Bone marrow-derived mesenchymal stem cells become anti-angiogenic when chondrogenically or osteogenically differentiated:implications for bone and cartilage tissue engineering

Osteochondral tissue repair requires formation of vascularized bone and avascular cartilage. Mesenchymal stem cells stimulate angiogenesis both in vitro and in vivo but it is not known if these proangiogenic properties change as a result of chondrogenic or osteogenic differentiation. We investigated the angiogenic/antiangiogenic properties of equine bone marrow-derived mesenchymal stem cells (eBMSCs) before and after differentiation in vitro. Conditioned media from chondrogenic and osteogenic cell pellets and undifferentiated cells was applied to endothelial tube formation assays using Matrigel™. Additionally, the cell secretome was analysed using LC-MS/MS mass spectrometry and screened for angiogenesis and neurogenesis-related factors using protein arrays. Endothelial tube-like formation was supported by conditioned media from undifferentiated eBMSCs. Conversely, chondrogenic and osteogenic conditioned media was antiangiogenic as shown by significantly decreased length of endothelial tube-like structures and degree of branching compared to controls. Undifferentiated cells produced higher levels of angiogenesis-related proteins compared to chondrogenic and osteogenic pellets. In summary, eBMSCs produce an array of angiogenesis-related proteins and support angiogenesis in vitro via a paracrine mechanism. However, when these cells are differentiated chondrogenically or osteogenically, they produce a soluble factor(s) that inhibits angiogenesis. With respect to osteochondral tissue engineering, this may be beneficial for avascular articular cartilage formation but unfavourable for bone formation where a vascularized tissue is desired. © Copyright 2014, Mary Ann Liebert, Inc.

Analysis of secretory, immunostaining and clinical characteristics of human "functionless" pituitary adenomas:transdifferentiation or gonadotropinomas?

In this study, the central technique of in vitro culture has been used to further investigate whether LH/FSH-expressing, but clinically "functionless" pituitary adenomas are gonadotropinomas or whether their hormone secretion is due to transdifferentiation events. 664 "functionless" pituitary adenomas were examined for hormone secretion by in vitro culture and for hormone content by immunostaining. The results were correlated with the clinical findings. 40% of the tumours (n = 263) secreted at least one of the gonadotropins alone, 8% (n = 53) exhibited various patterns of anterior pituitary hormones, whilst the remaining 52% of tumours were not associated with any hormone. In the secretory tumours, immunostaining revealed only a few scattered hormone-containing cells (5 to 15%). Mild hyperprolactinaemia was observed in some cases, presumably because of pressure effects of the tumours. The majority of the patients suffered clear cut hypopituitarism (p < 0.05). Pre-operatively, gonadotropin hypersecretion was observed in 3 cases, but only one of these secreted hormones in culture. Interestingly, a higher proportion of tumours removed from patients with hypopituitarism showed secretory activity in vitro than those tumours removed from patients showing no hormonal dysfunction or hyperprolactinaemia. We conclude that the term "gonadotropinoma" to describe functionless pituitary tumours associated with LH and/or FSH secretion is a misnomer, because the presence of LH and/or FSH confirmed by in vitro methods in the present series is a result of only a few scattered cells. We suggest that primary pituitary tumour cells differentiate into a secretory type (transdifferentiation), possibly in response to altered serum hormone levels such as decreased steroids. Further work is required to identify the factors which trigger the altered cells' characteristics. © J. A. Barth Verlag in Georg Thieme Verlag KG.

A techno-economic comparison of power production by biomass fast pyrolysis with gasification and combustion

