Epithelial damage and loss of intestinal barrier function are hallmark pathologies of the mucosal inflammation associated with conditions such as inflammatory bowel disease. In order to resolve ...inflammation and restore intestinal integrity the mucosa must rapidly and effectively repair the epithelial barrier. Epithelial wound healing is a highly complex and co-ordinated process and the factors involved in initiating intestinal epithelial healing are poorly defined. In order for restitution to be successful there must be a balance between epithelial cell migration, proliferation, and differentiation within and adjacent to the inflamed area. Endogenous, compensatory epithelial signaling pathways are activated by the changes in oxygen tensions that accompany inflammation. These signaling pathways induce the activation of key transcription factors, governing anti-apoptotic, and proliferative processes resulting in epithelial cell survival, proliferation, and differentiation at the site of mucosal inflammation. In this review, we will discuss the primary processes involved in epithelial restitution with a focus on the role of hypoxia-inducible factor and epithelial integrins as mediators of epithelial repair following inflammatory injury at the mucosal surface.
The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus ...during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during
Chlamydia
infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection.
Synopsis
IFNε promotes the accumulation, activation and IFNγ production of NK cells in the uterus through both IL-15-dependent and -independent mechanisms. IFNε-mediated NK cell responses protect against Chlamydia FRT infections.
IFNε is produced exclusively by reproductive tract epithelial cells and acts in the uterus to increase IL-15 production by myeloid cells.
IFNε and IL-15 production in the uterus increases NK cell haematopoiesis in the bone marrow, increasing NK cell numbers systemically, and NK cell accumulation in the uterus.
IFNε acts directly on pre-pro NK cell progenitors in the uterus, promoting their accumulation. IL-15 has no effect on this population.
Local production of IFNε in the uterus is required for optimal NK cell activation during infection and IFNε directly increases NK cell CD69 expression ex vivo.
IL-15 production downstream of IFNε is responsible for promoting NK cell IFNγ production and cytolytic activity. IFNε and IL-15 co-stimulate and are required in concert for full NK cell function.
IFNε promotes the accumulation, activation and IFNγ production of NK cells in the uterus through both IL-15-dependent and -independent mechanisms. IFNε-mediated NK cell responses protect against Chlamydia FRT infections.
Global and local imperfections are required to capture accurate buckling loads and overall structural behaviour of axially loaded structural steel hollow sections in finite element (FE) models. In ...this paper, three methods of geometrical imperfections are considered for square and rectangular structural steel hollow sections: (i) creating the profile of the brace using a half sine wave, (ii) applying an equivalent notional lateral load at mid-length, and (iii) combining sinusoidal local imperfections with an equivalent notional lateral load for global imperfections. When modelling the initial shape of brace members with global imperfection at mid-length of the magnitude used to establish the European buckling curves (L/1000, where L is the length of the brace member), it was found that the equivalent notional lateral load methodology could best predict the buckling capacity of brace members when compared to physical test data and European buckling curves. However, both methodologies neglect the effect of local imperfection on the initial buckling loads. When it was included by generating a continuous sinusoidal wave along the member length, it did not affect the initial buckling loads, but gave a more overall representative behaviour of the brace members.
The FE model is then validated using sixteen cyclic tests for brace members. The FE results are found to match the physical tests values relatively well. In other words, when comparing the ratio of yield force, buckling resistance, and total energy dissipated estimated from the FE model to the measured values in physical tests, the mean values are found to be 1.04, 0.99 and 1.24, respectively, with a coefficient of variation of 0.07, 0.07 and 0.17, respectively.
•3 methods of geometrical imperfections are examined for structural steel sections.•The application is brace members under cyclic axial loading.•A parametric study using FEM was conducted to find most appropriate method.•Conclusion is to apply an equivalent notional lateral load & local sinusoidal waves.•The methodology was validated using sixteen cyclic tests for brace members.
As part of an on-going research project on the hybrid precast lattice girder floor system, a series of six specimens were physically tested in the laboratory to investigate the behaviour of the floor ...at construction stage. The purpose of the experimental tests was to improve the understanding of the floor system at construction stage and examine the key parameters which influence its behaviour at both serviceability and ultimate limit states. The results suggest that there is scope for further optimisation of the lattice girder floor system and that the current design methods may be overly conservative.
The lack of comprehensive test data on this floor system limits the development of accurate models which can predict the behaviour of the floor during construction. In this paper, the developments of strain in the various components of the floor system (lattice girder, concrete plank and reinforcement) are measured for a range of lattice girder planks. The use of the transformed area method and Eurocode 3 to predict the behaviour of the plank are investigated in this paper. The analytical model developed is shown to be relatively accurate for predicting the initial stiffness and deflection of planks with tall girders but is not appropriate for planks with low height girders. Areas requiring further research are recommended in this paper to allow formulation of a generic model which would predict the behaviour of the floor system accurately at construction stage.
