Cafe Scientific, Southampton, UK, past talks

Latest update of this file 08 Sept , 2018

Some details on past SWA science cafe talks in 2010 , including transcripts of talks and Q&A
Some details on SWA science cafe talks of later 2011
Some details on SWA science cafe talks of early 2011
Some details on SWA science cafe talks of early 2012
Some details on SWA science cafe talks of mid 2012
Some details on SWA science cafe talks of end 2012, including transcripts of talks and Q&A
Some details on SWA science cafe talks of early 2013, including transcripts of talks and Q&A
Some details on SWA science cafe talks of mid 2013, including transcripts of talks and Q&A
Some details on SWA science cafe talks of late 2013, including transcripts of talks and Q&A
Some details on SWA science cafe talks of early 2014, including transcripts of talks and Q&A
Some details on SWA science cafe talks of mid 2014, including transcripts of talks and Q&A
Some details on SWA science cafe talks of end 2014, including transcripts of talks and Q&A
Some details on SWA science cafe talks of early 2015, including transcripts of talks and Q&A
Some details on SWA science cafe talks of mid 2015, including transcripts of talks and Q&A
Some details on SWA science cafe talks of end 2015, including transcripts of talks and Q&A
Some details on SWA science cafe talks of early 2016, including transcripts of talks and Q&A
Some details on SWA science cafe talks of mid 2016, including transcripts of talks and Q&A
Some details on SWA science cafe talks of end 2016, including transcripts of talks and Q&A
Some details on SWA science cafe talks of early 2017, including transcripts of talks and Q&A
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Some summaries etc of past talks held at the venue, The Southwestern Arms (upstairs room) , 36 Adelaide Rd, St Denys, and St Denys Community Centre
Some hosts are not alowing remote linking now , so to view a "forbidden" picture you have to right click on the mouse and select "view". Not verbatim, and there will be homonyms, transcription, transliteration, typing and spelling errors and misattributions in the following write-ups, and also untranscribed potential litigious stuff that sometimes emerges. Q&A , grouped under one "Q" or ? terminator tend to be dialogue with / multiple questions from one enquirer. ? for unheard / masked words , ??? for phrases.

08 January 2018 , Simon Protheroe , Hampshire County Council : Highway Maintainence, , an overview. 19 people, 2 hours I'm a highways engineer with Hampshire Highways dept. I'p part of the routine maintainence group, reactive maintainence, we get the pot hole treports, issues with vegetation , flooding and drainage. We're the eyes on te ground to resolve any issues that occur. History of this starts from tackways that have bev=come such by ueage. A lot of our current highways have evolved through this pre-existing structure. The Romans were the first to introduce a full , proper highway layout, with a proper construction matrix and plans. A pic of a Roman road, doing well considering its age, Sian Helen ? in South Wales. The Highways Act of 1555 introduced the rights of a person to pass without hindrance over a piece of land. That is the definition of an English highway, common-law definition , not qritten down anywhere but it is enacted by law. In 1555 every Parish was enabled to have 2 highway surveyors, which over 4 days each year, between Easter and 24 June had to oversee the entire parish workforce, fit and able-bodied , men women and children to do HM. The parishes were responsible for all the highways within their parish, whether major trunk road beetween towns or just a local trackway. The parishes had no resource and very little power or money to do this maintsinence. So lobbying was done for turnpikes, toll roads that enabled small companies to be set up , to pay a toll to, to do this HM. Only 3 or 4 miles a time, rare a turnpike corporation would have 20 miles at the very maximum. Over the course of 150 years, turnpikes were the only way to be maintained. This only applied to the major link roads and some arterial routes around places like London. In 1888 The Local Government Act, counties would take HM off the parishes. Also applied to districts and burroughs, that has remained such. Roman Paving , the foundation is made of large boulders, designed not to fit together, includes lots of voids, allowing the roadbase to drain water away. Smaller layer of compacted stone, higher up , that are impermeable. They are protested by a layer of flagstones on top. Roman paving was constructed well and does survive well. It did require maintainence and when the romans left, many roads fell into disrepair. THomas Telford had an original idea, he introduced capstones at the bottom, to protect the ground formation . 20cm or so diameter and placed vertically , paked closely, to form the foundation. Then coarser stones, smaller plced over and compacted down . Then a surface coarse of 5cm stone, embedded into the road top. Telford recognised that drainage was key. Having a dry road means you;ll have a stable road and a strong road. If you have a wet road it will deteriorate and disintegrate very quickly. A lot of HM is dependent on keeping your roads dry. Macadam and macadamising is the main process adopted for the turnpikes, 1807 to 1870. Macadam felt there was no need for foundation stones att he base of the road, that well=sized and well-sorted stones of approx 5 to 10 cm laid together and well compacted, there was no need for the base as the loading would be evenly distributed to the grund. Macadams roads also required being dry, including drainage ditches. He introduced a camber to the road, for water to flow away . The French had a go at making wonderful roads, a man called Tragorstd. Unfortunately he failed to recognise the importance of drainage. He insisted his roads were trenched like the sunken lanes of the British countryside. This created nightmares for his lengthsmen to maintain. The stones were chipped by hand, the work parish children would have done along wiht the women. Men would have transported and l;aid the stone, spreading evenly across. Part of the Highways act allowed the surveyors , of each parish, to mine or quarry stone and gravel from local pits without hindrance. However they had to do this fairly. The later act of 1662, introduced penalties , fines on these surveyors if deriliction of duty was found, ie taking bribes or not doing a good job of it. A lot of responsibility was laid on them in htis later act. These days its easy to get grsaded stone, done by machine. A lot of thought went into the highways acts, into wheel sizes and diameters of wheels as it was found that skinny wheeled carts would dig in and rut the surface. Breaking it up a lot more quickly than a wider wheeled wagon. So a width of wheel was demanded and this was adopted throughout the UK. The Highways Act 1980, our bible, we work from stil ltoday. Supported by some other acts. THere are a few types of modern road construction. mostly a stone-base course, made of grade1 graded aggregate, 75mm in size. Then a surface course, including a binder coarse under it. The surface coarse is the road strength, takin gthe compressio nforce of passing vehicles. The typical road surface today is called ashphalt-concrete. A generic term for any bitumous make-up that has stones within it. There is an amount of sand content, an amount of stone content, and bitumin content. Bitumen content is typically no mor ethan 10%. It is designed to fill and bind the stones which may or may not be pre-coated with bitumen. The idea behind good road construction is you don't want voids. Voids create weakness, when pressure is placed upon them , the force can transfer thru these voids. Hot-rolled ashphalt is a more sand derrived AC wiht a high pecentage of sand, something like 70%, meaning its heavily compacted. When laying hot-rolled ashphalt, its laid out from the machine , then a series of coated chippings ,about 20mm are evenly dispersed , pressed and rolled into the surface. This is our preferred surface as H engineers. Its one of the most durable , strongest st and resistant surfaces we have in our arsenal. In some places it can look terrible, but is still retaing its strength because of its densly compacted nature. The fine matrix makes it very water-proof, very few void sp[aces within it. Stone mastic ashphalt is slightly different because it includes within it, fibres, very effective at finding and keeping the strain and stresses of compression throughout the matrix. It does that laterally and vertically and all directiond between. SMA hasa higher stone content and the stones are what binds together, designed to be irregularly shaped, they mesh together and create a stronger matrix because of their shape. Rigid construction , like the M27, a perfect example in its bare form . The surface is so strong, the way it transfers load is a bit different. Concrete slabs have a very high wear resistance. The surface now on the M27 is as it was when built, not been changed. The slabs are starting to reach the end of their life but its been a long and hard life. Concrete was a favoured method through the 60s, when the housing estates were developed, along with