Evolution to a chronic disease niche correlates with increased sensitivity to tryptophan availability for the obligate intracellular bacterium Chlamydia pneumoniae

The chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer's disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host's immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more "susceptible" to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge.

Increased sensitivity to tryptophan bioavailability is a positive adaptation by the human strains of Chlamydia pneumoniae

One of the most significant activities induced by interferon-gamma against intracellular pathogens is the induction of IDO (indoleamine 2,3-dioxygenase) expression, which subsequently results in the depletion of tryptophan. We tested the hypothesis that human strains of Chlamydia pneumoniae are more sensitive to tryptophan limitation than animal C. pneumoniae strains. The human strains were significantly more sensitive to IFN-γ than the animal strains in a lung epithelia cell model (BEAS-2B), with exposure to 1 U ml(-1) IFN-γ resulting in complete loss of infectious yield of human strains, compared to the animal strains where reductions in infectious progeny were around 3.5-4.0 log. Strikingly, the IFN-γ induced loss of ability to form infectious progeny production was completely rescued by removal of the IFN-γ and addition of exogenous tryptophan for the human strains, but not the animal strains. In fact, a human heart strain was more capable of entering a non-infectious, viable persistent stage when exposed to IFN-γ and was also more effectively rescued, compared to a human respiratory strain. Exquisite susceptibility to IFN-γ, specifically due to tryptophan availability appears to be a core adaptation of the human C. pneumoniae strains, which may reflect the chronic nature of their infections in this host.

Blast response and sensitivity analysis of segmental tunnel

This research treated the response of underground transportation tunnels to surface blast loads using advanced computer simulation techniques. The influences of important parameters, such as tunnel material, geometrical configuration of segments and surrounding soil were investigated. The findings of this research offer significant new information on the blast performance of underground tunnels and will contribute towards future civil engineering applications.

Experimental study of load-bearing cold-formed steel walls exposed to realistic design fires

This paper presents the details of full scale fire tests of LSF wall panels conducted using realistic fire time-temperature curves. Tests included eight LSF wall specimens of various configurations exposed to both parametric design and natural fire curves. Details of the fire test set-up, test procedure and the results including the measured time-temperature and deformation curves of LSF wall panels are presented along with wall stud failure modes and times. This paper also compares the structural and thermal behavioural characteristics of LSF wall studs with those based on the standard time-temperature curve. Finally, the stud failure times and temperatures are summarized for both standard and realistic design fire curves. This study provides the necessary test data to validate the numerical models of LSF wall panels and to undertake a detailed study into the structural and thermal performance of LSF wall panels exposed to realistic design fire curves.

Development of realistic design fire time-temperature curves for the testing of cold-formed steel wall system

Fire resistance rating of light gauge steel frame (LSF) wall systems is obtained from fire tests based on the standard fire time-temperature curve. However, fire severity has increased in modern buildings due to higher fuel loads as a result of modern furniture and light weight constructions that make use of thermoplastics materials, synthetic foams and fabrics. Some of these materials are high in calorific values and increase both the spread of fire growth and heat release rate, thus increasing the fire severity beyond that of the standard fire curve. Further, the standard fire curve does not include a decay phase that is present in natural fires. Despite the increasing usage of LSF walls, their behaviour in real building fires is not fully understood. This paper presents the details of a research study aimed at developing realistic design fire curves for use in the fire tests of LSF walls. It includes a review of the characteristics of building fires, previously developed fire time-temperature curves, computer models and available parametric equations. The paper highlights that real building fire time-temperature curves depend on the fuel load representing the combustible building contents, ventilation openings and thermal properties of wall lining materials, and provides suitable values of many required parameters including fuel loads in residential buildings. Finally, realistic design fire time-temperature curves simulating the fire conditions in modern residential buildings are proposed for the testing of LSF walls.

