes in soccer), current vision-based tracking approaches are not reliable enough to provide fully automatic solutions. As such, human intervention is required to fix-up missed or false detections. However, in instances where a human can not intervene due to the sheer amount of data being generated - this data can not be used due to the missing/noisy data. In this paper, we investigate two representations based on raw player detections (and not tracking) which are immune to missed and false detections. Specifically, we show that both team occupancy maps and centroids can be used to detect team activities, while the occupancy maps can be used to retrieve specific team activities. An evaluation on over 8 hours of field hockey data captured at a recent international tournament demonstrates the validity of the proposed approach.

Scene invariant multi camera crowd counting

Automated crowd counting has become an active field of computer vision research in recent years. Existing approaches are scene-specific, as they are designed to operate in the single camera viewpoint that was used to train the system. Real world camera networks often span multiple viewpoints within a facility, including many regions of overlap. This paper proposes a novel scene invariant crowd counting algorithm that is designed to operate across multiple cameras. The approach uses camera calibration to normalise features between viewpoints and to compensate for regions of overlap. This compensation is performed by constructing an 'overlap map' which provides a measure of how much an object at one location is visible within other viewpoints. An investigation into the suitability of various feature types and regression models for scene invariant crowd counting is also conducted. The features investigated include object size, shape, edges and keypoints. The regression models evaluated include neural networks, K-nearest neighbours, linear and Gaussian process regresion. Our experiments demonstrate that accurate crowd counting was achieved across seven benchmark datasets, with optimal performance observed when all features were used and when Gaussian process regression was used. The combination of scene invariance and multi camera crowd counting is evaluated by training the system on footage obtained from the QUT camera network and testing it on three cameras from the PETS 2009 database. Highly accurate crowd counting was observed with a mean relative error of less than 10%. Our approach enables a pre-trained system to be deployed on a new environment without any additional training, bringing the field one step closer toward a 'plug and play' system.

Rank minimization across appearance and shape for AAM ensemble fitting

Active Appearance Models (AAMs) employ a paradigm of inverting a synthesis model of how an object can vary in terms of shape and appearance. As a result, the ability of AAMs to register an unseen object image is intrinsically linked to two factors. First, how well the synthesis model can reconstruct the object image. Second, the degrees of freedom in the model. Fewer degrees of freedom yield a higher likelihood of good fitting performance. In this paper we look at how these seemingly contrasting factors can complement one another for the problem of AAM fitting of an ensemble of images stemming from a constrained set (e.g. an ensemble of face images of the same person).

Soundage : a practice-led approach to Gertrude Stein, sound, and generative language

In this practice-led research project I work to show how a re-reading and a particular form of listening to the sound-riddled nature of Gertrude Stein's work, Two: Gertrude Stein and her Brother, presents us with a contemporary theory of sound in language. This theory, though in its infancy, is a particular enjambment of sounded language that presents itself as an event, engaged with meaning, with its own inherent voice. It displays a propensity through engagement with the 'other' to erupt into love. In this thesis these qualities are reverberated further through the work of Seth Kim-Cohen's notion of the non-cochlear, Simon Jarvis's notion of musical thinking, Jean-Jacques Lecercle's notion of délire or nonsense, Luce Irigaray's notion of jouissant love and the Bracha Ettinger's notion of the generative matrixial border space. This reading then is simultaneously paired with my own work of scoring and creating a digital opera from Stein's work, thereby testing and performing Stein's theory. In this I show how a re-reading and relistening to Stein's work can be significant to feminist ethical language frames, contemporary philosophy, sonic art theory and digital language frames. Further significance of this study is that when the reverberation of Stein's engagements with language through sound can be listened to, a pattern emerges, one that encouragingly problematizes subjectivity and interweaves genres/methods and means, creating a new frame for sound in language, one with its own voice that I call soundage.

Natural, engineered and synthetic inhibitors of kallikrein-related peptidases

There is a rapidly growing appreciation of the important physiological roles played by kallikreins and kallikrein-related peptidases (KLKs). Recent studies have revealed that these enzymes control key events in processes as diverse as inflammation and skin desquamation. Accordingly, there is considerable interest in developing tools to further dissect kallikrein activity, and a burgeoning effort aimed at producing lead inhibitors for therapeutic development. Indeed, several candidate inhibitors are already in clinical trials. This chapter surveys the naturally occurring kallikrein inhibitors, together with strategies for employing these molecules as bioscaffolds, as well as current progress in the development of small-molecule kallikrein inhibitors.

