Griffiths Et Al for Publication

7/31/2019 Griffiths Et Al for Publication

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Conceptual Design of a Cutting Edge Stem Cell Research

Facility

Thomas Griffiths, Andrew Peto, Joseph Thorogood, Daniel Tiffany, Oliver

Michalakis, School of Mechanical Engineering, Faculty of Engineering

ABSTRACT

A team of three mechanical engineers and two product designers carried out a

conceptual design of a stem cell research facility for AstraZeneca. The project has

been approached systematically based on concurrent engineering principles and

popular design methodology. An innovative design incorporated with energy efficient

features and sustainable practices is presented that meets the core process

requirements. The efficiency of the work process has been optimised through

applying lean principles to reduce the work travel around the laboratory and

incorporating electronic tracking systems. An automation system is presented that

improves the consistency and quality of research, as well as increasing

productivity at a lower cost than by employing more scientists. Energy efficient

strategies have been implemented that lower the energy base load and increase

energy efficiency in key areas such as HVAC and lighting. A key limitation of the

project was the fact that it was carried out by a small team of individuals with noprevious biological sciences or civil engineering experience, therefore a natural

progression of the study would be to have the design evaluated by specialists in

these subject areas.

Keywords: Stem cell; research facility; conceptual design.


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Conceptual Design of a Cutting Edge Stem Cell ResearchFacility

INTRODUCTIONHuman stem cells are unique in their ability to self renew and when given the rightsignals, to differentiate into various other cells of the human body [1, 2]. Millionsof people throughout the world who suffer from degenerative diseases couldpotentially benefit from treatments derived from them; specialised cells such asmuscle or bone cells could be cultured in the laboratory to replace diseased organsor tissues within the human body [3]. Furthermore, it is hoped that stem cells can beused as screening tools in the testing of prospective drugs, aiding the discovery ofnew treatments [4]. With such huge potential, AstraZeneca has identified stem celltechnology as a key strategic area of research for the future. As such, AstraZeneca,one of the worlds leading pharmaceutical companies, set this project the challengeof creating a conceptual design of a stem cell research facility that focused on leandesign, automation, energy efficiency, sustainability and innovation. As a

multidisciplinary team of three Mechanical Engineers and two Product Designers,this project aims to design a cutting edge stem cell research facility of the future.By not having either a bioscience background or experience of working in such alaboratory, the team has the ability to start from scratch and offer new, freshopinions without the constraints of current practices.

Under the direction of a project brief set out by AstraZeneca, the objectives are todesign a facility that is creative, innovative, sustainable and energy efficient. Inaddition, the efficiency, quality and productivity of research will be optimisedthrough applying lean principles to the design of the facility and investigating theuse of state of the art automation and electronic systems.

STATE OF THE ART LITERATURE REVIEWThe Good Laboratory Practice Regulations 1999 revealed many importantstandard operating procedures that were taken into account in the final conceptualdesign of the laboratory. Some of the important points in this paper include storageand tracking regulations, containment and the requirements of a scientists workingarea [5, 6].

Work Flow and Lean PrinciplesLean principles are modern techniques applied to manufacturing methods in orderto increase productivity and profit. Lean ideology revolves around five leanprinciples which are stated by Womack and Jones as specifying value, identifyingvalue stream, flow, pull and perfection [8]. Womack and Jones also state that everyaction that takes place in a production process can be classified as value adding,non-value adding but unavoidable, and non- value adding and removable [9]. Eachaction should be assigned to one of these groups and dealt with accordingly [10]. Amajor part of lean thinking is the removal of Muda or waste, this occurs heavily in thenon-value adding categories of action. The seven signs of waste detailed by Bichenoare; overproduction, waiting, transporting, inappropriate processing, unnecessaryinventory, unnecessary motions and defects; the aim of any lean manufacturingprocess is to remove this waste. This can be done through various lean tools suchas CANDO; a method for arranging and optimising the immediate workspace [10].

