Osteogenic induction of human bone marrow-derived mesenchymal progenitor cells in novel synthetic polymer-hydrogel matrices

The aim of this project was to investigate the in vitro osteogenic potential of human mesenchymal progenitor cells in novel matrix architectures built by means of a three-dimensional bioresorbable synthetic framework in combination with a hydrogel. Human mesenchymal progenitor cells (hMPCs) were isolated from a human bone marrow aspirate by gradient centrifugation. Before in vitro engineering of scaffold-hMPC constructs, the adipogenic and osteogenic differentiation potential was demonstrated by staining of neutral lipids and induction of bone-specific proteins, respectively. After expansion in monolayer cultures, the cells were enzymatically detached and then seeded in combination with a hydrogel into polycaprolactone (PCL) and polycaprolactone-hydroxyapatite (PCL-HA) frameworks. This scaffold design concept is characterized by novel matrix architecture, good mechanical properties, and slow degradation kinetics of the framework and a biomimetic milieu for cell delivery and proliferation. To induce osteogenic differentiation, the specimens were cultured in an osteogenic cell culture medium and were maintained in vitro for 6 weeks. Cellular distribution and viability within three-dimensional hMPC bone grafts were documented by scanning electron microscopy, cell metabolism assays, and confocal laser microscopy. Secretion of the osteogenic marker molecules type I procollagen and osteocalcin was analyzed by semiquantitative immunocytochemistry assays. Alkaline phosphatase activity was visualized by p-nitrophenyl phosphate substrate reaction. During osteogenic stimulation, hMPCs proliferated toward and onto the PCL and PCL-HA scaffold surfaces and metabolic activity increased, reaching a plateau by day 15. The temporal pattern of bone-related marker molecules produced by in vitro tissue-engineered scaffold-cell constructs revealed that hMPCs differentiated better within the biomimetic matrix architecture along the osteogenic lineage.

Designed biodegradable hydrogel structures prepared by stereolithography using poly(ethylene glycol)/poly(D,L-lactide)-based resins

Designed three-dimensional biodegradable poly(ethylene glycol)/poly(D,L-lactide) hydrogel structures were prepared for the first time by stereolithography at high resolutions. A photopolymerisable aqueous resin comprising PDLLA-PEG-PDLLA-based macromer, visible light photo-initiator, dye and inhibitor in DMSO/water was used to build the structures. Porous and non-porous hydrogels with well-defined architectures and good mechanical properties were prepared. Porous hydrogel structures with a gyroid pore network architecture showed narrow pore size distributions, excellent pore interconnectivity and good mechanical properties. The structures showed good cell seeding characteristics, and human mesenchymal stem cells adhered and proliferated well on these materials.

Integrating SOA into an Enterprise Architecture : a comparative analysis of alternative approaches

Enterprise Architectures have emerged as comprehensive corporate artefacts that provide structure to the plethora of conceptual views on an enterprise. The recent popularity of a service-oriented design of organizations has added service and related constructs as a new element that requires consideration within an Enterprise Architecture. This paper analyzes and compares the existing proposals for how to best integrate services into Enterprise Architectures. It uses the popular Zachman Framework as an example and differentiates the existing integration alternatives. This research can be generalized beyond service integration into an investigation onto how to possibly extend Enterprise Architectures with emerging constructs.

Properties of photo-cured poly(D,L-lactide) networks

Poly(D,L-lactide) is a degradable polymer with a long history of use in medical applications. It is strong and stiff and degrades over the course of months into lactic acid, a body-own substance. In the field of tissue engineering it is commonly used to fabricate scaffolds. Stereolithography is a high resolution rapid prototyping technique by which designed 3D objects can be built using photo-initiated radical polymerisations. Poly(D,Llactide) (PDLLA) networks can be obtained by photopolymerisation of oligomers functionalised with unsaturated groups. In this work, PDLLA oligomers of varying architectures (arm lengths, numbers of arms) were synthesised and end-functionalised with methacrylate groups. These macromers were photo-crosslinked in solution to yield PDLLA networks of different architectures. The influence of the network architecture on its physical properties was studied.

Poly(D,L-lactide)/hydroxyapatite composite tissue engineering scaffolds prepared by stereolithography

Hydroxyapatite (HAP) is a major component of bone and has osteoconductive and -inductive properties. It has been successfully applied as a substrate in bone tissue engineering, either with or without a biodegradable polymer such as polycaprolactone or polylactide. Recently, we have developed a stereolithography resin based on poly(D,L-lactide) (PDLLA) and a non-reactive diluent, that allows for the preparation of tissue engineering scaffolds with designed architectures. In this work, designed porous composite structures of PDLLA and HAP are prepared by stereolithography.