the motorways. They form the basis of a lot of the roads today, called composite roads. A work pic of mine, as usual of a pot-hole these days. A surface of AC but showing thru are telltale lines of the joints which have recently been filled. A concrete bed below. A rigid road base and flexible road course on top. A photo of Havant Rd on Hayling Island. A water leak that occured last year. Surface course with binder , added on top of the original concrete base. Originally a concrete road and then smoothed over , not a thin layer, but binder surface coarse on top. Slabs and block paviours , very popular in scenic areas, such as town centres. Also in modern residential estates, however its the bane of our lives. More traditionally cobbles, like Quay St in Lymington , I don't believe thats changes in several hundred years. So load distribution. When you have rigid pavement , the load is distributred evenly throughout the slab. Unfortunately the slab ends, at that makes a focus point. This is where sub-base is imperative, if it fails , that slab will start tilting. Typically these slabs are about 7m long x2.5m wide and I've seen them rocking. In this rocking there is stress on the reinforcement in the slab and then the concrete is likely to fail. When you see cracks forming , thats due to differential movement in the slab. This cracking can also be due to temperature changes. Flexible road is more adaptive, it allows the peak of pressure to flow through it. Pressure is greatest beneath a wheel , but with multi-wheel there will be different peaks and troughs of pressure off those wheels. Ashphalt deteriorates over time, going brittle with age, brittle when exposed to cold , or too much sunlight. More brittleness means its a lot less adaptive and a lot less able to transfer vehicle pressures , passing over. Micro-cracks start appearing and the stone content starts to be plucked out, then localised defects. This failure transfers to the binder course at the surface. Each council has different categorisations of defects and different priorities. Hampshire's are 40 to 50mm , Soton is up to 70mm so roads in Soton will get a lot worse looking before actioning. Thats all in response to their risk assessments and other safety related stuff. I just maintain them to what I'm allowed to. Another cause of plucking is wetness. If the road is under a tree, it can create a shadow where it stays damp for a longer period of time. If you drive through a wood , and the surface deteriorates its due to the road surface being wet for longer. That moisture is deteriorating the asphalt, then allowing the stones to be plucked out. Spalling is a reflection of a failure at the base of a road. The surface ashphalt is flexible , more flexible in summer , less so in winter due to the temp. But a crumbley surface shows its been overloaded because the foundation has collapsed. That may be the constuctor's fault rather thantraffic's fault, insufficient compaction , or some voids present or water ingress from a leak of a crack somewhere else or a utility company has dug a trench that has washed out the base. You'll get more spalling in older roads. In newer roads you can get more deformation as the result of something called heave. A pic of such an area of damage, still a good running surface , but the affected area is soon to break out into a pothole. The more spalling, the more water allowed in to the roadbase , followed by an exagerated deterioration which will continue until you deal with it. This will need a complete edge reconstruction or haunch repair as we call it. So requiring 40mm of the surface course removed, 60mm of binder course and then further 100mm at least of the roadbase type1 of earlier, could be as deep as 200mm to repair it properly. The reason behind that failure pictured is its seen a considerable amount of HGV traffic on only a residential road, because of a developement down the road. Al lthe lorry loads of muck , brick deliveries etc, all going over it. Developers do pay a fee for developing and some of that money goes to improving the roads, some to repairing such damage as this. A concrete slab failure , a composite road , surfaced over with AC. Spalling again, reflective of the concrete base which has failed. There is 80mm of deflection within the hollows. That is further worsened by some of the material being newer material of previous repairs, that had heaved up creating 120mm of height change. This is due to buses, purely due to them stopping at that point, a bus stop. As they arrive , they break , just normal gentle sedate breaking for you on the bus. But under the bus in the road , large localised repeated pressure , causing this localised failure. Also due to the deteriorated nature of the concrete slab beneath it. You can see the location of the joints in the underlying concrete road , the slab has completely failed. Another bus-stop slab failure, a freshly resurfaced road 2 years prior to this photo, deep intencse black layer with a puddle within it. The pooling water has liquified the base under the slab , every time a bus goes over it a little mud volcano erupts as the road base gets forced out thru the cracks. Reflective cracking - a composite road on which you can see the main slabs but broken out into sub-slabs, observed as reflective cracking. So someone resurfaced the road, keeping the concrete base, it didn't need any work. But it did need work, it looks ok for 10 years and then eventually, through changes in the weight distributin in the slabs and temp. Concrete under the tarmac , cracks at a different rate, causing these fractures. You can see where the slabs are broken and need repairing, but it really needs a new concrete slab beneath it. Concrete slabs are onerous to repair, because of the time required to cure. Once the public have a road they like to keep using it. So we remove the slab and replace it with a flexible construction, which inevitably leads to cracking around its edge , because of the discontinuity of road type. But we can't allow concrete to cure for a month. The only use for concrete these days ,generally, is for cattle grids of the New Forest, where we have no other option than to set in concrete foundation. Vegetation can also be our enemy. Not just tree roots but simple weeds as well. A weed grown thru 100mm of ashphalt, all without sunlight. So its imperative when screening our aggregates , it is completely free of weeds. Some introduced plants such as Japanese knotweed can break up ashphalt and also concrete. We have a log on our GIS system of every piece of knotweed within or adjascent to the highways of Hants. Bamboo is another one. If omeone has bamboo in their garden and they allow it to grow to such an extent it interferes with the integrity of the highway, they are then liable for that damage, and we can recharge them. Trees are slightly different as we like to keep our trees. However sometimes we have to rid them as matter of public safety. Asphalt can deform, a patch about 6 or 7 years old, 14mm stone matrix AC. In some places its started cracking at the edges of the hollow. The centre is depressed 150mm . On investigation we found a large hole under it, of depth 4.5 feet. The public sewer beneath that had broken , the pipe collapsed and the watrer was washing away the road base, 2.5m down. Over time the road lost its foundation , washed down the public sewer and the void opened up. We quickly got Southern Water out to fix the problem. Temporary reinstatement . Often with utility works you haven't got the materials you need to create a good repair. Utility cos have the right to put their equipment in the highway. We don't stop them, we co-ordinate them , having the public interest at heart, limiting the amout of disruption. S oSouthern Electric have made a new connection to a new-build house . They did not have access to the tarmac plant at the time so laid in some cold lay tarmac. Their allowed 6 months before upgrading to permanent reinstatement. This failed i n3 weeks , on Boxing Day and the hole is .2m deep and 1.5m long in a main A-road. We got them to fix it quickly. The original failure was due to the cold and the amount of water , water got into the edge seams , where they cut out and then it froze. Freeze-thaw is an additional method of failure with regards to potholes. Another Xmas callout the A272 in Cheriton , a very large tree came down. We have to keep an eye on trees generally , not just on the highway but trees adjascent too. We have a duty of care, if we notice they are dangerous , we inform the landowner and get them to remediate. If they don't , we can step in using the powers of the Highway Act , to make safe in the public interest, we tehn like to get our money back. Flooding is quite common. It can be as simply due to a can or a bottle in a pipe, obstructing the flow. It can be capacity, too much water in the system. Or simply blocked by leaves. We often find issues with tree roots. We can usually deal with these problems, using a jetter , high pressure and suction water tanker. I think it can use 1500psi pressure hoses, to blast through the pipes and use suction to clear it all out. Roots totally filling the pipes , then you need special tools, root cutters. A different type of jetter that can cut thru