This paper presents an assessment of the technical and economic performance of thermal processes to generate electricity from a wood chip feedstock by combustion, gasification and fast pyrolysis. The scope of the work begins with the delivery of a wood chip feedstock at a conversion plant and ends with the supply of electricity to the grid, incorporating wood chip preparation, thermal conversion, and electricity generation in dual fuel diesel engines. Net generating capacities of 1–20 MWe are evaluated. The techno-economic assessment is achieved through the development of a suite of models that are combined to give cost and performance data for the integrated system. The models include feed pretreatment, combustion, atmospheric and pressure gasification, fast pyrolysis with pyrolysis liquid storage and transport (an optional step in de-coupled systems) and diesel engine or turbine power generation. The models calculate system efficiencies, capital costs and production costs. An identical methodology is applied in the development of all the models so that all of the results are directly comparable. The electricity production costs have been calculated for 10th plant systems, indicating the costs that are achievable in the medium term after the high initial costs associated with novel technologies have reduced. The costs converge at the larger scale with the mean electricity price paid in the EU by a large consumer, and there is therefore potential for fast pyrolysis and diesel engine systems to sell electricity directly to large consumers or for on-site generation. However, competition will be fierce at all capacities since electricity production costs vary only slightly between the four biomass to electricity systems that are evaluated. Systems de-coupling is one way that the fast pyrolysis and diesel engine system can distinguish itself from the other conversion technologies. Evaluations in this work show that situations requiring several remote generators are much better served by a large fast pyrolysis plant that supplies fuel to de-coupled diesel engines than by constructing an entire close-coupled system at each generating site. Another advantage of de-coupling is that the fast pyrolysis conversion step and the diesel engine generation step can operate independently, with intermediate storage of the fast pyrolysis liquid fuel, increasing overall reliability. Peak load or seasonal power requirements would also benefit from de-coupling since a small fast pyrolysis plant could operate continuously to produce fuel that is stored for use in the engine on demand. Current electricity production costs for a fast pyrolysis and diesel engine system are 0.091/kWh at 1 MWe when learning effects are included. These systems are handicapped by the typical characteristics of a novel technology: high capital cost, high labour, and low reliability. As such the more established combustion and steam cycle produces lower cost electricity under current conditions. The fast pyrolysis and diesel engine system is a low capital cost option but it also suffers from relatively low system efficiency particularly at high capacities. This low efficiency is the result of a low conversion efficiency of feed energy into the pyrolysis liquid, because of the energy in the char by-product. A sensitivity analysis has highlighted the high impact on electricity production costs of the fast pyrolysis liquids yield. The liquids yield should be set realistically during design, and it should be maintained in practice by careful attention to plant operation and feed quality. Another problem is the high power consumption during feedstock grinding. Efficiencies may be enhanced in ablative fast pyrolysis which can tolerate a chipped feedstock. This has yet to be demonstrated at commercial scale. In summary, the fast pyrolysis and diesel engine system has great potential to generate electricity at a profit in the long term, and at a lower cost than any other biomass to electricity system at small scale. This future viability can only be achieved through the construction of early plant that could, in the short term, be more expensive than the combustion alternative. Profitability in the short term can best be achieved by exploiting niches in the market place and specific features of fast pyrolysis. These include: •countries or regions with fiscal incentives for renewable energy such as premium electricity prices or capital grants; •locations with high electricity prices so that electricity can be sold direct to large consumers or generated on-site by companies who wish to reduce their consumption from the grid; •waste disposal opportunities where feedstocks can attract a gate fee rather than incur a cost; •the ability to store fast pyrolysis liquids as a buffer against shutdowns or as a fuel for peak-load generating plant; •de-coupling opportunities where a large, single pyrolysis plant supplies fuel to several small and remote generators; •small-scale combined heat and power opportunities; •sales of the excess char, although a market has yet to be established for this by-product; and •potential co-production of speciality chemicals and fuel for power generation in fast pyrolysis systems.

The evolution of learning systems:to Bayes or not to be

Bayesian algorithms pose a limit to the performance learning algorithms can achieve. Natural selection should guide the evolution of information processing systems towards those limits. What can we learn from this evolution and what properties do the intermediate stages have? While this question is too general to permit any answer, progress can be made by restricting the class of information processing systems under study. We present analytical and numerical results for the evolution of on-line algorithms for learning from examples for neural network classifiers, which might include or not a hidden layer. The analytical results are obtained by solving a variational problem to determine the learning algorithm that leads to maximum generalization ability. Simulations using evolutionary programming, for programs that implement learning algorithms, confirm and expand the results. The principal result is not just that the evolution is towards a Bayesian limit. Indeed it is essentially reached. In addition we find that evolution is driven by the discovery of useful structures or combinations of variables and operators. In different runs the temporal order of the discovery of such combinations is unique. The main result is that combinations that signal the surprise brought by an example arise always before combinations that serve to gauge the performance of the learning algorithm. This latter structures can be used to implement annealing schedules. The temporal ordering can be understood analytically as well by doing the functional optimization in restricted functional spaces. We also show that there is data suggesting that the appearance of these traits also follows the same temporal ordering in biological systems. © 2006 American Institute of Physics.

