Abstract
Typhoid fever, caused by infection with Salmonella bacteria affects approximately 21 million people annually, killing nearly 200,000 and yet the immunological response to this infection is ...poorly understood. Recent thymic emigrants (RTEs) are the youngest subset of peripheral T cells, which are known to differ in how they functionally contribute to the naïve T cell pool. This distinctive cell population is known to contribute to the maintenance of T cell receptor diversity in the peripheral T cell pool, but their involvement in combating chronic bacterial infections, such as typhoid fever, has not been explored. In the present study, we hypothesized that RTEs are essential contributors to the CD4 T cell response during persistent Salmonella Typhimurium (ST) infection, which predominantly relies on helper T cell immunity to control bacteria. Here, we show that thymectomy of adult mice prior to oral infection with ST leads to increased mortality in addition to significantly increased bacterial burdens in the spleen, mesenteric lymph nodes and liver 30 days post-infection compared to sham surgical controls, suggesting Salmonella-specific RTEs may contribute to bacterial clearance. Surprisingly, thymectomized animals also demonstrated expanded numbers of peripheral Salmonella-specific T cells, compared to control animals, implying that these existing cells are somehow incapable of controlling infection in the absence of RTEs. The results of this study provide insight into how new pathogen-specific T cells leaving the thymus participate in combatting a persistent bacterial infection.
Purpose - The purpose of this paper is to focus on a number of initiatives in civil engineering undergraduate programmes at the National University of Ireland, Galway (NUIG) that allow students to ...complete engineering projects in the community, enabling them to learn by doing.Design methodology approach - A formal commitment to civic engagement was undertaken by the NUIG in 2001 with the establishment of the Community Knowledge Initiative (CKI) to work on mainstreaming civic engagement (service learning) within the curriculum across the institution. Today, the majority of undergraduate and postgraduate degree programmes in the College of Engineering and Informatics at NUIG have embedded service learning into their curriculum. These initiatives allow students to work with and in local communities, international communities and multi-disciplinary groups as part of their academic courses. The paper investigates and shows that community-based projects can enhance student learning and engagement in a number of ways. At NUIG, these projects are framed by a research orientation, commitments to civic engagement and building university-community partnerships, city-university partnerships and partnerships with other official agencies, so that community users can provide real learning problems and contexts for students and researchers and benefit from the results.Findings - It was found that the students got a sense of pride and satisfaction out of the knowledge that their work may be helping communities and that learning is not just to get marks to pass the exam! The projects can increase the students' sense of ownership of their own learning. Learners are more motivated when they can see the usefulness of what they are learning and when they can use that information to do something that has an impact on others.Research limitations implications - The work represents work done in one institution affecting a region in a country. This can be extended to include more institutions and other regions. This paper presents evidence from the aforementioned projects that by creating service-based learning the students' energy in learning can have a positive impact on the community.Practical implications - The energy and enthusiasm of learners can be better utilised (and increased) by setting assignments as real community-based projects.Originality value - This lies in the design of projects and assessment involving education providers and public for the benefit of learners and the society at large.
A direct displacement based design (DDBD) methodology for concentrically braced frames (CBFs) is validated using a combination of experimental and numerical data taking into account the behaviour of ...brace-beam-column connections. Twelve full-scale shake table tests with four different brace cross-section sizes, two different gusset plate design methodologies and two different brace connection configurations are used to evaluate the design procedure at three different performance levels (continued operation, life safety and collapse/near collapse) through successive scaling of test excitations.
It is found that the DDBD procedure can predict the behaviour of the shake table CBFs for the three levels of excitation. Accurate results have been found for life safety design where the mean ratio and coefficient of variation of base shear (Fb) calculated using the DDBD method to the values found from shake table tests are 0.96 and 0.17, respectively. Furthermore, the mean ratio and coefficient of variation of brace area (Ab) calculated from the DDBD method to the values used in shake table tests are 1 and 0.08, respectively.
The design procedure was also verified using nonlinear time history analysis (NLTHA) using a selection of earthquake records with displacement spectra compatible with those of the exact accelerograms recorded during the shake table tests. At the life safety performance level, the mean peak displacement demand and base shear values obtained from NLTHA were observed to be 82% and 91%, respectively, of the design values determined by the DDBD methodology.
•A direct displacement based design (DDBD) methodology for steel CBFs is validated.•The DDBD procedure can predict the behaviour observed in physical shake table tests.•The design procedure was also verified using nonlinear time history analysis (NLTHA).•Accurate results have been found for life safety design.