Designed poly(ethylene glycol)/poly(D,L-lactide)-based hydrogel structures prepared by stereolithography

Three-dimensional biodegradable poly(ethylene glycol)/poly(D,L-lactide) hydrogel structures were prepared by stereolithography. A photo-polymerisable liquid resin comprising PDLLA-PEG-PDLLA-based macromer, visible light photo-initiator, dye and inhibitor in DMSO/water was used to build the structures. Hydrogels with welldefined architectures and good mechanical properties were prepared. Hydrogel structures with a gyroid pore network architecture showed narrow pore size distributions, excellent pore interconnectivity and good mechanical properties. The structures showed good cell seeding characteristics, and human mesenchymal stem cells adhered and proliferated on these materials.

Smart Grid Test Bed Design and Implementation

Given there is currently a migration trend from traditional electrical supervisory control and data acquisition (SCADA) systems towards a smart grid based approach to critical infrastructure management. This project provides an evaluation of existing and proposed implementations for both traditional electrical SCADA and smart grid based architectures, and proposals a set of reference requirements which test bed implementations should implement. A high-level design for smart grid test beds is proposed and initial implementation performed, based on the proposed design, using open source and freely available software tools. The project examines the move towards smart grid based critical infrastructure management and illustrates the increased security requirements. The implemented test bed provides a basic framework for testing network requirements in a smart grid environment, as well as a platform for further research and development. Particularly to develop, implement and test network security related disturbances such as intrusion detection and network forensics. The project undertaken proposes and develops an architecture of the emulation of some smart grid functionality. The Common Open Research Emulator (CORE) platform was used to emulate the communication network of the smart grid. Specifically CORE was used to virtualise and emulate the TCP/IP networking stack. This is intended to be used for further evaluation and analysis, for example the analysis of application protocol messages, etc. As a proof of concept, software libraries were designed, developed and documented to enable and support the design and development of further smart grid emulated components, such as reclosers, switches, smart meters, etc. As part of the testing and evaluation a Modbus based smart meter emulator was developed to provide basic functionality of a smart meter. Further code was developed to send Modbus request messages to the emulated smart meter and receive Modbus responses from it. Although the functionality of the emulated components were limited, it does provide a starting point for further research and development. The design is extensible to enable the design and implementation of additional SCADA protocols. The project also defines an evaluation criteria for the evaluation of the implemented test bed, and experiments are designed to evaluate the test bed according to the defined criteria. The results of the experiments are collated and presented, and conclusions drawn from the results to facilitate discussion on the test bed implementation. The discussion undertaken also present possible future work.

V2V/V2I augmented maps : state-of-the-art and contribution to real-time crash risk assessment

A number of advanced driver assistance systems (ADAS) are currently being released on the market, providing safety functions to the drivers such as collision avoidance, adaptive cruise control or enhanced night-vision. These systems however are inherently limited by their sensory range: they cannot gather information from outside this range, also called their “perceptive horizon”. Cooperative systems are a developing research avenue that aims at providing extended safety and comfort functionalities by introducing vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) wireless communications to the road actors. This paper presents the problematic of cooperative systems, their advantages and contributions to road safety and exposes some limitations related to market penetration, sensors accuracy and communications scalability. It explains the issues of how to implement extended perception, a central contribution of cooperative systems. The initial steps of an evaluation of data fusion architectures for extended perception are exposed.

Engineering an Ecosystem : Taking Cues from Nature’s Paradigm to Build Tissue in the Lab and the Body

This manuscript took a 'top down' approach to understanding survival of inhabitant cells in the ecosystem bone, working from higher to lower length and time scales through the hierarchical ecosystem of bone. Our working hypothesis is that nature “engineered” the skeleton using a 'bottom up' approach,where mechanical properties of cells emerge from their adaptation to their local me-chanical milieu. Cell aggregation and formation of higher order anisotropic struc- ture results in emergent architectures through cell differentiation and extracellular matrix secretion. These emergent properties, including mechanical properties and architecture, result in mechanical adaptation at length scales and longer time scales which are most relevant for the survival of the vertebrate organism [Knothe Tate and von Recum 2009]. We are currently using insights from this approach to har-ness nature’s regeneration potential and to engineer novel mechanoactive materials [Knothe Tate et al. 2007, Knothe Tate et al. 2009]. In addition to potential applications of these exciting insights, these studies may provide important clues to evolution and development of vertebrate animals. For instance, one might ask why mesenchymal stem cells condense at all? There is a putative advantage to self-assembly and cooperation, but this advantage is somewhat outweighed by the need for infrastructural complexity (e.g., circulatory systems comprised of specific differentiated cell types which in turn form conduits and pumps to overcome limitations of mass transport via diffusion, for example; dif-fusion is untenable for multicellular organisms larger than 250 microns in diameter. A better question might be: Why do cells build skeletal tissue? Once cooperatingcells in tissues begin to deplete local sources of food in their aquatic environment, those that have evolved a means to locomote likely have an evolutionary advantage. Once the environment becomes less aquarian and more terrestrial, self-assembled organisms with the ability to move on land might have conferred evolutionary ad-vantages as well. So did the cytoskeleton evolve several length scales, enabling the emergence of skeletal architecture for vertebrate animals? Did the evolutionary advantage of motility over noncompliant terrestrial substrates (walking on land) favor adaptations including emergence of intracellular architecture (changes in the cytoskeleton and upregulation of structural protein manufacture), inter-cellular con- densation, mineralization of tissues, and emergence of higher order architectures?How far does evolutionary Darwinism extend and how can we exploit this knowl- edge to engineer smart materials and architectures on Earth and new, exploratory environments?[Knothe Tate et al. 2008]. We are limited only by our ability to imagine. Ultimately, we aim to understand nature, mimic nature, guide nature and/or exploit nature’s engineering paradigms without engineer-ing ourselves out of existence.