roots using a sort of flail , driven by the water pressure. With such a blocked drain, it prevents the system from working and you often see , the surcharging of water thru gullies in hte road, skip a section of blocked pipe and then go down the next set of drains. It is often at someone's property where it gets to the lowest point or pool at the side of the road, in a place where it used to drain, but is full. Road Traffic Collisions. This one, a drunk driver, in Waterlooville took out 2 sets of traffic lights and 2 sections of pedestrian barrier. We have the power to recharge the responsible parties, typically covered by the insurance, failing that the person is liable. A hit and run incident, unrechargable , someone nearly drove themselves off a bridge. Fly-tipping. In this case a pile of fresh horse manure dumped in th e road , near Bursledon. We have the responisibility to keep the roads clear , but in instances of flytipping occur it is the district or borough's responsibility to clean the roads. Often they cannot work on open main roads as its deemed too dangerous. In those cases we work with them by closing the road, allowing them to clear it. In this case myself and 2 contractors spent 45 minuutes shovelling. Planned and routine maintainence. Planned is when we do resurfacing works, surface dressing works, rejuventaion works , also fixing drainage problems. A prime example is Hambledon recently. Serious groundwater flooding a couple of years back, we designed a large-scale scheme , dug up the whole road length , implemented a large drainage scheme . The "loose chippings" signs of surface dressing , a method of waterproofing roads that are nearing the end of their life, but gives them another 5 to 10 years , depending on the traffic levels. You lay out a bitumous emuulsion , you pass over with a chipper, like in hot-rolled ashphalt , distribures evenly a layer of stone chip[pings, across the freshly laid surface. That bitumous emulsion acts as an adhesive and when coupled with a roller. The public usage also presses the chips into the emulsion, as it takes a while to set, hours to days. Sometimes to reduce the amount of loose chippings , a second coat of emulsion is run over those chippings , to adhere better. It is more expensive but it too adds longevity. Micro-ashphalt dressing - a bitumous slurry which contains a lot oof fine stone chippings. Its laid a lot thicker , about 40mm as opposed to a single layer of 4mm stone. Its heavily used in residential areas and is a durable finish. It almost looks like new road. It is difficult engineering for all these surface dressing processes as it requires us to calculate the existing road heights , and new road hweights. Whether the existing drainage systems, kerb-lines etc are suitable for footway levels, are suitable for the new road surface height. When #new roads are constrructed , they are given an amount of adjustment room to allow for future resurfacings. So we don't have to rebuild the network when we go for these types of maintainence. Jet-patching - similar slurry as used in micro-ashphalt can be deployed from a nozzle. It can be manually controlled or on a boom arm , its very quick, trafficable within 5 minutes of being laid. It needs minimal comp[action and is perfect for quick-fixes. Often a jet patching crew will go along a road before a surface dressing contractor comes along. To fill in the defects that would express themselves thru the surface otherwise. Otherwise we have to cut out and patch using the traditional method. Jet patching has been only used for the last 5 years and has become very popular because its very cost effective. As a county we only pay for the volume of stone we use, its very convenient to send a jet-patcher down a road . such pot-hole filling does not mean the road is off our radar , because we know its starting to fail, but at least we knpw the public is safe after the jet-patcher has gone down there. The machinery for road-surface resurfacing. A planer , passing round one of its tungsten teeth. They're mopunted on a drum at all sorts of angles. They break up the road surface, feen onto a conveyor belt , disposed of by the leading lorries. The planer drum is fixed i n position, unadjustable . The tracks move , in height terms , to get fine adjustment , an accuracy of 5mm of planed off height. This is imperative, because of the margins we are allowed in resurfacing levels. The thinest layer we would resurface on a carriageway is 40mm typically. After the planer, its swept. Road sweeper vehicles have very stong suction, they can lift whole manhole covers, out of the road, so they have to switch off , going over them. A paver, this one abroad does 7.5m spread . Typically in the UK we like to lay no more than 3.5m at a time. We have issues regarding the temp of the bitumen and AC we're laying at the extremeties of the paver. The hot ashphalt is tipped into the front hopper, then a series of augers that distribute it thru the machine , onto the back where its levelled off and smooth tamped with a boom. Keeping the width down to 3.5m increases the life of the surface. A thermal image of a recently laid road surface, the highest temp is 150 deg. We struggle with temp as the trucks we use aren't insulated. The material we receive starts at 150 deg, by the time we receive it , just covered by tarpaulin, its down to about 120 deg. By about noon it dropped to about 90 deg and by that point, if still doing repairs i nthe afternoon, you're doomed ot a failed repair. In that situation the material cannot be compacted enough. Thats why you see road crews resurface working early morning and little action in the afternoons. There are hot-boxes that are gas burners on lorries, keep that material hot throughout the day, however ashphalt doe sdeteriorate thru time, it cant be kept hot forever. So we still suffer from material degradation by the end of a day. Recently we've engineered ashphalt with admixtures, clever people at Tarmac etc ,have managed to get the point of laying , to be cooler , nearer 90 deg. Its more expensive because of the additional chemicals , but its more cost-effective because we can keep it warmer, as not loosing its heat so quickly as readily as the higher temp material. It now coming into favour. For large scale paving, the lorries used are insulated. The 20 ton tipper trucks are insulated, they can sit for hours and no problem , usually. This is all a challenge for small crews and small jobs. After laying , its vibro-rolled, after tamped and levelling by the paver. The drums of the road roller have a vibrating mechanism inside , to further compact. For hot AC, it gets the chipping sinto the surface. The drums are constantly wetted to prevent from sticking and sinking in. It also cools the ashphalt a bit, not enough tso affecting the final surface , but enough to prevent them getting stuck. Hedge cutting is often done by the local farmer, having grown the hedge and having the rights to the hedge. Grass cutting is often done be a contractor for the county or district , by agreement. Flail mower is used for both hedges and verges, a drum with chains , several thousand RPM , breaking all in its way. Generally now , just one cut a year in hte countryside . In urban areas its more frequent. Hedge cutting is only done outside bird nesting season , which I think is oct to march. It can be done in htat season if it can be proven there are no birds nesting in the hedge. Gritters. Soton do dry gritting , distributing rock salt on to the highway. Hants is a bit more advanced , we distribute a wet mix of rocksalt and brine. The brine is stored in side tanks of the vehicle and salt in a hopper. If it snows, the ploughs go out. We also have local farmers, on contract, to do snow ploughing, when on the ground, if they are awake and would like to be paid. We licence the use of skips, scaffolding , flowers, banners and structures on the highway. Such as building-site hoardings to a gazebo for a charity function. Streetworks coordination - trying to keep the network flowing, given the demand of all the statutory undertakers have on the network, repairing, installing, maintaining and improving utility networks. We are also bound ot do safety inspections. Inspection of the condition and safety of the highway. Typically a country lane will have a yearly inspection , a residential road in a housing estate also yearly. All counties now are encouraged, by national government and a change in the funding process, to adapt their inspection and asset maintainence and knowledge t be more adaptive. If an area is deemed to be getting more footfall , it should also receive more safety inspection. eg an A road will be inspected 12 times a year at least, but does it need more. Adaptive can mean by the management of the data they hold on the network and the way the network is used. Q&A How large is the organisation of Hampshire Highways? Hundreds of people, in all areas. The customer services side based in Winchester, reactive and routine maintainance tyhat I'm part of , in 4 main depots , Totto, Hook, Bishop's Waltham and Petersfield. There are smaler depots at Andover and Havant. THere are also sme drop-in centres , for all staff, dotted around the country, dependent on their needs. The planned maintainance team also in Winchester. Theree is a legal team devoted to highways law and claims issues. So at least 250 people. Planned maintainence is structured like building projects? Hampshire Highways is a joint venture of the council in partnership with Skanska? , recently won the contract. It was up for renewal in August , other potentials were Balfour Beatty, Amey the previous incumbent holder, and up to 12 year contract, 7 years with 5 year possible extension. The Highways Dept has to loose 19 million out of its budget for the next 2 years. 