Do educators need educating?

Actual text: I was recently at the Spanish College of Optometry biennial conference and attended a meeting of contact lens lecturers from around Spain and Portugal. We discussed various ideas, mainly about how to share good practice and improve standards. What came to my mind was ‘is there a blueprint for training trainers?’ Well probably not but there are many things that we need to acknowledge such as the way students learn for example. Many educators themselves were taught by lecturers who would write on a blackboard or use acetate on an overhead projector, then came the 35 mm slide era followed by the Powerpoint era. More recently there is a move towards a much more integrated approach of various teaching methods. At my university our contact lens and anterior eye lectures generally follow a format where a narrated Powerpoint lecture is uploaded onto our internal virtual learning environment. This narrated version of the slides is designed to give the didactic element of the topic. The students listen to that before attending an interactive seminar on that topic. The seminar is also recorded so that students can listen to that afterwards. The seminar is designed to give additional information, such as case reports, or to clarify key points or for live demonstrations. It is a good way of doubling the contact time with the students without imposing further on an already packed formal timetable as the students can work in their own time. One problem that we noticed with this approach was that attendance can vary. If the students feel that they will gain something from the interactive seminar then they are more likely to attend – exam tips usually win them over! At the Spanish meeting the educators decided that they wanted to have regular meetings. The industry colleagues in attendance said that they were happy to help but could not necessarily give money, but they could offer meeting rooms, pay for lunch and evening meals. They even said that that they were happy to host meetings and invite other companies too (except to manufacturing plants). In the UK the British Committee of Contact Lens Educators (BUCCLE) meets for one day on three occasions in the year. The American Optometric Contact Lens Educators (AOCLE) meets annually at a three day event. Both these organisations get some help from industry. BUCCLE usually has one of its meetings at a university, one at a company training centre/manufacturing plant/national headquarters and one meeting the day before the BCLA annual conference. BUCCLE usually has its pre-BCLA meeting in conjunction with the International Association of Contact Lens Educators (IACLE). So when educators meet what would they discuss; well probably the focus should be on education rather than actual contact lens knowledge. For example sharing ideas on how to teach toric lens fitting would be better than discussing the actual topic of toric lenses itself. Most universities will have an education department with an expert who could share ideas on how to use the internet in teaching or how to structure lectures or assessments etc. In the past I have helped with similar training programmes in other countries and sharing good practice in pedagogy is always a popular topic. Anyone who is involved in education in the field of contact lenses should look at the IACLE web page and look out for the IACLE World Congress in 2015 in the days preceding the BCLA. Finally, IACLE, AOCLE and BUCCLE all exist as a result of generous educational grants from contact lens companies and anyone interested in finding out more about should refer to their respective web pages.

A multi-modular second life hybrid battery energy storage system for utility grid applications