Dimensions of coupling in middleware

It is well accepted that different types of distributed architectures require different degrees of coupling. For example, in client-server and three-tier architectures, application components are generally tightly coupled, both with one another and with the underlying middleware. Meanwhile, in off-line transaction processing, grid computing and mobile applications, the degree of coupling between application components and with the underlying middleware needs to be minimized. Terms such as ‘synchronous’, ‘asynchronous’, ‘blocking’, ‘non-blocking’, ‘directed’, and ‘non-directed’ are often used to refer to the degree of coupling required by an architecture or provided by a middleware. However, these terms are used with various connotations. Although various informal definitions have been provided, there is a lack of an overarching formal framework to unambiguously communicate architectural requirements with respect to (de-)coupling. This article addresses this gap by: (i) formally defining three dimensions of (de-)coupling; (ii) relating these dimensions to existing middleware; and (iii) proposing notational elements to represent various coupling integration patterns. This article also discusses a prototype that demonstrates the feasibility of its implementation.

Empirical research in business process management : introduction to the special issue

In this editorial letter, we provide the readers of Information Systems and e-Business Management with an introduction to Business Process Management and the challenges of empirical research in this field. We then briefly describe selected examples of current research efforts in this fields and how the papers accepted for this special issue contribute to extending our body of knowledge.

Exploiting the 1,2,3-triazolium motif in anion-templated formation of a bromide-selective rotaxane host assembly

Stimulated by the efficacy of copper (I) catalysed Huisgen-type 1,3-dipolar cycloaddition of terminal alkynes and organic azides to generate 1,4-disubstituted 1,2,3-triazole derivatives, the importance of ‘click’ chemistry in the synthesis of organic and biological molecular systems is ever increasing.[1] The mild reaction conditions have also led to this reaction gaining favour in the construction of interlocked molecular architectures.[2-4] In the majority of cases however, the triazole group simply serves as a covalent linkage with no function in the resulting organic molecular framework. More recently a renewed interest has been shown in the transition metal coordination chemistry of triazole ligands.[3, 5, 6] In addition novel aryl macrocyclic and acyclic triazole based oligomers have been shown to recognise halide anions via cooperative triazole C5-H….anion hydrogen bonds.[7] In light of this it is surprising the potential anion binding affinity of the positively charged triazolium motif has not, with one notable exception,[8] been investigated. With the objective of manipulating the unique topological cavities of mechanically bonded molecules for anion recognition purposes, we have developed general methods of using anions to template the formation of interpenetrated and interlocked structures.[9-13] Herein we report the first examples of exploiting the 1,2,3-triazolium group in the anion templated formation of pseudorotaxane and rotaxane assemblies. In an unprecedented discovery the bromide anion is shown to be a superior templating reagent to chloride in the synthesis of a novel triazolium axle containing [2]rotaxane. Furthermore the resulting rotaxane interlocked host system exhibits the rare selectivity preference for bromide over chloride...

Sulfate anion templation of macrocycles, capsules, interpenetrated and interlocked structures

This review examines the potential of anions, in particular sulfate, to template the formation of complex molecular architectures. Until recently, sulfate has been largely overlooked in this area and the examples described herein demonstrate this anion’s versatility in templating the formation of a diverse range of molecular systems including macrocycles, helixes, molecular capsules, interpenetrated and interlocked assemblies such as catenanes. In addition sulfate has been shown to template the formation of interpenetrated structures on a range of solid surfaces including gold, polystyrene beads and silicate nanoparticles, highlighting the potential of this anion in the fabrication of functional sensory devices exhibiting highly selective binding behaviour.

Towards a unified service description language for the internet of services : requirements and first developments

Service-oriented Architectures (SOA) and Web services leverage the technical value of solutions in the areas of distributed systems and cross-enterprise integration. The emergence of Internet marketplaces for business services is driving the need to describe services, not only from a technical level, but also from a business and operational perspective. While, SOA and Web services reside in an IT layer, organizations owing Internet marketplaces are requiring advertising and trading business services which reside in a business layer. As a result, the gap between business and IT needs to be closed. This paper presents USDL (Unified Service Description Language), a specification language to describe services from a business, operational and technical perspective. USDL plays a major role in the Internet of Services to describe tradable services which are advertised in electronic marketplaces. The language has been tested using two service marketplaces as use cases.

The rise of web service ecosystems

The convergence of Internet marketplaces and service-oriented architectures has spurred the growth of Web service ecosystems. This paper articulates a vision for Web service ecosystems, discusses early manifestations of this vision, and presents a unifying architecture to support the emergence of larger and more sophisticated ecosystems