In the shadow of the enlightenment : Le Corbusier, Le Faisceau and Georges Valois

On 9 January 1927 Le Corbusier materialised on the front cover of the Faisceau journal edited by Georges Valois Le Nouveau Siècle which printed the single-point perspective of Le Corbusier’s Plan Voisin and an extract from the architect’s discourse in Urbanisme. In May Le Corbusier presented slides of his urban designs at a fascist rally. These facts have been known ever since the late 1980s when studies emerged in art history that situated Le Corbusier’s philosophy in relation to the birth of twentieth-century fascism in France—an elision in the dominant reading of Le Corbusier’s philosophy, as a project of social utopianism, whose received genealogy is Saint-Simon and Charles Fourier. Le Corbusier participated with the first group in France to call itself fascist, Valois’s militant Faisceau des Combattants et Producteurs, the “Blue Shirts,” inspired by the Italian “Fasci” of Mussolini. Thanks to Mark Antliff, we know the Faisceau did not misappropriate Le Corbusier’s plans, in some remote quasi-symbolic sense, rather Valois’s organisation was premised on the redesign of Paris based on Le Corbusier’s schematic designs. Le Corbusier’s Urbanisme was considered the “prodigious” model for the fascist state Valois called La Cité Française – after his mentor the anarcho-syndicalist Georges Sorel. Valois stated that Le Corbusier’s architectural concepts were “an expression of our profoundest thoughts,” the Faisceau, who “saw their own thought materialized” on the pages of Le Corbusier’s plans. The question I pose is, In what sense is Le Corbusier’s plan a complete representation of La Cité? For Valois, the fascist city “represents the collective will of La Cité” invoking Enlightenment philosophy, operative in Sorel, namely Rousseau, for whom the notion of “collective will” is linked to the idea of political representation: to ‘stand in’ for someone or a group of subjects i.e. the majority vote. The figures in Voisin are not empty abstractions but the result of “the will” of the “combatant-producers” who build the town. Yet, the paradox in anarcho-syndicalist anti-enlightenment thought – and one that became a problem for Le Corbusier – is precisely that of authority and representation. In Le Corbusier’s plan, the “morality of the producers” and “the master” (the transcendent authority that hovers above La Cité) is lattened into a single picture plane, thereby abolishing representation. I argue that La Cité pushed to the limits of formal abstraction by Le Corbusier thereby reverts to the Enlightenment myth it first opposed, what Theodor Adorno would call the dialectic of enlightenment.

A transcription factor map as revealed by a genome-wide gene expression analysis of whole-blood mRNA transcriptome in multiple sclerosis

Background Several lines of evidence suggests that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but a complete mapping the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors which may be involved in one subtype may not be in others. We investigated the possibility that this network could be mapped using microarray technologies and modern bioinformatics methods on a dataset from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls, Methodology/Principal Findings We have used two different analytical methodologies: a differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that seem to be statistically overrepresented in genes which are either differentially expressed (or differentially co-expressed) in cases and controls (e.g. V$KROX_Q6, p-value < 3.31E-6; V$CREBP1_Q2, p-value < 9.93E-6, V$YY1_02, p-value < 1.65E-5). Conclusions/significance: Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. Analysing the published literature we have found that these transcription factors are involved in the early T-lymphocyte specification and commitment as well as in oligodendrocytes dedifferentiation and development. The most significant transcription factors motifs were for the Early Growth response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families.

HLA-DRB1 associations with disease susceptibility and clinical course in Australians with multiple sclerosis

Human leucocyte antigen (HLA)-DRB1*1501 and other class II alleles influence susceptibility to multiple sclerosis (MS), but their contribution if any to the clinical course of MS remains uncertain. Here, we have investigated DRB1 alleles in a large sample of 1230 Australian MS cases, with some enrichment for subjects with primary progressive (PPMS) disease (n = 246) and 1210 healthy controls. Using logistic regression, we found that DRB1*1501 was strongly associated with risk (P = 7 x 10-45), as expected, and after adjusting for DRB1*1501, a predisposing effect was also observed for DRB1*03 (P = 5 x 10-7). Individuals homozygous for either DRB1*15 or DRB1*03 were considerably more at risk of MS than heterozygotes and non-carriers. Both the DRB1*04 and the DRB1*01/DRB1*15 genotype combination, respectively, protected against PPMS in comparison to subjects with relapsing disease. Together, these data provide further evidence of heterogeneity at the DRB1 locus and confirm the importance of HLA variants in the phenotypic expression of MS.