19 is a considerable proportion , the amount of savings per dept throughout the county are uniform , the same percentage funding cut per dept. I think its about 15% of our bufget. Part of the contract is about innovation and with this modern concept of adaptive asset management, that is required to get the funding from government, better funding if better managed highways, so that is the focus on. More adaptive, more proactive and more preventative to our maintainence. Like using the jet-packers to make the roads safer , and by this patching prevent the deterioration and worsening. Depending on the type of failure, you might be able to surface dress the road, to give even longer life. We're still exploring ways such as this. Do materials, like planings, get re-used? Hants is being innovative, we have a tarmac plant, not quite operational . Its not a proper tarmac plant, its a recycling plant, it takes the road planings and creates whats called a hydraulically bound material out of them. A bit different to the bitumous binders I showed earlier. They have been tested and tried and is about to strart rolling out across the UK in more numbers. An issue is , Hants council has to give ourselves a waste-handling licence to transport the planings , recyle at our new plant , then sell them to other counties for a revenue stream or recycle withion our own schemes. It cant be used in some places, like the surface course of roads is not appropriate, so footways and less trafficked areas. The quality is not as good as a fresh material. S oa matter of using the right thing in the right p[lace. The binder coarse can be made of it, and we will be regularly using it there. The binder course is typically 1/3 the size of the surface course, 60mm binder and 40mm surface coarse. I've seen out on the roads , vehicles with big signs on them saying road surveying. I've not managed to determine whether they are sniffing for gas leaks or penetrating radar for voids detection under the roads? Its neithe rof those , its surface scanning , measuring the deterioration of the surface, not for voids. That then feeds into the asset management software and becomes a check for or against resurfacing . THe only time I've seen a road crew doing a pothole filling job, rake away the loose bits. But when traffic creates a pothole the sides are either vertical or chamfered outwards. But I rxpected them to chisel , to make an undercut around the periphery of the hole , to give some key , or it would just lift straight out. But they didn't and I get the impression they don't do that anywhere? Typically a patch is cut. In America they don't cut, they believe the rough edges give a better adhesion. Everything is coated with a tack coat , a bond coat around the edge , creates a waterproof seal and allows the 2 parts to stick together. Its a lot easier to create a waterproof seal on a fresh cut edge than a rough one. The cut could be canted over, rather than vertical? But then you cant get the compaction . The vertical edges are what keeps the compaction into the patch. Loose that and the edges of the patch will fail. If you've seen anyone just putting stuff into a hole, thats just a temporary repair, not classed as a permanent fix. Sometimes such a repair will last only a couple of weeks? That can depend on how wet the foundation isvor how hot or cold the tarmac is at laying. The railway track out there has notorious problems because of underground streams , running off Portswood high ground and in railway engineering terms they call that a wet-bed, and it all disturbs the ballast with the bouncing of the trains at high speed, is that the same term in your area of operation? Its much the same for us. There is a notorious bit of road at the bottom of Bevois Hill , whee there is a major underground stream and all the ground there is sand. It simply washes out the sand and every now and then there is a huge cavern, sort of half the size of this room emerges, perhaps every 10 years? We have isues on Hayling Island with running sand, similar problems. Same problem with the railtrack at Swaythling, having to put in stones for drainage purposes? What considerations do you have to make with different underlying soils like clay ground ? That is down to the designers behind planned maintainence. In my work i put back what is there, I'm not allowed to improve much at all. If you do see an increase of the pliability of the soil , if clay it would have a certsin California Bearing Ratio or a Hang-Sheer Bear ? ratio where it would be calculated how much strenght the material has . Often,if not strong enough , it will be removed. For instance the new Bordon-Whitehill relief road , a lot was sand which was removed and then built up with suitable stone, to make the sub-base, before laying the road-base. In the old days t get macadamised roads over moorland, they built rafts of wood or heather , float them , and then build the road on top. That is still done to some extent today still. Drive over moorland roads and you find they have an undulating nature, due to the failure of such artificial formations below. So, for a nice smooth road, they put stone in the dips , and raise back to an even surface, just makes the problem worse. You really need to stop and then start again. If 40 ton HGVs were going down Roman roads , how would they have fared compared to modern roads? They'd have disintegrated straight away. The image of Havant town centre, where the weekly market is held. No more than 7.5 ton vehicles coming in , slow speed, once a week. Every month we inspect , and usually 30 or 40 loose paviours every time. Its just not suitable. You often have your modern housing estate , with small raised tsables to slow down traffic , out of concrete blocks or granite sets or cobbles and they will disintegrate unde rthe bin lorry or delivery lorries. A maintainence nightmare, a brilliant idea, fulfills the planning criteria , adding traffic calming , but it just adds ongoing costs ot maintainence. Pired-up double wheels on axles distributes the load, and your slow speed market delivery situation there is no bouncing, compared to women in Stilletto heels and intense local pressure, whats going on there ? The issue is you approach a slab , its fine when your on the middle of the slab as you are spreading across the whole slab. Hit the edge, you focu a tthe edge , the rocking starts . Slabs and blocks are only bedded onto compacted sand, not waterproof either. The continentals seem to be able to do block paviouring a lot better than over here, taking slow heavy traffic ? They probably have thicker blocks. If you have blocks say 150mm depth , they'll bind together a lot better because they won't be able to tilt and rock. 70mm slab or depth of block doesn't have that going for it. The other golden rule, seems to be, don't disturb the subbase unloess you really have to. Long term compaction is far better than short term vibro-rollers and flapper plates? Yes, and utility companies are constantly difgging up / disturbing and that contributes to wear and tear of compaction over time. We will always have maintainence because you can never perfectly put back what you took out. Down the road here in Kent Rd, I don't know what the recurring sewer problem is 5m deep , having to excavate down with shoring and long reach Hi-Macks, do what they have to do, fill in with compaction as much as they can , but 6 months later a great dip in the road? I remember the M27 being built and there was horrendous amounts of water over the clay, so roadlaying in what was basically lakes on clay. How has that transpired in maintainence terms over the years? I'd expected disintegration ? Slabs are stable ecause of their size and distributing their weight over the sub-formation. Everything below the slabs would have bee compacted down beforehand. Its all about compaction f the base, otherwise you #end up wiht rocking slabs. There is an amount of movement within each slab and also an amount of movement from expansion and contraction from heat. Hence the putty between slabs. Different rates of movement and they will show up this differential movement in eventual cracking. There is an innovative surfacing that is quieter . A familiar bit of road I regularly go down , for the same traffic , the road environment is quieter, 100 yards away , than what it was before? It loks ordinary ashphalt to me? Noise from road surface is a combination of the tyres your driving on and how the air excapes . The noise is created by trapped air escaping from under the tyre, as it gets compressed. S o an off-road tyre on a 4x4 is a lot noisier , as more air is trapped and released. If you increase the texture of the road surface, you allow more air