Joseph has conducted a study with the aim of applying lean principles to a

laboratory environment [11]. The study focused on four of the seven types of Mudathat Joseph deemed applicable namely; waiting for work, unnecessary transport,unnecessary movement by staff and excessive inventory. The paper stated that


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the first stages in creating a lean laboratory design are: understanding the workflow,measuring the process times, and analysing the specimen arrival times andworkload each day. The paper also revealed that the most important document toproduce in the early stages is a value stream map [11].

Automation & TrackingCell culture is conventionally a highly laborious, repetitive process that requirescareful preparation and adherence to the correct procedures to maintain sterility [12,13]. As an ongoing process it is also not ideally suited to the Monday to Fridayschedule of scientists, which can lead to lag times due to cells not being tended toover the weekend. Automation can operate 24 hours a day 7 days a week,continuously tend to the cells and schedule them to be ready for experiments at theright time [12-14]. Significant increases in productivity through the use of laboratoryautomation have been seen in numerous studies [14-16]. Another key benefitis a level of standardisation and consistency in the process that scientists cannotachieve. Humans are prone to tiredness, mistakes and carrying out processesslightly differently to each other, whereas automation does not have these

weaknesses [12]. Thomas et al[16] describe how automation can be used in theapplication of Six Sigma methodology by identifying and reducing processvariation in order to improve the quality of research. Automation can range froma simple loading robotic arm used to move samples from one place to another, tolarge scale integrated systems that perform multiple stages of the cell cultureprocess. It also allows scientists to focus more attention on activities that requirethought and creativity, by performing the pre-determined routine tasks for them.

Closely linked to automation is the potential for electronic systems in the accurateand efficient tracking of samples around the laboratory. Common practice for manylabs is to use a manual handwritten system for doing this, which is outdated,inefficient and has a higher potential for mistakes. Great success has been seen

using either barcode or RFID label systems instead [15-17], which have theadvantages of being faster, more efficient and reduce the likelihood of mistakes. It isfelt that a barcode system is the most advantageous in this case, as it is cheaperthan RFID and more easily integrated with various automation machines. Liquidnitrogen storage is an important part of the cell culture process and RFID has thedisadvantage of not being able to function in the inevitable cold temperatures of thisstorage technique, whereas barcode labels can [18].

Design innovationDesign innovation can aid the functionality and working environment of the researchfacility. It is suggested that designers should develop tactical techniques of designthat work around the occupants rather than provide them with a design to work in[19]. Leon has outlined the importance of innovation in design to promoteknowledge transfer, collaboration and a flexible yet simple working environmentwhich can increase productivity [20]. Innovative working environments can fostercreativity and increase productivity which some of the worlds leading companiesare exploiting with modern, green and wacky designs [19, 21-25].

The development of smart materials and products have been incorporated intooffices to improve the aesthetics and increase productivity. Examples include smartglass and a sky factory which projects environmental scenes to change the workingenvironment to suit a users preferences [26, 27]. Ideas paint is a unique way to usesurfaces to generate ideas, particularly in informal areas [28]. Another interesting

technology is a projector system called Light Blue that can project an image onto asurface which a user can then interact with [29]. E-readers and tablet computers arean excellent way to share and process information for users who change locations


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frequently. Finally touch-down pods provide a private workspace free fromdistractions that allow users to work if they are away from their office [21].

ContainmentContainment within the laboratory is a high priority and is categorised into four

bio safety levels (BSL). AstraZenecas current research facility operates at BSL-2which must have certain features to provide an acceptable level of safety. Accessto the laboratory must be through an air-locked access room. Floors must bemonolithic, slip resistant, and easy to clean and decontaminate. Benches andcabinets need to be sealed to the floor and walls, and regularly decontaminated[30]. Sinks located by disposal areas and exits must be hands free [31].

Airflow through the laboratory requires a ducted air ventilation system. This suppliesclean air into the laboratory and removes contaminated air via an exhaust duct.Exhaust air must not be re-circulated back into the laboratory; instead it must bevented away from air intakes and filtered through a HEPA (High efficiencyparticulate air) filter to prevent contaminated air being supplied back into the

laboratory. The air from Class II BSC cabinets can be filtered back into the lab usinga HEPA filter if the cabinet has been tested and clarified [30].