Why are pedestrian crashes so different in developing countries? A review of relevant factors in relation to their impact in Ethiopia

Much is known about pedestrian behaviour and crash risk in developed countries. In contrast, the literature on pedestrian crash risk in developing countries reveals wide gaps in knowledge and understanding, and a comprehensive assessment is lacking. In particular, pedestrian behaviour in developing countries is fundamentally different in comparison to developed countries, and is influenced by a variety of less well understood contributing factors, leading to difficulty in modelling and predicting pedestrian crash risk and in turn identifying effective safety countermeasures. This paper provides a comprehensive synthesis of the factors known to influence pedestrian crash risk in developing countries, then focuses on Ethiopia as a specific example. The paper identifies where critical gaps in knowledge exist regarding pedestrian crash risk and associated behaviour in developing countries--a set of knowledge gaps which collectively are significant. The paper concludes by articulating a critical research path moving forward, with the aim to achieve an improved understanding of developing country pedestrian crash risk, and an ultimate goal of identifying effective pedestrian safety countermeasures suited to the unique challenges faced by transport system managers in developing countries.

Non-covalent surface modification of boron nitride nanotubes for enhanced catalysis

Boron nitride nanotubes were functionalized by microperoxidase-11 in aqueous media, showing improved catalytic performance due to a strong electron coupling 10 between the active centre of microperoxidase-11 and boron nitride nanotubes. One main application challenge of enzymes as biocatalysts is molecular aggregation in the aqueous solution. This issue is addressed by immobilization of enzymes on solid supports which 15 can enhance enzyme stability and facilitate separation, and recovery for reuse while maintaining catalytic activity and selectivity. The protein-nanoparticle interactions play a key role in bio-nanotechnology and emerge with the development of nanoparticle-protein “corona”. Bio-molecular coronas provide a 20 unique biological identity of nanosized materials.1, 2 As a structural analogue to carbon nanotubes (CNTs), Boron nitride nanotubes have boron and nitrogen atoms distributed equally in hexagonal rings and exhibit excellent mechanical strength, unique physical properties, and chemical stability at high-temperatures. 25 The chemical inertness of BN materials suits to work in hazardous environments, making them an optimal candidate in practical applications in biological and medical field.3, 4

Sleepiness : how a biological drive can influence other risky road user behaviours

The Safe System approach to road safety utilises a holistic view of the interactions among vehicles, roads and road users. Yet, the contribution of each of these factors to crashes is vastly different. The role of road users is widely acknowledged as an overwhelming contributor to road crashes. Substantial gains have been made with improvements to vehicle and roads over a number of years. However, improvements of the road user’s behaviour has been (in some cases) less substantial. A road user behaviour that is relatively unregulated is driver sleepiness, which is part of the ‘fatal five’ of risky road user behaviours. The effect of sleepiness is ubiquitous – sleepiness is a state that most, if not all drivers on our roads has experienced, and is habitually exposed to. The quality and quantity of daily sleep is integral to our level of neurobehavioural performance during wakefulness and as such can have a compounding effect on a number of other risky driving behaviours. This paper will discuss the potential influence of sleepiness as an interceding factor for a number of risky driving behaviours. Little effort has been given to increasing awareness of the deleterious and wide ranging effects that sleepiness has on road safety. Given the wide ranging influence of sleepiness, improvements of ‘sleep health’ as a protective factor at the community or individual level could lead to significant reductions in road trauma and increases of general well being. A discussion of potential actions to reduce sleepiness is required if reductions of road trauma are to continue.