Durability performance of carbon fibre-reinforced polymer strengthened circular hollow steel members under cold weather

The use of circular hollow steel members has attracted a great deal of attention during past few years because of having excellent structural properties, aesthetic appearance, corrosion and fire protection capability. However, no one can deny the structural deficiency of such structures due to reduction of strength when they are exposed to severe environmental conditions such as marine environment, cold and hot weather. Hence strengthening and retrofitting of structural steel members is now very imperative. This paper presents the findings of a research program that was conducted to study the bond durability of carbon fibre-reinforced polymer (CFRP) strengthened steel tubular members under cold weather and tested under four-point bending. Six number of CFRP-strengthened specimens and one unstrengthened specimen were considered in this program. The three specimens having sand blasted surface to be strengthened was pre-treated with MBrace primer and other three were remained untreated and then cured under ambient temperature at least four weeks and cold weather (3 C) for three and six months period of time. Quasi-static tests were then performed on beams to failure under four-point bending. The structural response of each specimen was predicted in terms of failure load, mid-span deflection, composite beam behaviour and failure mode. The research outcomes show that the cold weather immersion had an adverse effect on durability of CFRP-strengthened steel structures. Moreover, the epoxy based adhesion promoter was found to enhance the bond durability in plastic range. The analytical models presented in this study were found to be in good agreement in terms of predicting ultimate load and deflection. Finally, design factors are proposed to address the short-terms durability performance under cold weather.

A sensitivity analysis of train speed and its effect on railway capacity

Increasing train speeds is conceptually a simple and straight forward method to expand railway capacity, for example in comparison to other more extensive and elaborate alternatives. In this article an analytical capacity model has been investigated as a means of performing a sensitivity analysis of train speeds. The results of this sensitivity analysis can help improve the operation of this railway system and to help it cope with additional demands in the future. To test our approach a case study of the Rah Ahane Iran (RAI) national railway network has been selected. The absolute capacity levels for this railway network have been determined and the analysis shows that increasing trains speeds may not be entirely cost effective in all circumstances.

Unusually cold and dry winters increase mortality in Australia

Seasonal patterns in mortality have been recognised for decades, with a marked excess of deaths in winter, yet our understanding of the causes of this phenomenon is not yet complete. Research has shown that low and high temperatures are associated with increased mortality independently of season; however, the impact of unseasonal weather on mortality has been less studied. In this study, we aimed to determine if unseasonal patterns in weather were associated with unseasonal patterns in mortality. We obtained daily temperature, humidity and mortality data from 1988 to 2009 for five major Australian cities with a range of climates. We split the seasonal patterns in temperature, humidity and mortality into their stationary and non-stationary parts. A stationary seasonal pattern is consistent from year-to-year, and a non-stationary pattern varies from year-to-year. We used Poisson regression to investigate associations between unseasonal weather and an unusual number of deaths. We found that deaths rates in Australia were 20–30% higher in winter than summer. The seasonal pattern of mortality was non-stationary, with much larger peaks in some winters. Winters that were colder or drier than a typical winter had significantly increased death risks in most cities. Conversely summers that were warmer or more humid than average showed no increase in death risks. Better understanding the occurrence and cause of seasonal variations in mortality will help with disease prevention and save lives.

Cold water immersion enhances recovery of submaximal muscle function after resistance exercise