The modern grid system or the smart grid is likely to be populated with multiple distributed energy sources, e.g. wind power, PV power, Plug-in Electric Vehicle (PEV). It will also include a variety of linear and nonlinear loads. The intermittent nature of renewable energies like PV, wind turbine and increased penetration of Electric Vehicle (EV) makes the stable operation of utility grid system challenging. In order to ensure a stable operation of the utility grid system and to support smart grid functionalities such as, fault ride-through, frequency response, reactive power support, and mitigation of power quality issues, an energy storage system (ESS) could play an important role. A fast acting bidirectional energy storage system which can rapidly provide and absorb power and/or VARs for a sufficient time is a potentially valuable tool to support this functionality. Battery energy storage systems (BESS) are one of a range suitable energy storage system because it can provide and absorb power for sufficient time as well as able to respond reasonably fast. Conventional BESS already exist on the grid system are made up primarily of new batteries. The cost of these batteries can be high which makes most BESS an expensive solution. In order to assist moving towards a low carbon economy and to reduce battery cost this work aims to research the opportunities for the re-use of batteries after their primary use in low and ultra-low carbon vehicles (EV/HEV) on the electricity grid system. This research aims to develop a new generation of second life battery energy storage systems (SLBESS) which could interface to the low/medium voltage network to provide necessary grid support in a reliable and in cost-effective manner. The reliability/performance of these batteries is not clear, but is almost certainly worse than a new battery. Manufacturers indicate that a mixture of gradual degradation and sudden failure are both possible and failure mechanisms are likely to be related to how hard the batteries were driven inside the vehicle. There are several figures from a number of sources including the DECC (Department of Energy and Climate Control) and Arup and Cenex reports indicate anything from 70,000 to 2.6 million electric and hybrid vehicles on the road by 2020. Once the vehicle battery has degraded to around 70-80% of its capacity it is considered to be at the end of its first life application. This leaves capacity available for a second life at a much cheaper cost than a new BESS Assuming a battery capability of around 5-18kWhr (MHEV 5kWh - BEV 18kWh battery) and approximate 10 year life span, this equates to a projection of battery storage capability available for second life of >1GWhrs by 2025. Moreover, each vehicle manufacturer has different specifications for battery chemistry, number and arrangement of battery cells, capacity, voltage, size etc. To enable research and investment in this area and to maximize the remaining life of these batteries, one of the design challenges is to combine these hybrid batteries into a grid-tie converter where their different performance characteristics, and parameter variation can be catered for and a hot swapping mechanism is available so that as a battery ends it second life, it can be replaced without affecting the overall system operation. This integration of either single types of batteries with vastly different performance capability or a hybrid battery system to a grid-tie 3 energy storage system is different to currently existing work on battery energy storage systems (BESS) which deals with a single type of battery with common characteristics. This thesis addresses and solves the power electronic design challenges in integrating second life hybrid batteries into a grid-tie energy storage unit for the first time. This study details a suitable multi-modular power electronic converter and its various switching strategies which can integrate widely different batteries to a grid-tie inverter irrespective of their characteristics, voltage levels and reliability. The proposed converter provides a high efficiency, enhanced control flexibility and has the capability to operate in different operational modes from the input to output. Designing an appropriate control system for this kind of hybrid battery storage system is also important because of the variation of battery types, differences in characteristics and different levels of degradations. This thesis proposes a generalised distributed power sharing strategy based on weighting function aims to optimally use a set of hybrid batteries according to their relative characteristics while providing the necessary grid support by distributing the power between the batteries. The strategy is adaptive in nature and varies as the individual battery characteristics change in real time as a result of degradation for example. A suitable bidirectional distributed control strategy or a module independent control technique has been developed corresponding to each mode of operation of the proposed modular converter. Stability is an important consideration in control of all power converters and as such this thesis investigates the control stability of the multi-modular converter in detailed. Many controllers use PI/PID based techniques with fixed control parameters. However, this is not found to be suitable from a stability point-of-view. Issues of control stability using this controller type under one of the operating modes has led to the development of an alternative adaptive and nonlinear Lyapunov based control for the modular power converter. Finally, a detailed simulation and experimental validation of the proposed power converter operation, power sharing strategy, proposed control structures and control stability issue have been undertaken using a grid connected laboratory based multi-modular hybrid battery energy storage system prototype. The experimental validation has demonstrated the feasibility of this new energy storage system operation for use in future grid applications.

An exploration of pharmacy-specific reasons for non-adherence to prescribed medicines in a socioeconomically deprived, ethnically diverse UK cohort

Methods - Ethical approval for the study was granted by both the local National Health Service (NHS) Research Ethics Committee (REC) and Aston University’s REC. Seven focus groups were conducted between October and December 2011 in medical or community settings within inner-city Birmingham (UK). Discussions were guided by a theme plan which was developed from key themes identified by a literature review and piloted via a Patient Consultation Group. Each focus group had between 3 and 7 participants. The groups were digitally recorded and subsequently transcribed verbatim. The transcriptions were then subjected to thematic analysis via constant comparison in order to identify emerging themes. Results - Participants recognised the pharmacist as an expert source of advice about prescribed medicines, a source they frequently felt a need to consult as a result of the inadequate supply of medicines information from the prescriber. However, an emerging theme was a perception that pharmacists had an oblique profit motive relating to the supply of generic medicines with frequent changes to the ‘brand’ of generic supplied being attributed to profit-seeking by pharmacists. Such changes had a negative impact on the patient’s perceived efficacy of the therapy which may make non-adherence more likely. Conclusions - Whilst pharmacists were recognised as medicines experts, trust in the pharmacist was undermined by frequent changes to generic medicines. Such changes have the potential to adversely impact adherence levels. Further, quantitative research is recommended to examine if such views are generalisable to the wider population of Birmingham and to establish if such views impact on adherence levels.