Structural optimisation of a wind turbine blade is presented in this work. The optimisation was performed using a multi-objective genetic algorithm and finite element modelling to determine the ...optimal structural design for a glass fibre-reinforced polypropylene composite blade. A candidate blade design from the Pareto efficient set was manufactured and tested for a range of structural characteristics, including: mass, centre of gravity, deflections, strains and natural frequencies. Static testing was carried out using a Whiffle tree test rig and a laser scanner was used to determine the deflection of the blade to a high degree of accuracy. The finite element model results for the custom-made design are compared to the measured blade response. The FE model predictions for strains, mass and natural frequencies are in relatively good agreement with the test results; however, notable deviations in the deflections predictions are attributed to modifications to the blade for manufacture and the shell-based modelling approach. The differences are discussed in detail and recommendations for future design work are outlined. The test results of the bespoke blade are also compared to two additional designs to determine the level of improvement afforded by the genetic algorithm approach. The bespoke glass fibre blade demonstrated an improvement in tip deflection of 16% relative to the original blade design, with a slight decrease in mass.
This paper describes an experimental study on the response of hollow and filled steel members to monotonic and cyclic axial loading. Monotonic tests were first performed on short specimens to ...establish their compressive and tensile axial resistances and to investigate the effect of infill on local buckling and ductility. These were followed by cyclic tests on longer bracing members with three different cross-section sizes. The presence of concrete infill was observed to influence the mode of failure displayed by the specimens, as well as their compression and tension load responses. The ductility capacities of the individual specimens are compared, and the effects of slenderness, steel strength and infill are quantified. The experimental findings are compared with the recommendations of a number of international codes of practice and previous research studies on the seismic response of steel braces. It is found that the infill contributes to the compression resistance of the brace, even after multiple inelastic load reversals, and that it can improve ductility capacity by preventing or limiting local buckling.
This work presents an experimental investigation into the permeability of carbon fibre (CF) polyetheretherketone (PEEK) for cryogenic storage tanks for space applications. The effects of cryogenic ...cycling, manufacturing method, PEEK matrix type, fibre type, cryogenic temperatures, pressure, and thickness on the permeability of CF-PEEK laminates are investigated. Laminates are manufactured using autoclave, press and in-situ laser assisted automated tape placement (ATP) consolidation. Optical microscopy is used to characterise the microstructure of test samples. The results show that, for undamaged autoclaved CF-PEEK samples, the permeability remains essentially constant for the ranges of pressures and thicknesses tested. Samples manufactured using the ATP process and samples which were damaged by cryogenic cycling, had a higher leak rate than autoclaved and pressed samples. For cryogenically cycled samples, the leak rate was shown to be dependent on the damage state of the microstructure.
When carrying out any numerical modelling it is useful to have an analytical approximation available to provide a check on the accuracy of the numerical results and to give insight into the ...underlying physics of the system. The numerical modelling of wave energy converters is an efficient and inexpensive method of undertaking initial optimisation and experimentation. Therefore, the main objective of this paper is to determine an analytical approximation for the wave excitation forces on a floating truncated vertical cylinder in water of infinite depth. The approximation is developed by solving appropriate boundary value problems using the method of separation of variables. A graphical representation of the analytical approximation for the truncated vertical cylinder and the cylinder of infinite depth are presented and are compared to the results from a computational fluid dynamics analysis, using a commercial boundary element package. The presented analytical approximation and the computational fluid dynamics analysis results were found to be in good agreement. Furthermore, the presented analytical approximation was found to be in good agreement with independent experimental data.
While factors affecting the course of knee osteoarthritis are mostly unknown, lesions on bone scan and mechanical malalignment increase risk for radiographic deterioration. Bone marrow edema lesions ...on magnetic resonance imaging correspond to bone scan lesions.
To determine whether edema lesions in the subarticular bone in patients with knee osteoarthritis identify knees at high risk for radiographic progression and whether these lesions are associated with limb malalignment.
Natural history study.
A Veterans Administration hospital in Boston, Massachusetts.
Persons 45 years of age and older with symptomatic knee osteoarthritis.
Baseline assessments included magnetic resonance imaging of the knee and fluoroscopically positioned radiography. During follow-up at 15 and 30 months, patients underwent repeated radiography; at 15 months, long-limb films were obtained to assess mechanical alignment. Progression was defined as an increase over follow-up in medial or lateral joint space narrowing, based on a semi-quantitative grading. Generalized estimating equations were used to evaluate the relation of medial bone marrow edema lesions to medial progression and lateral lesions to lateral progression, before and after adjustment for limb alignment.
Of 256 patients, 223 (87.1%) participated in at least one follow-up examination. Medial bone marrow lesions were seen mostly in patients with varus limbs, and lateral lesions were seen mostly in those with valgus limbs. Twenty-seven of 75 knees with medial lesions (36.0%) showed medial progression versus 12 of 148 knees without lesions (8.1%) (odds ratio for progression, 6.5 95% CI, 3.0 to 14.0). Approximately 69% of knees that progressed medially had medial lesions, and lateral lesions conferred a marked risk for lateral progression. These increased risks were attenuated by 37% to 53% after adjustment for limb alignment.
Bone marrow edema is a potent risk factor for structural deterioration in knee osteoarthritis, and its relation to progression is explained in part by its association with limb alignment.
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