to pass out on passage of the tyres. And also a surface-water effect with that? Yes, its hard to balance. So its a sort of microstructure variation , that is making the surgface quieter? Does that wear off with traffick usage ,and disappears over time? Eventually yes, then as the stones get plucked out as the ashfelt gets tired, it gets noisier again. For the new patching materials and water ???, On my pushbike and when its really icey when it becomes icier is it more of a problem , more slippery cycling or driving over? It could be, it depends on the depth of water on the surface. You will find that new ashphalt is more impervious to water than older with its microcracks. So a newly surfaced road will be slippier when wet , due to this imperiousity. Yes be more careful. Some roads are less grippy when re- surfaced than after they've worn in. Hence slippery road signs around , after especially SMA . I call them squidges, conflation of squirm and ridge, but if you have a bus lane , I assumed it was due to summertime softening of the tarmac but it humps up into ridges. A lorry driver once told me that its due to leaks of diesel fuel softens the ashphalt, not just a summer issue.? Called heave. Diesel does deteriorate ashphslt, but those ridges aren't caused by diesel leaks . Its because they are running in the same track , an overloading of the surface, which is not strong enough for the required use. Also the foundation could well be failing and the bitumen is adapting to that. It deforms more in summer and will crack more when its more brittle in winter. One of your biggest enemies is frost, is the worst form the amount of freezing and melting cycles over a few days, the depth of the frost or the duration of the frost? Its all bad. We put salt on the roads, thats bad for ashphalt in the long term. How often do you manage to get money back off those that have casued damage. ? Our previous contracter was supposed to , but didn't and our new contractor has not started yet, but they will. We take a police reference number and the recharge team gets engaged on blame,fault and billing. Billing for our time, assesments and repairs. Street lamp damage is separate, processed by the street lighting team. What about not necessarily criminal behavious but vehicles goiung where they shouldn't and causing damage? Leigh Park housing estate, Havant, designed without private cars in mind, just public transport catered for. We can't go after everyone who parks their car on the grass. Its cheaper for us to repair the damaged grass verge with some stone to harden it. Discourage it ,yes, by strategic siting of posts. In previous times there was money to increase parking in Leigh Park, but no money now, there are plans for mor ebut no money for them. We've seen much increased applicatins for parking spaces in increasingly more inopportune positions. Its costing the home-owners thousands to do so, but it does allow them to park up. However its a source of many neighbour disputes, because one person at the farthest point will pay for it all , the next door one can then get in cheaper and the original applicant gets miffed. It causes a lot of issues, trust me. Why are the roads in London much smoother than the ones in Soton? Hampshire's criteria for a defect starts at 40mm , we will act on at that point. Soton's criteria for a defect in the road is 70mm and not bothered about repairing anything less. Generally it depends on the local authority as to their road maintainence standards. Involving risk-assessing, and proving, there is no definition of a pothole in terms of size. The roads in London have more money spent on them than county roads. Smaller network, more concentrated , has more traffic but also more money spent on it per road km or square km than ever the roads around here. Is there diferent standards for the road near junctions? No. A crossing point can be upheld to the standards of a footway potentially. A footway defect starts at about 25mm . The get-out clause is theyy are all visually assessed, no tape measure involved. Its what I think by looking at it. By footway do you mean pavement? A pavement is an entire metalled surface , a footway is where you walk up to the curb or a small verge separating . Carriageway is where the vehicles drive and a footpath is remote from a carriageway. I think Soton has 40mm for footway and 70mm for carriageway defect point. Are areas of high-rateable value houses have better quality road surfaces and maintainence , than low-ratebale value areas? There might be some truth, when we start getting political. Who shouts the most at their councillor , thats where some of this maintainence malarky breaks down as some people kick u pa lot of stink about nothing which you then have to spend money on and then you get something a lot worse that no one cares about and no money to spend on it by then anyway. There is a political aspect to some of this and I have to kick myself when money is spent on stuff that is irrelevant, just because someone high-up says so and I cant say no. Each area or district or burrough has its own pot and that is split between the 4 depots of Hants council. Some of them spend all the budget, some don't, some share it some won't share. New forest road construction is inherently poor as so many of them are just laid over gravel and nothing can be done about that because of National Park status , which means maintainance has to be as-is and no improvements allowed. In WW2 connecting the airfields , concrete roads were built around Beulieu and hte roads to Fawley Refinery but not otherwise. I've never seen a dilapidated cattle grid, they must need some work keeping good? I think there is 160 in the New Forest. THey've been recently re-designed to be completely modular. One of our engineers designed them from scratch , complete with hedgehog ramps. So pre-fabricated sections and just bolt together. Previously they wrre bespoke or welded , using girders and all sorts. Now they're galvanised to last a lot longer and replaceable in sections. I've never seen any bent "scaffold tube" , they don't seem to be thicker gauge than scaffolding over quite an unsupported span, with no knowledge of what weights will be going over them? 10 foot span and loaded HGVs are fine, for the modern grids anyway. ??? siding out? Its not carried out regularly so when we get to it , it requires further maintainence . In my area its mainly verges going over fotways. The footways will have concrete edgings , that gets overrun be the grass verge, driven over a few times and the ashphalt abutting the concrete wil lhave deteriorated by being kept wet under the spread verge. We maintain our footways at a minimum of 1.2m , typically they'rw built at 1.7m in width and the absolute minimum is 1m . However in historic areas , where trees grow and grow , in some places i have footway that is only 0.7m, which is difficult for wheelchair passage. In such situations you have to assess whether the tree is suitable to be there any more. A recent case a tree was blocking a footpath but the public can get off the footway , due to an old vehicle access, not putting themselves at risk, so the tree stayed. Siding-out? Pushing the verge back , or in country lanes it can be growth over the carriageway over the ground or residential area footways. Where verges or hedges can spread out. Why cut the grass? Visibility quite ofetn. We cut the grass back 1m from the road edge, to prevent it growing over the edge of the road, eventually leading to an obstruction. At junctions we cut back further and mor eoften , to maintain the visibility. Cutting the grass less often would eventually make our jibs harder, verges will become more vegative with brambles etc. Road sweeping is down to the districts and butrroughs, differnet in unitary authoriies like Soton, where they are responsible for everything. They have a road cleaning schedule. There are times when we have to clean the roads specially for safe passage. Recently in Stubbington we had a fodder beat harvest , harvested then carried by tractor and trailer to a depot and during all that, a considerable amount of clay on the road, the road lost its texture depth , so almost like driving on ice. It was dry and cold , but not iced , although acted like ice. We had to close that road as it was so unsafe with the compaction of the soil into the road surface. Cutting back vegetaion for visibility purposes but sometinmes coming up to roundabouts , there ar eobvious visibility intrusions to stop the visibility? To slow people down. You have to slow down to see, to stop people tearing onto the roundabout . One roundabout will have vegetaion cut back and then the next roundabout will have ant-visibility barriers in place? Visibility to a sufficent minimum which those baffles do. There are planning criteria for them . Surface dressing where they put emulsion down and then stones , then we have to drive it in, then all the stones scratch the cars and spread everywhere, then they sweep them up and the reason for that pallaver is its cheap and gives a rugged 5 to 10 years more? Soemetimes 15 years, then do the same thing again. thats how long the surface will last. The surface under isn't being run on , so is protected by the newly placed surface. So