CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

The assumption that mesenchymal stromal cell (MSC)-based therapies are capable of augmenting physiological regeneration processes has fostered intensive basic and clinical research activities. However, to achieve sustained therapeutic success in vivo, not only the biological, but also the mechanical microenvironment of MSCs during these regeneration processes needs to be taken into account. This is especially important for e.g., bone fracture repair, since MSCs present at the fracture site undergo significant biomechanical stimulation. This study has therefore investigated cellular characteristics and the functional behaviour of MSCs in response to mechanical loading. Our results demonstrated a reduced expression of MSC surface markers CD73 (ecto-5’-nucleotidase) and CD29 (integrin β1) after loading. On the functional level, loading led to a reduced migration of MSCs. Both effects persisted for a week after the removal of the loading stimulus. Specifi c inhibition of CD73/CD29 demonstrated their substrate dependent involvement in MSC migration after loading. These results were supported by scanning electron microscopy images and phalloidin staining of actin fi laments displaying less cell spreading, lamellipodia formation and actin accumulations. Moreover, focal adhesion kinase and Src-family kinases were identified as candidate downstream targets of CD73/CD29 that might contribute to the mechanically induced decrease in MSC migration. These results suggest that MSC migration is controlled by CD73 CD29, which in turn are regulated by mechanical stimulation of cells. We therefore speculate that MSCs migrate into the fracture site, become mechanically entrapped, and thereby accumulate to fulfil their regenerative functions.

Seismic capacity of building constructed in slip formed load bearing wall panels

Constructing buildings using slip formed load bearing wall panels is becoming increasingly popular in Sri Lanka due to several advantages; low cost, environmental friendliness and rapid construction technique. These wall panels are already successfully implemented in many low rise buildings. However, the seismic capacities of these buildings have not been properly studied. Few seismic activities reported in Sri Lanka have not caused severe structural damage, but predictions can not be made as to whether this will continue to be the case in the future. This highlights the need to study the seismic capacity of buildings constructed in slip formed load bearing wall panels. This paper presents a study of the seismic capacity of the existing medium rise building.

A collagen network phase improves cell seeding of open-pore structure scaffolds under perfusion

Scaffolds with open-pore morphologies offer several advantages in cell-based tissue engineering, but their use is limited by a low cell seeding efficiency. We hypothesized that inclusion of a collagen network as filling material within the open-pore architecture of polycaprolactone-tricalcium phosphate (PCL-TCP) scaffolds increases human bone marrow stromal cells (hBMSC) seeding efficiency under perfusion and in vivo osteogenic capacity of the resulting constructs. PCL-TCP scaffolds, rapid prototyped with a honeycomb-like architecture, were filled with a collagen gel and subsequently lyophilized, with or without final crosslinking. Collagen-free scaffolds were used as controls. The seeding efficiency was assessed after overnight perfusion of expanded hBMSC directly through the scaffold pores using a bioreactor system. By seeding and culturing freshly harvested hBMSC under perfusion for 3 weeks, the osteogenic capacity of generated constructs was tested by ectopic implantation in nude mice. The presence of the collagen network, independently of the crosslinking process, significantly increased the cell seeding efficiency (2.5-fold), and reduced the loss of clonogenic cells in the supernatant. Although no implant generated frank bone tissue, possibly due to the mineral distribution within the scaffold polymer phase, the presence of a non crosslinked collagen phase led to in vivo formation of scattered structures of dense osteoids. Our findings verify that the inclusion of a collagen network within open morphology porous scaffolds improves cell retention under perfusion seeding. In the context of cell-based therapies, collagen-filled porous scaffolds are expected to yield superior cell utilization, and could be combined with perfusion-based bioreactor devices to streamline graft manufacture.

