Three-dimensional analysis of reinforced concrete beam-column structures in fire

This is the author's accepted manuscript. The final published article is available from the link below. Published version copyright @ 2009 ASCE.In this paper a robust nonlinear finite-element procedure is developed for three-dimensional modeling of reinforced concrete beam-column structures in fire conditions. Because of the changes in material properties and the large deflections experienced in fire, both geometric and material nonlinearities are taken into account in this formulation. The cross section of the beam column is divided into a matrix of segments and each segment may have different material, temperature, and mechanical properties. The more complicated aspects of structural behavior in fire conditions, such as thermal expansion, transient state strains in the concrete, cracking or crushing of concrete, yielding of steel, and change in material properties with temperature are modeled. A void segment is developed to effectively model the effect of concrete spalling on the fire resistance of concrete beam-column members. The model developed can be used to quantify the residual strength of spalled reinforced concrete beam-column structures in fire. A series of comprehensive validations have been conducted to validate the model. From this research, it can be concluded that the influence of transient state strains of concrete on the deflection of structures can be very significant. However, there is very little effect on the failure time of a simple structural member. The impact of concrete spalling on both the thermal and structural behaviors of reinforced concrete members is very significant. It is vitally important to consider the prospect of concrete spalling in fire safety design for reinforced concrete buildings

A new design method for industrial portal frames in fire

For single-storey steel portal frames in fire, especially when they are situated close to a site perimeter, it is imperative that the boundary walls stay close to vertical, so that fires which occur are not allowed to spread to adjacent properties. A current UK fire design guide requires either that the whole frame be protected as a single element, or that the rafter may be left unprotected if column bases and foundations are designed to resist the forces and moments generated by rafter collapse, in order to ensure the lateral stability of the boundary walls. This can lead to very uneconomical foundation design and base-plate detailing. In previous studies carried out at the University of Sheffield it was found that a fundamental aspect of the collapse of a portal frame rafter is that it usually loses stability in a “snap-through” mechanism, but is capable of re-stabilising at high deflections, when the roof has inverted but the columns remain close to vertical. Numerical tests performed using the new model show that the strong base connections recommended by the current design method do not always lead to a conservative design. It is also found that initial collapse of the rafter is always caused by a plastic hinge mechanism based on the frame’s initial configuration. If the frame can then re-stabilize when the roof is substantially inverted, a second mechanism relying on the re-stabilized configuration can lead to failure of the whole frame. In this paper, a portal frame with different bases is simulated numerically using Vulcan, investigating the effect of different base strength on the collapse behaviour. The test results are compared with the failure mode assumed by the current design method. A new method for the estimation of re-stabilized positions of single-span frames in fire, using the second failure mechanism, is discussed and calibrated against the numerical test results

Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo

Endothelial cell survival is indispensable to maintain endothelial integrity and initiate new vessel formation. We investigated the role of SHP-2 in endothelial cell survival and angiogenesis in vitro as well as in vivo. SHP-2 function in cultured human umbilical vein and human dermal microvascular endothelial cells was inhibited by either silencing the protein expression with antisense-oligodesoxynucleotides or treatment with a pharmacological inhibitor (PtpI IV). SHP-2 inhibition impaired capillary-like structure formation (p < 0.01; n = 8) in vitro as well as new vessel growth ex vivo (p < 0.05; n = 10) and in vivo in the chicken chorioallantoic membrane (p < 0.01, n = 4). Additionally, SHP-2 knock-down abrogated fibroblast growth factor 2 (FGF-2)-dependent endothelial proliferation measured by MTT reduction ( p ! 0.01; n = 12). The inhibitory effect of SHP-2 knock-down on vessel growth was mediated by increased endothelial apoptosis ( annexin V staining, p ! 0.05, n = 9), which was associated with reduced FGF-2-induced phosphorylation of phosphatidylinositol 3-kinase (PI3-K), Akt and extracellular regulated kinase 1/2 (ERK1/2) and involved diminished ERK1/2 phosphorylation after PI3-K inhibition (n=3). These results suggest that SHP-2 regulates endothelial cell survival through PI3-K-Akt and mitogen-activated protein kinase pathways thereby strongly affecting new vessel formation. Thus, SHP-2 exhibits a pivotal role in angiogenesis and may represent an interesting target for therapeutic approaches controlling vessel growth. Copyright (C) 2007 S. Karger AG, Basel

A stochastic mathematical model of 4D tumour spheroids with real-time fluorescent cell cycle labelling

In vitro tumour spheroid experiments have been used to study avascular tumour growth and drug design for the last 50 years. Unlike simpler two-dimensional cell cultures, tumour spheroids exhibit heterogeneity within the growing population of cells that is thought to be related to spatial and temporal differences in nutrient availability. The recent development of real-time fluorescent cell cycle imaging allows us to identify the position and cell cycle status of individual cells within the growing population, giving rise to the notion of a four-dimensional (4D) tumour spheroid. In this work we develop the first stochastic individual-based model (IBM) of a 4D tumour spheroid and show that IBM simulation data qualitatively and quantitatively compare very well with experimental data from a suite of 4D tumour spheroid experiments performed with a primary human melanoma cell line. The IBM provides quantitative information about nutrient availability within the spheroid, which is important because it is very difficult to measure these data in standard tumour spheroid experiments. Software required to implement the IBM is available on GitHub, https://github.com/ProfMJSimpson/4DFUCCI

