Caspase-3-dependent phagocyte death during systemic Salmonella enterica serovar Typhimurium infection of mice.

Growth of Salmonella enterica in mammalian tissues results from continuous spread of bacteria to new host cells. Our previous work indicated that infective S. enterica are liberated from host cells via stochastic necrotic burst independently of intracellular bacterial numbers. Here we report that liver phagocytes can undergo apoptotic caspase-3-mediated cell death in vivo, with apoptosis being a rare event, more prevalent in heavily infected cells. The density-dependent apoptotic cell death is likely to constitute an alternative mechanism of bacterial spread as part of a bet-hedging strategy, ensuring an ongoing protective intracellular environment in which some bacteria can grow and persist.

The descriptive epidemiology of congenital and acquired cryptorchidism in a UK infant cohort.

INTRODUCTION: Recent studies in other European countries suggest that the prevalence of congenital cryptorchidism continues to increase. This study aimed to explore the prevalence and natural history of congenital cryptorchidism in a UK centre. METHODS: Between October 2001 and July 2008, 784 male infants were born in the prospective Cambridge Baby Growth Study. 742 infants were examined by trained research nurses at birth; testicular position was assessed using standard techniques. Follow-up assessments were completed at ages 3, 12, 18 and 24 months in 615, 462, 393 and 326 infants, respectively. RESULTS: The prevalence of cryptorchidism at birth was 5.9% (95% CI 4.4% to 7.9%). Congenital cryptorchidism was associated with earlier gestational age (p<0.001), lower birth weight (p<0.001), birth length (p<0.001) and shorter penile length at birth (p<0.0001) compared with other infants, but normal size after age 3 months. The prevalence of cryptorchidism declined to 2.4% at 3 months, but unexpectedly rose again to 6.7% at 12 months as a result of new cases. The cumulative incidence of "acquired cryptorchidism" by age 24 months was 7.0% and these cases had shorter penile length during infancy than other infants (p = 0.003). CONCLUSIONS: The prevalence of congenital cryptorchidism was higher than earlier estimates in UK populations. Furthermore, this study for the first time describes acquired cryptorchidism or "ascending testis" as a common entity in male infants, which is possibly associated with reduced early postnatal androgen activity.

Bacterial growth rate and host factors as determinants of intracellular bacterial distributions in systemic Salmonella enterica infections.

Bacteria of the species Salmonella enterica cause a range of life-threatening diseases in humans and animals worldwide. The within-host quantitative, spatial, and temporal dynamics of S. enterica interactions are key to understanding how immunity acts on these infections and how bacteria evade immune surveillance. In this study, we test hypotheses generated from mathematical models of in vivo dynamics of Salmonella infections with experimental observation of bacteria at the single-cell level in infected mouse organs to improve our understanding of the dynamic interactions between host and bacterial mechanisms that determine net growth rates of S. enterica within the host. We show that both bacterial and host factors determine the numerical distributions of bacteria within host cells and thus the level of dispersiveness of the infection.

Resistance of cast polyurethane elastomers to solid particle erosion

The rates of erosive wear have been measured for a series of eight polyester-based one-component castable polyurethane elastomers, with widely varying mechanical properties. Erosion tests were conducted with airborne silica sand, 120μm in particle size, at an impact velocity of 50 ms-1 and impact angles of 30° and 90°. For these materials, which all showed similar values of rebound resilience, the erosion rate increased with increasing hardness, tensile modulus and tensile strength. These findings are at variance with those expected for wear by abrasion, perhaps because of differences in the strain rate or strain levels imposed on the elastomer during erosion and abrasion.

Mode I crack growth resistance of metallic foams

A Dugdale-type cohesive zone model is used to predict the mode I crack growth resistance (R-curve) of metallic foams, with the fracture process characterized by an idealized traction-separation law that relates the crack surface traction to crack opening displacement. A quadratic yield function, involving the von Mises effective stress and mean stress, is used to account for the plastic compressibility of metallic foams. Finite element calculations are performed for the crack growth resistance under small scale yielding and small scale bridging in plane strain, with K-field boundary conditions. The following effects upon the fracture process are quantified: material hardening, bridging strength, T-stress (the non-singular stress acting parallel to the crack plane), and the shape of yield surface. To study the failure behaviour and notch sensitivity of metallic foams in the presence of large scale yielding, a study is made for panels embedded with either a centre-crack or an open hole and subjected to tensile stressing. For the centre-cracked panel, a transition crack size is predicted for which the fracture response switches from net section yielding to elastic-brittle fracture. Likewise, for a panel containing a centre-hole, a transition hole diameter exists for which the fracture response switches from net section yielding to a local maximum stress criterion at the edge of the hole.

Enhanced virulence of Salmonella enterica serovar typhimurium after passage through mice.