we're maintaining what is already there , in its state then, into the near future. There can be problems with that. For instance when it was particularly hot in the New Forest, they surface dressed the A337 to Lymington and it just melted. The bitumen emulsion flowed down the road, a river of tar. Disastrous and they had to do the whole thing again, and claims for tar damage to the cars. Incidently tar not used these days as its carcinogenous. Did steam-rollers come in before tarmac or after? The roller has always been around, its just the amount of compaction that could be generated has increased. Originally it was horse drawn rollers . If you wanted a drive done to your property , for a car , what surface would you recommend? and what underneath? You have to ignore all I've said before, because planning states you must have a porous surface. They do do porous ashphalt , but because it is porous it is self-defeating, bacauase water is bad for the foundations. Its not so bad for the useage in that situation, but get removal men turn up and too much. Porous block paving is probably the safes tbet. You use a specific kind of sand between the blocks, no cement, there. If you have clay below then it will all wash away. There are suitable products ut there. Gravel and plastic tiles that are porous , above clay is one such. But the clay would still bleed through a bit. Porous requirement is to prevent surface run-off and flash flooding. So a linear drain at the end of the drive, it never fgoes anywhere , but it should. Because you are supposed to deal with the water that lands on your property, within your property. Often you pay for that in your water bill. Your rainwater gutters flow either a soak away typically 3m from your house . Incidently need to be dug up every 25 years and be re-stoned, disposing of the previous. Or go into surface water sewer , not into the highway drainage. As we should not have to deal with "your" water, unless its naturally flowing off a hill , say a farmer's field that is above you. With your mangled-up verges in Eastleigh , there is that thickish black plastic mesh reinforcement mat you just lay over the grass , and it grows thru. You don't use anything like that to reinforce. ? The only time we use that sort of material is where there is a vehicle access or a footway near a tree, so not allowed to do any digging near by. Its not the sort of thing we can maintain in a highway sense, as not to any specification . The grass simply grows thru , so environmentally it looks good and does the job? Yes W approx 70

12 February 2018, the intended speaker did not turn up as in hospital with a life changing condition. From the audience we had 3 volunteers with a 20 minute talk each. Roger Anderton, speaker Roger Boscovich was a priest in the 18C . There was the Copernicus revolution , then Galileo, then they had problems with theh inquisition, because the church did not agree with what he was saying about the Earth going around the sun. Along with that there was a problem with atomic theory. Atomic theory was seen as being aetheist. Then Newton took up the ideas in England, where there was a bit more freedom, regarding physics, also the Royal Society, for which the king had given them pardon, to talk about things that were otherwise heresy. The catholic church had to reconsider its position on the new physics. The leading light in the catholic church was Fr Boskovitch and he managed to get the ban on Copernicus teaching overturned sufficiently to also teach Newtonian physics in catholic countries. Part of that was the idea of atoms. Newton had his gravity theory and insight into light but he did not have a complete theory of atomic physics. This omission was filled by Fr B. He wrote a book on it in 1758 callled the Theory of Natural Phylosophy and was the basis for modern atomic physics. You look at the others working on atomic physics, Rutherford, Niels Bohr, Heisenberg and others, they had a starting point of B's theory. Even the Manhattan project, the theory they were coming from was Bs theory, developing it on further. Einstein came along and from his influence, after WW2 , B's theory was not taught. To make room for Quantum Theory and Relativity Theory , to physics students, they cut out teacing about B and any physics from the 18C. Bohr and his contempories knew of B , but since WW2 he was totally cut out from teaching. Then you look at people who were working on Unified Field Theory, B was there before. How the particles interact with the fields in B theory, that was also removed from teaching syllabuses. Bs theory of UFT is now consigned to historical studies of physics. Q: What was in B's theory? Particles . Atoms concept go back to the ancient Greeks, with Democrus? and Epicurus et al. Then the Christian movement happened, and up to the middle ages, that concept was considered heresy. It came to the fore again with Copernicus and the catholic church had to reconsider its position on atoms. How did Dalton get involved with this? Dalton was working from Bs theory. B had the theory of particles and Dalton was talking about a chemical element, the atom of a chemical element. For say silver you could cut it down to just the atom, cut the atom further then things like the nucleus and electrons emerge. So well beyond the early Greek theory, that it was something simply uncuttable. Dalton's atom was a chemical atom and was cuttable. So sub-atomic particles. Dalton believed atoms were fixed? Daltons atoms were not the ultimate atoms, you could cut them down further. Later with Richard Feynman he was dealing with things called quarks, he treatred quarks as the smallest particle. He referred back to Bs theory in how to handle that. Another person knowledgable of B was John Wheeler, setting up his school for relativity after WW2, part of his teaching was from B theory. When he was trying to get a UFT, he called it Quantum GeoMetroDynamics. But that had its roots back in the 18C. Einstein looking at UFT failed to unite quantum mechanics and general relativity. The 18C UFT was worked on later, there were mistakes though. In Bs early days was he a physicist who went over to religion not letting the church hierarchy know of his physics background ? They were'nt called scientists back then , chemistry or alchemy was the major science, then phsics was just a bit of chemistry. He wasa natural philosopher in there terms. The priesthood he was with was called theSociety of jesus, the jesuits. They swore allegance to the pope, and that gave them exemption to things that were considered heresy. So a ban on Galileo's book , but that really only applied to the general populace. There were special people who were allowed to look into , to reconsider it. And B was the main man for doing that. Even today there is a well respected astronomical observatory attached to the Vatican? , so that has carried on thru the centuries? There is a link between B and astronomy. I go a lot to Serbia , they know about B. So a conspiracy to supress B? How do you define conspiracy. If you look at say the Manhattan Project. General Groves was in charge of it and part of the structure there was to delete things from physics which were considered to come under national security. Was that a conspiracy, i'd posit. You're saying that anyone like Dalton couldn't mention B by name? He does mention B in his writings. You go back to the early 20C , the scientists then knew of B. So Mendelev of his series, did not mention B? He was Russian, the main man in Russia of that time was Lamskovus? he was working from B theory. Dalton based his work on the way he observed chemicals combined together, in fixed proportions. Did he get that idea from B? The theory of particles goes back to B and 1758. Why did B have a theory of particles? He had to reconsider it , because of the Copernican revolution, the Greek ideas had to be reconsidered. He had to come up with a theory that the catholic church would be happy with, Fr B did this. It allowed Newtonian physics to be taught in catholic countries. In England, what we know as Newtonian physics is from Newton, but go to catholic countries , at that time, they knew it as B theory. Did B work this out for himself or was he translating Newton? He was looking at Newton's work and extending it further. Newton had objects attracted by gravity , such as the Earth and moon, but no talk of repulsive forces, only attractive force. For a more complete theory you have to consider repulsion as well. Did B talk about fields? He called them spheres of influence. You had an object and around it was a sphere of influence, that would influence that object. When Faraday worked on this , he called it fields. For people working on UFT, they had David Bohem with an idea of pilot waves, that they worked on. Bohem run into a problem as part of MacCarthy witch-hunts , he was accused of being a communist , so that side-lined him. UFT was to combine gravity and electromagnetism? That was the intention. The forces were acting as per B was saying. An attractive force and a repulsive forvce and it has to obey curves. So not like action at a distance like gravity? One way of thinking of action at a distance is as fields, the gravitational field. Gravitational Field , considered by Einstrein