Application of network traffic flow model to road maintenance

The study shows how the evolution of two-way traffic flows on a local highway network can be predicted over time using a network-level traffic flow model (NTFM) to model both urban and motorway road networks. After a brief review of the main principles of the NTFM and its associated sub-models, the paper describes how a maintenance worksite can be modelled using a roadwork-node sub-model and a network solution routine in the NTFM. In order to model the two-way traffic flow in the road network, an iterative simulation method is used to generate the evolution of dependent traffic flows and queues. The NTFM has been applied to model the traffic characteristics and the effects of maintenance activities on the local Loughborough–Nottingham highway network. The study has demonstrated that the methodology is useful in selecting various worksite arrangements in order to reduce the effects of maintenance on road users

A quantitative PCR (TaqMan) assay for pathogenic Leptospira spp

BACKGROUND: Leptospirosis is an emerging infectious disease. The differential diagnosis of leptospirosis is difficult due to the varied and often "flu like" symptoms which may result in a missed or delayed diagnosis. There are over 230 known serovars in the genus Leptospira. Confirmatory serological diagnosis of leptospirosis is usually made using the microscopic agglutination test (MAT) which relies on the use of live cultures as the source of antigen, often performed using a panel of antigens representative of local serovars. Other techniques, such as the enzyme linked immunosorbent assay (ELISA) and slide agglutination test (SAT), can detect different classes of antibody but may be subject to false positive reactions and require confirmation of these results by the MAT. METHODS: The polymerase chain reaction (PCR) has been used to detect a large number of microorganisms, including those of clinical significance. The sensitivity of PCR often precludes the need for isolation and culture, thus making it ideal for the rapid detection of organisms involved in acute infections. We employed real-time (quantitative) PCR using TaqMan chemistry to detect leptospires in clinical and environmental samples. RESULTS AND CONCLUSIONS: The PCR assay can be applied to either blood or urine samples and does not rely on the isolation and culture of the organism. Capability exists for automation and high throughput testing in a clinical laboratory. It is specific for Leptospira and may discriminate pathogenic and non-pathogenic species. The limit of detection is as low as two cells

Differences in genome-wide gene expression response in peripheral blood mononuclear cells between young and old men upon caloric restriction

Background: Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different nonhuman organisms. Only a limited number of CR studies have been performed on humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a completely controlled 30 % CR diet on immune cells, as immune response is affected during aging. Ten healthy young men, aged 20–28, and nine healthy old men, aged 64–85, were subjected to a 2-week weight maintenance diet, followed by 3 weeks of 30 % CR. Before and after 30 % CR, the whole genome gene expression in peripheral blood mononuclear cells (PBMCs) was assessed. Results: Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in the immune response in young but not in old men. At baseline, immune response-related genes were higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling the immune response. Conclusions: Based on the gene expression data, we theorise that a short period of CR is not effective in old men regarding immune-related pathways while it is effective in young men

Inhibition of TGF-β Signaling and Decreased Apoptosis in IUGR-Associated Lung Disease in Rats

Intrauterine growth restriction is associated with impaired lung function in adulthood. It is unknown whether such impairment of lung function is linked to the transforming growth factor (TGF)-β system in the lung. Therefore, we investigated the effects of IUGR on lung function, expression of extracellular matrix (ECM) components and TGF-β signaling in rats. IUGR was induced in rats by isocaloric protein restriction during gestation. Lung function was assessed with direct plethysmography at postnatal day (P) 70. Pulmonary activity of the TGF-β system was determined at P1 and P70. TGF-β signaling was blocked in vitro using adenovirus-delivered Smad7. At P70, respiratory airway compliance was significantly impaired after IUGR. These changes were accompanied by decreased expression of TGF-β1 at P1 and P70 and a consistently dampened phosphorylation of Smad2 and Smad3. Furthermore, the mRNA expression levels of inhibitors of TGF-β signaling (Smad7 and Smurf2) were reduced, and the expression of TGF-β-regulated ECM components (e.g. collagen I) was decreased in the lungs of IUGR animals at P1; whereas elastin and tenascin N expression was significantly upregulated. In vitro inhibition of TGF-β signaling in NIH/3T3, MLE 12 and endothelial cells by adenovirus-delivered Smad7 demonstrated a direct effect on the expression of ECM components. Taken together, these data demonstrate a significant impact of IUGR on lung development and function and suggest that attenuated TGF-β signaling may contribute to the pathological processes of IUGR-associated lung disease

Arc magmas sourced from melange diapirs in subduction zones

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 5 (2012): 862-867, doi:10.1038/ngeo1634.At subduction zones, crustal material is recycled back into the mantle. A certain proportion, however, is returned to the overriding plate via magmatism. The magmas show a characteristic range of compositions that have been explained by three-component mixing in their source regions: hydrous fluids derived from subducted altered oceanic crust and components derived from the thin sedimentary veneer are added to the depleted peridotite in the mantle beneath the volcanoes. However, currently no uniformly accepted model exists for the physical mechanism that mixes the three components and transports them from the slab to the magma source. Here we present an integrated physico-chemical model of subduction zones that emerges from a review of the combined findings of petrology, modelling, geophysics, and geochemistry: Intensely mixed metamorphic rock formations, so-called mélanges, form along the slab-mantle interface and comprise the characteristic trace-element patterns of subduction-zone magmatic rocks. We consider mélange formation the physical mixing process that is responsible for the geochemical three-component pattern of the magmas. Blobs of low-density mélange material, so-called diapirs, rise buoyantly from the surface of the subducting slab and provide a means of transport for well-mixed materials into the mantle beneath the volcanoes, where they produce melt. Our model provides a consistent framework for the interpretation of geophysical, petrological and geochemical data of subduction zones.H.M. was funded by the J. LamarWorzel Assistant Scientist Fund and the Penzance Endowed Fund in Support of Assistant Scientists. Funding from NSF grant #1119403 (G. Harlow) is acknowledged.2013-05-1