Energy EfficiencyLaboratories consume significant amounts of energy due to poor design,intensive equipment and strictly controlled environments. It has been found thatlaboratories consume four to six times more energy per square foot than a typicaloffice, and a single six-foot wide hood consumes as much energy as three timesthe average U.S. home [32, 33]. With better design and implementation of energysaving features it is possible to make energy savings of approximately 20-60% within alaboratory and 50-75% within a typical building [32-34]. This can be accomplishedthrough natural, passive and mechanical strategies such as daylighting, solar

management, thermal mass, natural ventilation, insulation, co- and tri-generation,ground source heat pumps and heat recovery which have all been shown to reduceenergy consumption [35-37, 38, 39]. Energy delivery is another opportunity forenergy savings such as under-floor heating, chilled ceilings and displacementventilation which can all reduce energy with the latter two shown to reduce energyconsumption within a laboratory by 57% [40, 41].

SustainabilityThe triple bottom line proposed by Elkington which was integrated into buildingdesign by McLennan and Mumovic explored environmental, economic and socialconsiderations; the three elements of sustainable design [42-44]. Social factorsinclude non-exploitation of people and businesses, safe working environments andcontribution to the local community. Economic factors are considerations such aspositive economic impact in the community and environmental impact in relation toeconomic investment. Environmental issues such as energy consumption, carbonfootprint, recycling and reuse of materials are also factors to consider.

Green roofing offers many benefits over conventional roofing such as a 90%reduction in water run-off, increased longevity and a positive impact on the local wildlife[45, 46]. A variety of grey water systems that reuse wastewater produced within thebuilding were explored and analysed as a potential sustainable system that couldbe integrated into the plumbing system of the facility [47].

METHODSThe systematic approach to a conceptual design, illustrated by Figure 1, was


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followed throughout the project. This is based on the recommendations of Pahl et al[7]. The approach is iterative in nature to encourage constant updating andimprovement.

Figure 1: The methodology followed throughout the project

Research MethodsResearch consisted of primary and secondary sources which were gathered inseveral ways. Early on in the project the team arranged a visit to the AstraZenecafacility at Alderley Park near Manchester which enabled the team to get a betterunderstanding of how cell research is conducted. Other research methodsincluded shadowing and filming a scientist in the University of Leeds biologylaboratory during a cell culture process and analysing the footage;submitting a questionnaire to several of the scientists at AstraZeneca, reviewingliterature such as books, journals, case studies, online articles, televisiondocumentaries (eg. BBC, Horizon Fix Me), and maintaining discussions withacademic staff and the AstraZeneca mentors.

Concurrent EngineeringIt was decided that the research and design stages would be approached usingconcurrent or simultaneous engineering methodology. This approach runs tasks inparallel which prevents over the wall engineering and reducesdevelopment time [7, 48]. This resulted in each team member taking responsibility foran aspect of the project to research, followed by the group coming together for

the final conceptual design.


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Design DevelopmentThe facility design went through a series of development stages after the individualresearch was performed. Initially each team member created a series of sketchesbased on their sub-functions from the work breakdown structure. Whilst these werenot evaluated it provided the group with approximately 20 designs to look at and

exchange ideas for further designs. The group came together to discuss whichrooms would be needed for the final design. Each team member then created onedesign that included all of the required rooms. Before these were evaluated, a set ofcriteria were established based on the most important aspects of the individualresearch. A decision matrix that encompassed these criteria was then used toevaluate each design which led to two successful designs. Further evaluation wasperformed on the final two designs to incorporate the best features of both; this led toa compromised design that merged creativity with function. This design wasiteratively improved to satisfy the requirements of the individual areas.

RESULTSAutomation & Tracking

It was determined through an extensive study that two CompacT SelecTs areequivalent to about six full time research scientists when running at full capacity.Figure 2 shows the cumulative cost of this automation system over an eight yearperiod, including all maintenance and running costs. It also shows the cumulativecost of funding scientists if they were to do the same amount of work manually. Thecost of a research scientist was based on an average figure of 137000 per year, assuggested by Sparey [49]. This also includes all hiring, training and facilities costsfor housing the scientist.