Abstract
Typhoid fever, caused by infection with Salmonella bacteria affects approximately 21 million people annually, killing nearly 200,000. Recent thymic emigrants (RTEs) are the youngest subset ...of peripheral T cells, which are known to differ in how they functionally contribute to the naïve T cell pool. This distinctive cell population is known to contribute to the maintenance of T cell receptor diversity in the peripheral T cell pool, but their involvement in combating chronic bacterial infections, such as typhoid fever, has not been explored. In the present study, we hypothesized that RTEs are essential contributors to the CD4 T cell response during persistent Salmonella Typhimurium (ST) infection, which predominantly relies on helper T cell immunity to control bacteria. Here, we show that thymectomy of adult mice prior to oral infection with ST led to significantly increased bacterial burdens in the spleen, mesenteric lymph nodes and liver 30 days post-infection compared to sham surgical controls, suggesting Salmonella-specific RTEs may contribute to bacterial clearance. Surprisingly, existing peripheral Salmonella-specific T cells also increased significantly in number, implying that these cells are somehow incapable of controlling infection in the absence of RTEs. The results of this study provide insight into how new pathogen-specific T cells leaving the thymus participate in combatting a persistent bacterial infection.
To test whether a lateral-wedged insole, inclined at 5 degrees or 10 degrees, significantly reduces knee varus torque during walking in patients with knee osteoarthritis compared with both using no ...insole and with wearing nonwedged control insoles of the same material and average thickness.
Patients with medial knee osteoarthritis were studied while they walked wearing their comfortable shoes (1) without an insole; (2) with a 5 degrees lateral wedge compared with a nonwedged, 3.175-mm (1/8-in) even-thickness control insole; and (3) with a 10 degrees lateral wedge compared with a nonwedged 6.35-mm ((1/4)-in) even-thickness control insole.
A gait laboratory with 3-dimensional motion analysis and force platform equipment.
Fifteen patients with clinical and radiographic osteoarthritis of the medial compartment of 1 knee.
Not applicable.
Peak external knee varus torques during the stance period of gait. Data regarding lower-extremity joint torques and motions were collected, and knee joint torques using the different insoles and wedges were compared by analysis of variance.
Although responses varied among individuals, as a group, both the 5 degrees and 10 degrees lateral-wedge insoles significantly reduced the knee varus torque during walking compared with walking with no insole and walking with nonwedged 3.175-mm and 6.35-mm control insoles. Compared with no insole, the 5 degrees wedge reduced the peak knee varus torque values by about 6% and the 10 degrees wedge reduced the peaks by about 8%. Although there were no significant differences in speed of walking between the conditions, the 10 degrees wedge and 6.35-mm control insoles were associated with varying degrees of discomfort.
Both wedge insoles are effective in reducing the varus torque during walking beyond what theoretically could be explained by a reduced walking speed or cushioning effect from the insole. These data imply that wedged insoles are biomechanically effective and should reduce loading of the medial compartment in persons with medial knee osteoarthritis. Although the effect of the 5 degrees wedge was smaller, it may be more comfortable than the 10 degrees wedge to wear inside one's own shoes.
A design methodology that addresses the modelling of ductile steel behaviour in a unified format is presented. In this methodology, three empirical laws defined as Hook's Law, Hollomon Law, Modified ...Weighted Average Law and a crack driven law based on the extended finite element method (XFEM) are linked empirically and systematically to format an advanced design approach. A set of test data representing forty-five coupon tests of 40 × 40 × 2.5, 20 × 20 × 2.0, and 50 × 25 × 2.5 (mm) square and rectangular steel hollow sections is used to demonstrate its applicability and effectiveness in driving the material model. The material model developed is employed in a robust numerical model of the steel hollow sections. Another set of data representing twenty-three monotonic static tests of steel hollow sections is employed to validate the XFEM model's performance. The XFEM results are found to match the physical tests values relatively well. In other words, when comparing the ratio of yield force, ultimate displacement, and energy dissipation capacity estimated from the finite element (FE) model to the measured values in the physical test, the mean values are found to be 1.03, 1.08, and 1.05 with a coefficient of variation of 0.05, 0.19, and 0.19, respectively. Hence, the design methodology presented and the XFEM model developed can be used with confidence as they have been calibrated and validated using the test data.
Osteoarthritis (OA) is a multifactorial condition. The progression of knee OA is determined in part by mechanical effects on local structures. One of the mechanical influences on cartilage loss is ...limb alignment. We explored the structural factors associated with malalignment in subjects with symptomatic OA.
We conducted a cross-sectional assessment using The Boston Osteoarthritis of the Knee Study, a natural history study of symptomatic knee OA. Baseline assessments included knee magnetic resonance imaging (MRI) and information on weight and height. Long-limb radiographs to assess mechanical alignment were obtained at 15 months. Subarticular bone attrition, meniscal degeneration, anterior and posterior cruciate ligament integrity, medial and lateral collateral ligament integrity, marginal osteophytes, and cartilage morphology were assessed on MRI using a semiquantitative, multi-feature scoring method (Whole-Organ MRI Score) for whole-organ evaluation of the knee that is applicable to conventional MRI techniques. We also quantified the following meniscal position measures on coronal MRI images in both medial and lateral compartments: subluxation, meniscal height, and meniscal covering of the tibial plateau. Using the long-limb radiographs, mechanical alignment was measured in degrees on a continuous scale. The purpose of this cross-sectional analysis was to determine the individual and relative contribution of various structural factors to alignment of the lower extremity. We assessed the cross-sectional association between various structural factors and alignment of the lower extremity using a linear regression model.