Busway platform bus capacity analysis

Bus Rapid Transit (BRT), because of its operational flexibility and simplicity, is rapidly gaining popularity with urban designers and transit planners. Earlier BRTs were bus shared lane or bus only lane, which share the roadway with general and other forms of traffic. In recent time, more sophisticated designs of BRT have emerged, such as busway, which has separate carriageway for buses and provides very high physical separation of buses from general traffic. Line capacities of a busway are predominately dependent on bus capacity of its stations. Despite new developments in BRT designs, the methodology of capacity analysis is still based on traditional principles of kerbside bus stop on bus only lane operations. Consequently, the tradition methodology lacks accounting for various dimensions of busway station operation, such as passenger crowd, passenger walking and bus lost time along the long busway station platform. This research has developed a purpose made bus capacity analysis methodology for busway station analysis. Extensive observations of kerbside bus stops and busway stations in Brisbane, Australia were made and differences in their operation were studied. A large scale data collection was conducted using the video recording technique at the Mater Hill Busway Station on the South East Busway in Brisbane. This research identified new parameters concerning busway station operation, and through intricate analysis identified the elements and processes which influence the bus dwell time at a busway station platform. A new variable, Bus lost time, was defined and its quantitative descriptions were established. Based on these finding and analysis, a busway station platform bus capacity methodology was developed, comprising of new models for busway station lost time, busway station dwell time, busway station loading area bus capacity, and busway station platform bus capacity. The new methodology not only accounts for passenger boarding and alighting, but also covers platform crowd and bus lost time in station platform bus capacity estimation. The applicability of this methodology was shown through demonstrative examples. Additionally, these examples illustrated the significance of the bus lost time variable in determining station capacities.

Relative entropy rate based design for linear hybrid system models

Hybrid system representations have been applied to many challenging modeling situations. In these hybrid system representations, a mixture of continuous and discrete states is used to capture the dominating behavioural features of a nonlinear, possible uncertain, model under approximation. Unfortunately, the problem of how to best design a suitable hybrid system model has not yet been fully addressed. This paper proposes a new joint state measurement relative entropy rate based approach for this design purpose. Design examples and simulation studies are presented which highlight the benefits of our proposed design approaches.

A Multifaceted Strategy for Implementation of the Ottawa Ankle Rules in Two Emergency Departments

Problem Despite widespread acceptance of the Ottawa ankle rules for assessment of acute ankle injuries, their application varies considerably. Design Before and after study. Background and setting Emergency departments of a tertiary teaching hospital and a community hospital in Australia. Key measures for improvement Documentation of the Ottawa ankle rules, proportion of patients referred for radiography, proportion of radiographs showing a fracture. Strategies for change Education, a problem specific radiography request form, reminders, audit and feedback, and using radiographers as “gatekeepers.” Effects of change Documentation of the Ottawa ankle rules improved from 57.5% to 94.7% at the tertiary hospital, and 51.6% to 80.8% at the community hospital (P<0.001 for both). The proportion of patients undergoing radiography fell from 95.8% to 87.2% at the tertiary hospital, and from 91.4% to 78.9% at the community hospital (P<0.001 for both). The proportion of radiographs showing a fracture increased from 20.4% to 27.1% at the tertiary hospital (P=0.069), and 15.2% to 27.2% (P=0.002) at the community hospital. The missed fracture rate increased from 0% to 2.9% at the tertiary hospital and from 0% to 1.6% at the community hospital compared with baseline (P=0.783 and P=0.747). Lessons learnt Assessment of case note documentation has limitations. Clinician groups seem to differ in their capacity and willingness to change their practice. A multifaceted change strategy including a problem specific radiography request form can improve the selection of patients for radiography.

Manufacturing practices and performances: A Malaysian study

The purpose of this study is to identify the most common manufacturing practices adopted by the Malaysian manufacturers, company performance factors and relationship between practices and performances. To fulfil the study objectives, 400 manufacturers were surveyed by a standard 400 questionnaire. Three research methodologies such as descriptive analysis, ANOVA and regression analysis have been employed in this study. The analysis revealed that Malaysian manufacturers focus on optimizing three critical performance factors: product development, less customer return rate and on time delivery (OTD). The most important competitive factor was found to be company reputation and design and manufacturing capacity is the least important factor. The findings also proved that manufacturing practices significantly influence company performances