Characteristics of police-reported road traffic crashes in Ethiopia over a six year period

Ethiopia has one of Africa’s fastest growing non-oil producing economies and an increasing level of motorisation (AfDB, OECD, UNDP, & UNECA, 2012). This rapidly increasing mobility has created some unique road safety concerns; however there is scant published information and related commentary (United Nations Economic Commission for Africa, 2009). The objective of this paper is to quantify police-reported traffic crashes in Ethiopia and characterise the existing state of road safety. Six years (July 2005 - June 2011) of police-reported crash data were analysed, consisting of 12,140 fatal and 29,454 injury crashes on the country’s road network. The 12,140 fatal crashes involved 1,070 drivers, 5,702 passengers, and 7,770 pedestrians, totalling 14,542 fatalities, an average of 1.2 road user fatalities per crash. An important and glaring trend that emerges is that more than half of the fatalities in Ethiopia involve pedestrians. The majority of the crashes occur during daytime hours, involve males, and involve persons in the 18-50 age group—Ethiopia’s active workforce. Crashes frequently occur in mid blocks or roadways. The predominant collision between motor vehicles and pedestrians was a rollover on a road tangent section. Failing to observe the priority of pedestrians and speeding were the major causes of crashes attributed by police. Trucks and minibus taxis were involved in the majority of crashes, while automobiles (small vehicles) were less involved in crashes relative to other vehicle types, partially because small vehicles tend to be driven fewer kilometres per annum. These data illustrate and justify a high priority to identify and implement effective programs, policies, and countermeasures focused on reducing pedestrian crashes.

Effects of mobile phone distraction on drivers’ reaction times

Distraction resulting from mobile phone use whilst driving has been shown to increase the reaction times of drivers, thereby increasing the likelihood of a crash. This study compares the effects of mobile phone conversations on reaction times of drivers responding to traffic events that occur at different points in a driver’s field of view. The CARRS-Q Advanced Driving Simulator was used to test a group of young drivers on various simulated driving tasks including a traffic event that occurred within the driver’s central vision—a lead vehicle braking suddenly—and an event that occurred within the driver’s peripheral—a pedestrian entering a zebra crossing from a footpath. Thirty-two licensed drivers drove the simulator in three phone conditions: baseline (no phone conversation), and while engaged in hands-free and handheld phone conversations. The drivers were aged between 21 to 26 years and split evenly by gender. Differences in reaction times for an event in a driver’s central vision were not statistically significant across phone conditions, probably due to a lower speed selection by the distracted drivers. In contrast, the reaction times to detect an event that originated in a distracted driver’s peripheral vision were more than 50% longer compared to the baseline condition. A further statistical analysis revealed that deterioration of reaction times to an event in the peripheral vision was greatest for distracted drivers holding a provisional licence. Many critical events originate in a driver’s periphery, including vehicles, bicyclists, and pedestrians emerging from side streets. A reduction in the ability to detect these events while distracted presents a significant safety concern that must be addressed.

A parametric duration model of the reaction times of drivers distracted by mobile phone conversations

The use of mobile phones while driving is more prevalent among young drivers—a less experienced cohort with elevated crash risk. The objective of this study was to examine and better understand the reaction times of young drivers to a traffic event originating in their peripheral vision whilst engaged in a mobile phone conversation. The CARRS-Q Advanced Driving Simulator was used to test a sample of young drivers on various simulated driving tasks, including an event that originated within the driver’s peripheral vision, whereby a pedestrian enters a zebra crossing from a sidewalk. Thirty-two licensed drivers drove the simulator in three phone conditions: baseline (no phone conversation), hands-free and handheld. In addition to driving the simulator each participant completed questionnaires related to driver demographics, driving history, usage of mobile phones while driving, and general mobile phone usage history. The participants were 21 to 26 years old and split evenly by gender. Drivers’ reaction times to a pedestrian in the zebra crossing were modelled using a parametric accelerated failure time (AFT) duration model with a Weibull distribution. Also tested where two different model specifications to account for the structured heterogeneity arising from the repeated measures experimental design. The Weibull AFT model with gamma heterogeneity was found to be the best fitting model and identified four significant variables influencing the reaction times, including phone condition, driver’s age, license type (Provisional license holder or not), and self-reported frequency of usage of handheld phones while driving. The reaction times of drivers were more than 40% longer in the distracted condition compared to baseline (not distracted). Moreover, the impairment of reaction times due to mobile phone conversations was almost double for provisional compared to open license holders. A reduction in the ability to detect traffic events in the periphery whilst distracted presents a significant and measurable safety concern that will undoubtedly persist unless mitigated.