The 162 subjects with all measures acquired had a mean age of 67.0 years (SD 9.2), body mass index 31.4 (SD 5.6); 30% were female and 77% of knees had a Kellgren-Lawrence grade > or = 2. The main univariate determinants of varus alignment in decreasing order of influence were medial bone attrition, medial meniscal degeneration, medial meniscal subluxation, and medial tibiofemoral cartilage loss. Multivariable analysis revealed that medial bone attrition and medial tibiofemoral cartilage loss explained more of the variance in varus malalignment than other variables. The main univariate determinants of valgus malalignment in decreasing order of influence were lateral tibiofemoral cartilage loss, lateral osteophyte score, and lateral meniscal degeneration.
Cartilage loss has been thought to be the major determinant of alignment. We found that other factors including meniscal degeneration and position, bone attrition, osteophytes, and ligament damage contribute to the variance of malalignment. Further longitudinal analysis is required to determine cause and effect relationships. This should assist researchers in determining strategies to ameliorate the potent effects of this mechanical disturbance.
This paper describes an experimental investigation into the seismic response of concentrically braced steel frames (CBFs). Twelve shake table tests were performed on full-scale single storey frames, ...each containing a pair of identical brace members. The experimental programme examined the behaviour of brace members with four different square and rectangular hollow cross-sections and a range of gusset plate connection details. The aim of the experimental study was to determine the influence of brace and gusset plate properties on CBF response from serviceability to ultimate limit states, including collapse. Consequently, all test frames were subjected to three levels of seismic excitation: (i) low-level excitation to examine elastic frame response, (ii) medium-level excitation to examine brace buckling and yielding effects, and (iii) high-level excitation to induce brace fracture. A detailed set of data on the seismic response of CBFs with realistic brace members and connections were obtained from the tests. The experiments were conducted under representative dynamic response conditions as opposed to the conventional idealised quasi-static loading procedures employed in previous experimental investigations of CBF behaviour. The results faithfully capture the behaviour of brace-gusset plate test specimens with different non-dimensional brace slenderness, brace cross-section slenderness, connection types and gusset plate detailing. The response variables measured in each test included the shaking table and frame accelerations and displacements, brace elongation and axial force, and brace member and gusset plate strains. The experimental observations include elastic frame vibration properties, acceleration and drift demands, ultimate failure modes and ductility capacity. The brace-gusset plate test specimens remained elastic at low-level excitations, brace buckling and yielding occurred in all medium-level excitation tests, while specimens exhibited brace fracture under high-level excitation. Fracture did not occur in the gusset plate connections irrespective of whether these were designed using a conventional design method with a Standard Linear Clearance (SLC), or a balanced design with an Elliptical Clearance (EC). However, the balanced design approach showed more uniform distribution of plastic strains and led to higher brace ductility capacities when compared to the conventional design method. Based on the test results, available methods for predicting the ductility of bracing members are compared and assessed, and a number of considerations for design are highlighted and discussed.
Conventional seismic design of concentrically braced frame (CBF) structures suggests that the gusset plate connecting a steel brace to beams and/or columns should be designed as non-dissipative in ...earthquakes, while the steel brace members should be designed as dissipative elements. These design intentions lead to thicker and larger gusset plates in design on one hand and a potentially under-rated contribution of gusset plates in design, on the other hand. In contrast, research has shown that compact and thinner gusset plates designed in accordance with the elliptical clearance method rather than the conventional standard linear clearance method can enhance system ductility and energy dissipation capacity in concentrically braced steel frames. In order to assess the two design methods, six cyclic push-over tests on full scale models of concentric braced steel frame structures were conducted. Furthermore, a 3D finite element (FE) shell model, incorporating state-of-the-art tools and techniques in numerical simulation, was developed that successfully replicates the response of gusset plate and bracing members under fully reversed cyclic axial loading. Direct measurements from strain gauges applied to the physical models were used primarily to validate FE models, while comparisons of hysteresis load-displacement loops from physical and numerical models were used to highlight the overall performance of the FE models. The study shows the two design methods attain structural response as per the design intentions; however, the elliptical clearance method has a superiority over the standard linear method as a fact of improving detailing of the gusset plates, enhancing resisting capacity and improving deformability of a CBF structure. Considerations were proposed for improvement of guidelines for detailing gusset plates and bracing members in CBF structures.