We investigated the effect of cold water immersion (CWI) on the recovery of muscle function and physiological responses following high-intensity resistance exercise. Using a randomized, cross-over design, 10 physically active men performed high-intensity resistance exercise, followed by one of two recovery interventions: 10 min of cold water immersion at 10°C, or 10 min active recovery (low-intensity cycling). After the recovery interventions, maximal muscle function was assessed after 2 h and 4 h by measuring jump height and isometric squat strength. Submaximal muscle function was assessed after 6 h by measuring the average load lifted during six sets of 10 squats at 80% 1RM. Intramuscular temperature (1 cm) was also recorded, and venous blood samples were analyzed for markers of metabolism, vasoconstriction and muscle damage. CWI did not enhance recovery of maximal muscle function. However, during the final three sets of the submaximal muscle function test, the participants lifted a greater load (p<0.05; 38%; Cohen’s d 1.3) following CWI compared with active recovery. During CWI, muscle temperature decreased 6°C below post-exercise values, and remained below pre-exercise values for another 35 min. Venous blood O2 saturation decreased below pre-exercise values for 1.5 h after CWI. Serum endothelin-1 concentration did not change after CWI, whereas it decreased after active recovery. Plasma myoglobin concentration was lower, whereas plasma interleukin-6 concentration was higher after CWI compared with active recovery. These results suggest that cold water immersion after resistance exercise allow athletes to complete more work during subsequent training sessions, which could enhance long-term training adaptations.

Anatomical specializations for enhanced olfactory sensitivity in kiwi, Apteryx mantelli

The ability to function in a nocturnal and ground-dwelling niche requires a unique set of sensory specializations. The New Zealand kiwi has shifted away from vision, instead relying on auditory and tactile stimuli to function in its environment and locate prey. Behavioral evidence suggests that kiwi also rely on their sense of smell, using olfactory cues in foraging and possibly also in communication and social interactions. Anatomical studies appear to support these observations: the olfactory bulbs and tubercles have been suggested to be large in the kiwi relative to other birds, although the extent of this enlargement is poorly understood. In this study, we examine the size of the olfactory bulbs in kiwi and compare them with 55 other bird species, including emus, ostriches, rheas, tinamous, and 2 extinct species of moa (Dinornithiformes). We also examine the cytoarchitecture of the olfactory bulbs and olfactory epithelium to determine if any neural specializations beyond size are present that would increase olfactory acuity. Kiwi were a clear outlier in our analysis, with olfactory bulbs that are proportionately larger than those of any other bird in this study. Emus, close relatives of the kiwi, also had a relative enlargement of the olfactory bulbs, possibly supporting a phylogenetic link to well-developed olfaction. The olfactory bulbs in kiwi are almost in direct contact with the olfactory epithelium, which is indeed well developed and complex, with olfactory receptor cells occupying a large percentage of the epithelium. The anatomy of the kiwi olfactory system supports an enhancement for olfactory sensitivities, which is undoubtedly associated with their unique nocturnal niche.

Accounting for management costs in sensitivity analyses of matrix population models

Traditional sensitivity and elasticity analyses of matrix population models have been used to inform management decisions, but they ignore the economic costs of manipulating vital rates. For example, the growth rate of a population is often most sensitive to changes in adult survival rate, but this does not mean that increasing that rate is the best option for managing the population because it may be much more expensive than other options. To explore how managers should optimize their manipulation of vital rates, we incorporated the cost of changing those rates into matrix population models. We derived analytic expressions for locations in parameter space where managers should shift between management of fecundity and survival, for the balance between fecundity and survival management at those boundaries, and for the allocation of management resources to sustain that optimal balance. For simple matrices, the optimal budget allocation can often be expressed as simple functions of vital rates and the relative costs of changing them. We applied our method to management of the Helmeted Honeyeater (Lichenostomus melanops cassidix; an endangered Australian bird) and the koala (Phascolarctos cinereus) as examples. Our method showed that cost-efficient management of the Helmeted Honeyeater should focus on increasing fecundity via nest protection, whereas optimal koala management should focus on manipulating both fecundity and survival simultaneously. These findings are contrary to the cost-negligent recommendations of elasticity analysis, which would suggest focusing on managing survival in both cases. A further investigation of Helmeted Honeyeater management options, based on an individual-based model incorporating density dependence, spatial structure, and environmental stochasticity, confirmed that fecundity management was the most cost-effective strategy. Our results demonstrate that decisions that ignore economic factors will reduce management efficiency. ©2006 Society for Conservation Biology.