The interaction between Salmonella enterica and the host immune system is complex. The outcome of an infection is the result of a balance between the in vivo environment where the bacteria survive and grow and the regulation of fitness genes at a level sufficient for the bacteria to retain their characteristic rate of growth in a given host. Using bacteriological counts from tissue homogenates and fluorescence microscopy to determine the spread, localization, and distribution of S. enterica in the tissues, we show that, during a systemic infection, S. enterica adapts to the in vivo environment. The adaptation becomes a measurable phenotype when bacteria that have resided in a donor animal are introduced into a recipient naïve animal. This adaptation does not confer increased resistance to early host killing mechanisms but can be detected as an enhancement in the bacterial net growth rate later in the infection. The enhanced growth rate is lost upon a single passage in vitro, and it is therefore transient and not due to selection of mutants. The adapted bacteria on average reach higher intracellular numbers in individual infected cells and therefore have patterns of organ spread different from those of nonadapted bacteria. These experiments help in developing an understanding of the influence of passage in a host on the fitness and virulence of S. enterica.

Characterisation of cell adhesion to substrate materials and the resistance to enzymatic and mechanical cell-removal

Cell-implant adhesive strength is important for prostheses. In this paper, an investigation is described into the adhesion of bovine chondrocytes to Ti6Al4V-based substrates with different surface roughnesses and compositions. Cells were cultured for 2 or 5 days, to promote adhesion. The ease of cell removal was characterised, using both biochemical (trypsin) and mechanical (accelerated buoyancy and liquid flow) methods. Computational fluid dynamics (CFD) modelling has been used to estimate the shear forces applied to the cells by the liquid flow. A comparison is presented between the ease of cell detachment indicated using these methods, for the three surfaces investigated. © 2008 Materials Research Society.

Uplift resistance of buried pipelines at low cover-diameter ratios

Reliable estimates for the maximum available uplift resistance from the backfill soil are essential to prevent upheaval buckling of buried pipelines. The current design code DNV RP F110 does not offer guidance on how to predict the uplift resistance when the cover:pipe diameter (H/D) ratio is less than 2. Hence the current industry practice is to discount the shear contribution from uplift resitance for design scenarios with H/D ratios less than 1. The necessity of this extra conservatism is assessed through a series of full-scale and centrifuge tests, 21 in total, at the Schofield Centre, University of Cambridge. Backfill types include saturated loose sand, saturated dense sand and dry gravel. Data revealed that the Vertical Slip Surface Model remains applicable for design scenarios in loose sand, dense sand and gravel with H/D ratios less than 1, and that there is no evidence that the contribution from shear should be ignored at these low H/D ratios. For uplift events in gravel, the shear component seems reliable if the cover is more than 1-2 times the average particle size (D50), and more research effort is currenty being carried out to verify this conclusion. Strain analysis from the Particle Image Velocimetry (PIV) technique proves that the Vertical Slip Surface Model is a good representation of the true uplift deformation mechanism in loose sand at H/D ratios between 0.5 and 3.5. At very low H/D ratios (H/D < 0.5), the deformation mechanism is more wedge-like, but the increased contribution from soil weight is likely to be compensated by the reduced shear contributions. Hence the design equation based on the Vertical Slip Surface Model still produces good estimates for the maximum available uplift resistance. The evolution of shear strain field from PIV analysis provides useful insight into how uplift resistance is mobilized as the uplift event progresses. Copyright 2010, Offshore Technology Conference.

Uplift resistance of buried pipelines in blocky clay backfill

This paper presents the results from 10 minidrum centrifuge tests conducted at the Schofield Centre, compiled with 4 additional test results from Thusyanthan et al., 2008. All these tests were designed to measure the uplift resistance of a pipeline installed into stiff clay by trenching and backfilling, then uplifted approximately 3 months after installation. All tests were conducted at 1:30 scale using soil obtained from offshore clay samples. Experimental results show that clay blocks remained intact after 3 prototype months of consolidation, and were lifted rather than sheared during pipe pullout. The uplift resistance therefore depends on the weight of the soil cover and the shearing resistance mobilised at the softening contact points between the intact blocks and within the interstitial slurry. Slow drained pullout led to lower resistance than fast pullout, indicating that the drained response is critical for design. The varying scatter shows that peak uplift resistance is very sensitive to the arrangement of the backfill blocks when the cover and pipe diameter are comparable to the block size. Copyright © 2009 by The International Society of Offshore and Polar Engineers (ISOPE).

On the use of densification as a liquefaction resistance measure

The use of densification to improve the performance of shallow foundations during the centrifuge modeling of earthquake-induced liquefaction on level sand deposits is discussed. The densification of liquefiable ground provided protection against or significantly reduces liquefaction-related damage. Propagation of accelerations in the deposit exhibited considerable distinct features according to the relative density of the sand in the model. It was found that during the first couple of cycles, the dense soil amplifies the fundamental frequency component of the earthquake and preserves the higher frequency components.