as space-time curvature, where space is given the attributes of a field. Einstein's work on UFT went back to the 18C. David Bohem had a student called Avije? who does conferences on this subject. I'm trying to get people , when they write any physics theory , in this area , to consider the work of B. THere are people like Prof Rowlands of Liverpool who I believe has written a book on it, connecting in to hs own writings. A chemist Prof Munroe in the states is incorporating it into his theories as well. Roger Anderson had translated the works of B, into a book, that he passed around the audience. Ron Melville :Positive Money i started asking the question 3 years ago - where does money come from? People say it comes from the bank or the post office. When you go to get your mortgage , you go to a mortgage company, usully related to ta bank. They say you have enough collateral, we'll give you a mortgage. They go to a computer, type in the number and suddenly that money has been created that did not exist before. It seems a remarkable fact but basically they just print money. Economista say we can't simply create money or we'll create inflation . But we've ended up with bamnks that create money when we take out a mortgage. So what happens if all the mortgages are paid off, well ther'd be no money. You start to realise that money is based on debt, apart from the coins in your pocket. It is estimated that the hard currency in circulation is about 3%, 97% is numbers in a bank. THe problem with debt-based money is that it attracts interest. If you have to feed the interest system , you are tsaking money out of the system all the time. The system becomes leaky and apart from the balance of payments problem , another way to have money leaking out of an economy, you have a leaky system. What happens to the interest is a an interesting question and I'm sure most of it doesn't get circulated back into the economy. The only way to compensate for that is to create more debt, to keep the system stable. A lot of politicians don't understand this , they think austerity is the answer, taking money out of the system has the opposite effect. So we have a system we have to keep feeding by creating debt, to compensate for the interest and the money coming out of the system. So politicians say we must have growth to compensate. We live on a finite planet, we can't continue to have growth. There is a quote that only a lunatic and an economist would say that we mus thave growth. A bunch of other people going around saying this system cannot work, it will end in collapse. They said, we are doing this the wrong way round. Instead of basing money on a minus sign , lets create money on the plus side, so we call it positive money. There is a +money group in Soton and across the UK. They say , if governments can create money by pinching it , which then does not attract interest, you can strart taking control of the economy. Not having to money in the form of interest out of the system you can start towads a more sustainable society. Some go further saying go for sustainability , not continual growth. We all fear the end result of the conventional structure is collapse and global warmoing. So +m people say we should start creating money , by printing it through an autonomous organistaion that controls the money supply , they print it to be various things in society. When it comes back thru taxation, you just delete it and it no longer exists. That is the basic principle of +m, a sustainable rather than continual growth society. This way we hope you can have a better future. When I hear governments saying debt is getting too big. The last govt manages to double govt debt to virtually 2 trillion . I don't mind if it collapses because we can go to the alternative of a +m system. But the EU agreed that we should go to more debt. For more info on this , put into Google, where does all the money come from AND you-tube an icon comes up with 2 dollars on it , a 40 minute video, it tells you much more about how this system works. I've had to watch it 3 times to get the most salient features. Q: So debt no longer exists? It all depends on how the money is created. Q: So , I can't afford to buy a hous e. You can go to a bank , if they have money already, you can then borrow it. We're not really chnging the banking system that much. They're losing the abiity to print money. Instead of banks printing money , a central organisation does it. Q: Wasn't that what the original building societies were. People put money into them as savers. Yes but its changed over the last 20 years or so. It was actually Gordon Brown who changed it. The Fractional? Reserve System was changed . Q: Could you explain how Quantitive Easing comes into this because the govt produced loads of money to offset the financial crisis in 2008. I know a little about this. When the govt wanted to borrow money it issued a bond that people buy. With QE they just bought the bonds back. They made offers to people to buy back bonds. Where did the govt get the money from, they printed it. The person who invented QE was someone at Soton Uni, apparently. I understand that the original concept of QE was you shouldn't give it to the banks , you should give it to people , to pay off their mortgages . Far more sensible, that way. The first people to try it, were the Japanese, and they switched the system to pay yhe banks, for buying the bonds back. Q: So where has the money gone? I wish I knew . It was said at one time that China had so mush foreign capital th=at they could buy yhr entire real estate in the USA, whether true today , I don't know. Q: Do you know anything about the Islamic banking system, where they don't charge interest. ? They don't believe in usury , bu tthe details i don't know. The have a structure where there is a payment upfront, which is an equivalent to interest as a get-around. So effectively much the same. There is an organistaion called Positive Money, do you know who they are and who funds it. Its out there on www. There was a chap v=called Ben Dyson , an economist , one of the promoters of this. Q: I think they have a point. It is plain simply wt=rong that banks just create money via computers. Then speculators gamble it away, and then financial cre=ises. If I did that, I could become a loan-shark and become a billionaire in minutes. So who is this organisation and why are they promoting it, including their funding, thats what interests me. Who funds it, I don;'t know. the reason behind it , is towards a sustainable society. In my opinion the result of continual growth is global warming and who does that benefit. Q: I assume you're not an advocate of bit coins. I don't know enough about that topic . How is the money based, is the interesting question . Not money at all . Even wider , what is money anyway. Q: The one advantage that crypto-currencies have , over regular currency is coded into the design, there can only be a certain number of them. At the moment banks print money whenever they feel like it, but with something like bitcoin , its fixed. Its value depends on people follwing some rules. Also all transactions are recorded and available . I don't think we'll ever get a sustainable society on the present course, and thats the key to it. So many politicians out there just don't understand this. Q: Third wold countries that want to industrialise and want similar lifestyles as us, cars and excessive energy use. This is the model we've shown them , what do you think the consequences will be. It started going wrong with the FRB system. THat basically says, if you have 100 GBP, you can lend 1000. Q: Before that , there was printing money without anything much behind it. Any correction was via devaluation. In my 60 years government s have been printing money without gold or something behind it. They promised to pay the bearer on demand, but they could easily devalue whatever they had to pay. As my dad said, buy a house and counter inflation. Q: Can you see avarice disappear with +m.? You have to understand the hierarchy of need for this. Basically the human being wants to survive. He needs food , shelter and 5 other parameters, that Mazilo? said. Once those parametrs are acquired you can then head towards self-actualisation - the state of being where you are emotionally stable, you have no anger, no depression, or anxiety etc. Jung called this individualation. Create the demand and people who've had rotten lives , are compelled to compensate for things that have gone wrong in your life. You're dealing with insecure human beings, who feels he has to grab everything available. Another bee in my bonnet. If w echange the education system to help people be more self-actualise? and there are ways to do that, then everyone would be great individually, a utopian world. I did go to Summerhill School as a pupil , so obviously I'll have differing views to other people. Someone who steps outside the box a bit. Q: In Summerhill you could have individualism , people encouraged to be theirselves, to be creative and at the same time , trying to have a community. So 2 apparently opposing forces, without one dominating the other. I think you have had to grow up in that environment to understand it, how it works. I feel privileged to have gone