Nationalism and globalisation:conflicting or complementary?

Nationalism and globalisation are two central phenomena of the modern world, that have both shaped and been shaped by each other, yet few connections have been made systematically between the two. This book brings together leading international scholars to examine the effect of globalisation on nationalism, and how the persistence of the nation affects globalisation. With a range of case studies from Europe, the US and Asia, the authors focus on the interaction between globalisation, national identity, national sovereignty, state-formation and the economy. ◦ Part one provides theoretical reflections on the flexibility and plasticity of the terms nationalism and globalisation focusing on the ways in which nationalism has shaped and has been shaped by globalising forces. ◦ Part two examines the relationship between nationalism and globalisation in different historical eras and different regions, questioning established approaches. ◦ Part three focuses on contemporary issues including the economic crisis, labour migration and citizenship and the theme of global culture. The result is a highly topical account that considers the conceptual landscape of Nationalism and Globalisation. With an interdisciplinary approach, Nationalism and Globalisation will be of interest to students and scholars of political science, sociology, history, economics and international relations.

Sharing of value in business relationships:a theoretical model

This paper explores the sharing of value in business transactions. Although there is an increased usage of the terminology of value in marketing (such concepts as value based selling and pricing), as well as in purchasing (value-based purchasing), the definition of the term is still vague. In order to better understand the definition of value, the author’s argue that it is important to understand the sharing of value, in general and the element of power for the sharing of value in particular. The aim of this paper is to add to this debate and this requires us to critique the current models. The key process that the analysis of power will help to explain is the division of the available revenue stream flowing up the chain from the buyer's customers. If the buyer and supplier do not cooperate, then power will be key in the sharing of that money flow. If buyers and suppliers fully cooperate, they may be able to reduce their costs and/or increase the quality of the sales offering the buyer makes to their customer.

Control of cascaded DC-DC converter-based hybrid battery energy storage systems - Part I:stability Issue

There is an emerging application which uses a mixture of batteries within an energy storage system. These hybrid battery solutions may contain different battery types. A DC-side cascaded boost converters along with a module based distributed power sharing strategy has been proposed to cope with variations in battery parameters such as, state-of-charge and/or capacity. This power sharing strategy distributes the total power among the different battery modules according to these battery parameters. Each module controller consists of an outer voltage loop with an inner current loop where the desired control reference for each control loop needs to be dynamically varied according to battery parameters to undertake this sharing. As a result, the designed control bandwidth or stability margin of each module control loop may vary in a wide range which can cause a stability problem within the cascaded converter. This paper reports such a unique issue and thoroughly investigates the stability of the modular converter under the distributed sharing scheme. The paper shows that a cascaded PI control loop approach cannot guarantee the system stability throughout the operating conditions. A detailed analysis of the stability issue and the limitations of the conventional approach are highlighted. Finally in-depth experimental results are presented to prove the stability issue using a modular hybrid battery energy storage system prototype under various operating conditions.

Four-leg converters with improved common current sharing and selective voltage-quality enhancement for islanded microgrids

Four-leg dc-ac power converters are widely used for the power grids to manage grid voltage unbalance caused by the interconnection of single-phase or three-phase unbalanced loads. These converters can further be connected in parallel to increase the overall power rating. The control of these converters poses a particular challenge if they are placed far apart with no links between them (e.g., in islanded microgrids). This challenge is studied in this paper with each four-leg converter designed to have improved common current sharing and selective voltage-quality enhancement. The common current sharing, including zero sequence component, is necessary since loads are spread over the microgrid and they are hence the common responsibility of all converters. The voltage-quality enhancement consideration should however be more selective since different loads have different sensitivity levels towards voltage disturbances. Converters connected to the more sensitive load buses should therefore be selectively triggered for compensation when voltage unbalances at their protected buses exceed the predefined thresholds. The proposed scheme is therefore different from conventional centralized schemes protecting only a common bus. Simulation and experimental results obtained have verified the effectiveness of the proposed scheme when applied to a four-wire islanded microgrid.