Figure 2: Automation cost projections

Figure 3 shows the layout of the automation system as it will be in thelaboratory. It can automate the entire cell splitting, plating and screeningprocesses in the lab, based on specified throughput rates. With effectively twolines working in parallel, if one machine breaks down the system would still be ableto process cells, albeit at a slower rate.

Thermo Fisher automated Microwell plate incubators (Cytomat 24C), plate

moving robots (Catalyst Express) and plate readers (Arrayscan) were chosen asthey meet the necessary work process and capacity requirements and can be easily


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integrated to work and communicate with each other. The Cytomat incubators hold504 Microwell plates each and have internal barcode scanners. This means platescan also be automatically tracked, scheduled, and moved in and out of the incubatorautomatically through communication with the moving robot. The screeningprocess can therefore be scheduled to run completely unattended at any time of theday.

Figure 3: The final automation layout

Tracking System DesignFigure 4 illustrates the tracking system design. Data is quickly and securely stored

in a central server and accessed via personal touch screen devices. A backupserver and uninterruptable power supplies have been included in case the mainserver should fail or there is a power outage. By using a personal touch screenwith onboard barcode scanning facilities, unnecessary travel between the laboratoryand office is cut down. Higher standards of quality are also achieved through thereduction of mistakes. The Pansonic Toughbook CF-H1 was chosen as thehandheld device for the following reasons:

It is built specifically for use in a healthcare/sterile environment. It is impact, water and chemical resistant and can be sterilised with ethanol.

It has built in barcode and RFID readers and is WIFI enabled.


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Figure 4: The final tracking system design

Lean PrinciplesAfter conducting a detailed analysis of the work processes undertaken in thelaboratory, it was decided to structure the laboratory as a production line. This was

to minimise the work travel and to simplify the work flow. The laboratory is laid out inorder of the processes that are carried out on the cells. The cells life in the laboratorygoes from storage, to resurrection, culturing and finally testing; therefore thelaboratory is laid out in this order. This means that the majority of the work flow willbe in one direction, leading to less complication and an increased understanding ofthe stage that each flask is at. Figure 5 shows the final layout.

Figure 5: The final laboratory layout

By analysing the work processes, the equipment for each section could beallocated. This leads to less travelling distance to the equipment as each


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appliance can be placed closer to the section in which it is u sed mos tf r eque nt l y . Disposables can also be kept in the immediate workspace of thesections in which they are used. Fi gu re 6 sh ow s ho w th e resurrection work spacewill be laid out.

Figure 6: The resurrection workspace area design

Innovation The office space is large and open plan which offers flexibility for long term

adaptation to changing working requirements.

Each scientist has their own ergonomic workspace. The office over-looks the laboratory for greater worker awareness.

There are several informal areas where staff can present and exchange ideas forgreater knowledge transfer.

Work pods have been provided to offer staff areas away from the office that arerelaxing and free from distractions.

On the second floor there is an informal team meeting area which can be used formorning briefings.

The work pods and the team area utilise smart glass that can provide differentenvironments to suit users preferences.

Energy Efficiency and SustainabilityLow Energy and Sustainable Design

The building has been orientated so that the glazed and open areas of thebuilding catch the maximum sunlight for lighting and solar heating.

Thermal mass has been used to dampen temperature swings within the internalenvironment and increase the lag time between external and internal changes.

Large amounts of thermal insulation have been used and advanced windowshave been incorporated to reduce fabric heat transfer by 42% compared to thebuilding regulations. Concrete and cellulose were chosen as they are highlysustainable, recyclable and have good thermal properties. Limestone whilst notas sustainable as concrete provides better aesthetics which are vital to thedesign.

A green roof has been employed to retain heat in the winter and cool the buildingin the summer. It also reduces the carbon footprint of the building, extends the lifeexpectancy of the roof membrane and has a positive impact on local wildlife.

The front of the building contains a large open volume with an atrium to induce

natural ventilation. Large amounts of south facing glazing have been used to provide daylight and


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solar heating. External shading has been applied to reduce summer, and maximise winter

solar heat gains. Light tunnels which provide over ten times the light intensity as a 100 watt bulb

have been incorporated to allow more natural light to enter the building to reduce

dependence on artificial lighting and provide social benefit. A short retention grey water system would be suitable for the facility. The system

would recycle waste water from showers and sinks for applications such asflushing toilets.

Waterless urinals that use a non-toxic chemical are to be installed in the building toreduce the amount of waste water produced within the building.

Low volatile organic chemicals (VOCs) and non-toxic paints are used throughoutthe building to ensure a safe working environment and minimal ecological impact.

Recycled rubber decking made from recycled plastic and wood fibres is used forany external walkways and recreational areas as it is highly durable, low cost andlow maintenance.

HVAC The base load for heating and cooling is supplied by a tri-generation system that

generates electricity, and uses the waste heat to provide heating, and utilises anabsorption chiller for cooling; it has been shown to achieve efficiencies of around80-90%.

The remaining heating and cooling is supplied by a ground source heat pumpwhich can achieve efficiencies greater than 80%.

The heating is delivered by an under-floor heating system and the cooling viaa chilled ceiling; both technologies can reduce energy consumption due toeffective heat transfer.

The ventilation uses a displacement system that can achieve an effectiveness

rating of over 100% and save energy by reducing fan and pump speed, and byrecovering up to 92% of heat. Night-time ventilation is used to dissipate built up heat that is stored in the

building.

Lighting

Energy efficient lamps are used and located so that the ambient level of lightingcan be at an appropriate level for the required task and then task lights aresupplied for dedicated tasks.

A control system uses photosensitive and occupancy sensors to adjust the lightlevels accordingly.

Final DesignThe final design of the facility conveys both function and form; achieved by thepractical floor plan coupled with the staggered effect and smooth curves of thebuilding design. The practicality of the facility is achieved by applying leanprinciples to the layout. The storage room and delivery areas are central to theimportant areas of the building, minimising the distance between it and thelaboratory, office and canteen. The work flow into the facility is optimised as thestorage lift is located within the delivery area and provides a direct route to thelaboratory; this is vital for the delivery of liquid nitrogen. A rear entrance to the liquidnitrogen room was deemed impractical due to containment issues however it wouldhave an emergency exit with escape stairs to the outside. The kill tanks are locatedin the basement underneath the laboratory for effective waste sterilisation. Thebasement also contains bike storage, showers, an autoclave and a generator, theformer two to encourage cycling to work and the latter two due to the noise they


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produce. Visibility throughout the facility and especially between the laboratoryand office was maximised to increase staff awareness and reduce wasted travelsearching for colleagues. This was achieved by having the office located above thelaboratory looking over it through a glass screen. The office, laboratory andrecreational areas were also open plan to help achieve this. There is a lecturetheatre that has been placed on the ground floor at the front of the facility for externalguests and speakers. Light tunnels have been placed on the roof so that most ofthe top floor and the laboratory contain large amounts of natural light for improvedwell being and increased productivity.

The building design is creative and attractive due to the staggered floor effect thatwas employed in the design. The curved footprint of the facility also adds to theaesthetics. Balconies created by the staggered effect act as areas in which workcan be escaped from and creativity can be enhanced. The atrium at the front ofprovides a grand entrance to the building that is well lit with open spaces. Largewindows throughout the building produce an interior that is flooded with natural light aswell as an improved exterior. The interior of the facility includes many modern features

that encourage creativity and increase productivity; the work pods located aroundthe facility provide individual work areas to encourage focus. The circular meetingarea on the second floor provides an accessible location for informal meetings withthe aid of boards and projectors, more informal meeting and recreational areas arealso located throughout the facility.

Figure 7: The final design of the research facility


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DISCUSSIONLimitationsThe project has several limitations which were mainly due to a lack of resourcesand inexperience in civil engineering and biology. The lack of resources meantthat the scope of the work was limited and not all aspects of the design

coul d be cov ered comprehensively. Examples include lean processesrevolving around consumables management in the delivery area and afeasibility study of renewable energy. Computer modelling was not viable due tothe time and expertise required to obtain an acceptable w or ki ng kn ow led gein so ft wa re pa ck ag es , consequently the energy analysis used peak and meanvalues instead of energy changes with respect to time. Much of the research wassecondary and then applied to the current and proposed facilities whichchallenges the validity of applying it to the proposed design. The inability toperform trials and create prototypes meant that some of the expected benefits offeatures such as light tunnels, work pods and automation cannot be confirmed.

Figure 8: Exploded view of the facility

RecommendationsIt is recommended that a team of experts complete a full review of this report anduse it as a starting point to perform further work. The scope of the project can beincreased to include a feasibility study of renewable energy, structural loadings,and operations and logistics management. It is also suggested that prototypes arecreated and trials performed within the current facility so that performance can bemore accurately evaluated and the risk through change over can be minimised. Anenergy audit of the current facility and computer modelling would provide muchmore accurate data with which to plan an energy efficiency strategy and henceminimise energy consumption. Finally it is recommended that a simulation of workprocesses is performed with potential problems such as excess deliveries, powercuts or equipment maintenance so that the productivity can be optimised for mosteventualities.


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CONCLUSIONSThe aim of the project was to create a conceptual design of a stem cell researchfacility for AstraZeneca that focused on lean design, automation, energy efficiency,sustainability and innovation. The team achieved this by following a project structurelaid out by Pahl et al[7]. A 3D CAD model of the facility was produced to display

this design.

The lean study mainly considered the design of the research laboratory, but alsotook into account other aspects of the facility. A map of the work processeshighlighted key areas of muda, these were eliminated by the application of newtechnologies. A work travel analysis was conducted and from this the generallaboratory layout was produced with minimal travel distance. The immediateworkspace of a scientist in the laboratory was designed with the most frequentlyused equipment located in the easiest to access locations.

Over an eight year life cycle the recommended automation system is expected todeliver a ROI of around 300%. Furthermore it improves the standardisation of the cell

culture process and therefore works towards higher standards of quality and fewererrors. Barcode tracking was also employed in the facility to reduce process timesand the risk of human error. The barcode system will be linked to a series ofhandheld devices carried by each scientist. These will also improve the sharing ofwork around the facility and the communication between the staff on a local andglobal scale. The tracking system can also be exploited as a system to pullconsumables into the laboratory; monitor stock levels and reduce unnecessaryinventory.

The improved thermal performance of the fabric using improved insulation, a greenroof and advanced windows has reduced heat transfer by 42%. A ground sourceheat pump and trigeneration system for heating, cooling and electricity generation

has been employed that has been shown to achieve efficiencies of around 80-90%compared to conventional systems that are only 30-40% efficient. A chilled ceiling,under-floor heating and displacement ventilation have been chosen because theyare more effective than traditional delivery methods and hence can reduce energyuse considerably. Furthermore the ventilation system is able to recover 92% ofheat. Finally solar management, utilisation of natural light, light control and energystorage strategies have been incorporated to reduce dependence on electrical andmechanical systems.

Several aspects of sustainability have been designed into the building such as highlyrecyclable materials, non toxic paints, low volatile chemicals, a grey water systemand waterless urinals. These features lower global energy consumption andpreserve natural resources for future generations.

Innovative design within the facility has created areas of transparency, creativity,knowledge and communication which is designed to enhance productivity andmorale throughout the facility. These are conveyed in the form of the work pods,think tanks, balconies and glass partitions.

The design of this research facility has considered the future requirements for stemcell research so that AstraZeneca can discover effective treatments at reducedcosts and time to market, thereby passing the benefits onto the consumer.


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ACKNOWLEDGMENTSThe authors would like to thank the project supervisors: Dr P.Walker, Dr J. Tipperand Dr S. Korossis for everything they did throughout the project and the guidancethat they provided. The staff at AstraZeneca were extremely helpful and providedguidance and opinion whenever it was needed, especially Leo Pickford and RyanHicks who oversaw the project. Thanks are also due to Dr I.Papageorgiou forallowing his work to be observed at the University of Leeds.

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