there. Q: Is Summehil where teaching is based on heuristic principles. ?, learning by doing. No not at all, Summerhill says here are classes, they are standard classes . Go to them is fine, but if you don't want to go them , go and build a tree-hut or go to the woodwork shop and bukd something, its your free choice. But what you shall not do , Summerhill very strong on this, you shall not interfere with other people. Interfere with other peple and they have the right to bring that to the attention of the community. Q: Did people work together on combined projects , whether cleaning the kitchens . No one hierarchy saying, I'm above that, everyone is equal. Even the teachers have to be involved. Absolutely, yes. Democratic decisions always. A community based on democratic decisions . Where is the school? Near Aldburgh , a little town called Laston? , still runs today. I phoned up the headmistress last year, because we were going to that area for a funeral , and she recognised my voice from 40 years ago. She showed me around the school and what was going on. Q: People come in all sorts of types and some people are just simply greedy. We need to push people to being towards emotional stability. To do tht bring up children appropriately so they ar e more mentally stable than otherwise. People are raised through rottrn times. The current national curriculum is probably one of the best tools for keeping therapists in business that could hav e been invented. B35

Venue suddenly closed, cancelled March talk, moved to April

Tuesday 17 April 2018, Prof Ivan Haigh, NOC Southampton : Sea level rise and coastal flooding: past, present and future. 32 people, 1.5 hours A graph of time from seconds to millions of years and on the other axis, space from a mm to 40,000km the whole earth. Over all these time and space scales, se-levels vary. At one extreme turbulence and ripples , the microscopic ripples you see if you blow over a cup. A bit higher up waves and swell and seiching, after someone in Switserland who noticed that when wind blew over a lake , if the wind stopped, the lake would oscillate for several days. A seiche sometimes occurs in some harbours, the gentle seaiche oscillation. Then tsunamis , they are quite short lived at a coastline. May spend days travelling in the oceans and affect large sections of coastline. Beyond that is storm surges, the movement of the sea caused by weather. We tend to get 2 catagories of storm surge, tropical storms which are huricanes , again affecting long lenghts of coast but tend to last about 12 hours at a coastline. Then tides, 2 bands of energy, semi-diurnal tides which we have in the UK, 2 tides a day. We also get diurnal tides , in western Australia for example and the Gulf of Mexico, 1 tide a day. We get extra-tropical storms the sort of system that affects the North Sea, tending to last about 2 days. We have seasonal effects like El Nino oscillation , wind can blow on-shore for 6 months or blow off-shore for 6 months , that can raise the level of seas. In the Uk sealevels change by about 10cm between winter and summer, cooler and warmer water. Then we have climate change effects , then beyond that glacial cycles and sea levels change by hundreds of metres. Q: Through the Channel on the French side the sea level can be highe rthan the English side at certain times. Most of that is due to tides it comes in , Coriolas force pulls it to the right , but also strong wind induces that. Q: I was thinking currents. Currents tend to be seasonal, strong currents for part of the year . A lot going on and a lot more . Of all those, 3 fundamental things that change. I have 3 beakers with some water in. There are just 3 ways you can change the level in the beaker. Add liquid from 1 cup to another, add or subtract. Displace it , by squeezing the cup, liqid is incompressable, the same volume, change the shape of the container. Move the water by blowing wind over the surface , to one side of the basin, change the shape of the basin, or you could put something else into the basin, but fundamentally you are moving the water. Change the temperature , put it in a freezer or a heat surce under the cup. Or we could change the salt content. So what are waves doing in regard to these 3 fundamental proceses. Waves move , tsunamis move, tides move, climate change is doing all 3 . The world is heating up , oceans expanding, ice is melting land-based ice is melting, also climate change can alter wind patterns, which might lower SL in some areas and increase it at others. Q: Where would you put air pressure? Water is incompressible , so what air pressure is doing , can suck water in from other areas or pushing it outwards. Air pressure i sa key change , I'd put it under the move box. I will focus on the longer term changes, not tides or waves. So mainly the slow century scale changes in SL. SL had been relatively flat for about 2000 years , averaging out al these processes taking the maen . Over the last 150 years it has risen about 20cm. The key questions over SL rise. Cost of coastal infrastructure damage from flooding or inundation. Reduction of the landmass, coastal wetlands Environmental impact to the wetlands Populations would have to move. Could change weather patterns Low level lakes will become saline. As SL rises you need less severe storms to give the same previous SL rise. So more inundation, and storm damage to infrastructure. An estuary in W Australia, with an unusual shape. The area that would be inundated in a 1 in 1000 year flood. But if we raise SL by 1m a significanly larger amount of land would be inundated by the same event. Its difficult to give an example as SL have risen by only about 0.2m. Sharp's Island in Chesapeake Bay, or rather was. In 18C it housed about 100 people, a farm a, a school , a few hotels. A combination of SL rise and land sinking, in 1950 just a room sized patch of land left and even that is now under water . Wetland loss. Wetlands important for a great rnge of reasons , regulating diseases, biodiversity. In Maryland USA , the natural wetland creeks , with SLR just gets lost. Those areas absorb CO2 , they do lots of things. With SLR comes coastal erosion, The Holderness coast eroded by about 2km , SLR speeds up that rate. A number of houses in that area people are still paying off mortgages on houses that have disappeared into the sea. Saltwater intrusion more important in other countries than the UK. Like the Maldives, low lying atol, a freshwater lens and with rising SL seawater will get into that lens. Peole often talk of SLR directly affecting small islands but while still above the sea , communities cant live there because of the loss of fresh water. Raising water tables, a lot in the States. Fresh water supply underlying but SL rise can push that whole supply upward. Some towns are now getting flooding in basements because SL rise is pushing up that water table. The 5 main key changes. The historiacal context. We cant directly measure SL in thr longer term. Over several hundred thousand years or less. We can use proxies for indirect measurement. We can use saltmarshes , use archaeology a number of sites under water that wern't. From that we can estimate how much SL has risen. We can use spieleotherms, stalagtites . Coral reefs which tend to follow where SL is. We can use geology using sediment cores like ice-cores. With saltmarshes , they tend to have different layers and species of plants at different depths according to whether regularly covered by tide or not. As SL rise, the saltmarshes move backwards. As long as SLs have risen steadily , you can take a core and count the phoram microscopic creatures. Near the sea there are certain types single cell species, and towards the land are different species. This can tell you back about 1000 years, a prof in York does a lot of work on this. A number of areas from archaeology. One example is Roman fish dams, near the sea, almost like aquaculture raising fish in them. These dams are now under water , so we can get a reasonable estimate of SL about 2000 years ago in the Med. Sometimes marks. James Ross Clark went to Tasmania about 150 years ago , he carved a mark on a rock near Hobart that he estimated the MSL at that time was. A friend of mine, John Hunter spent about 3 years doing measurements there and get a good estimate for there over 150 years. Spieleotherms - stalgmites on the ground only form if there is air , if the cave goes underwater, they cannot form. In Bermuda many such caves and a group in Oxford has permission to take some. They form a tree-ring like structure . We can split open the stalgmites and date the tree-rings and see when that stalagmite stopped growing. So SL was at that level about that time , again as an estimate. For corals , different species at different depths under water, mostly less than 50m of sea surface. As SL rise ,the corals migrate as they need light or they die out. Again drilling into corals we can estimate SLR from these dead corals , now very much below current SL. 100,000 to millions of years ago, beach lines at different levels. Sediment cores, especially from the Red Sea . None are very accurate but taken together gives a good idea of SLR over tens of thousands of years. So putting climate change into context. SLs have varied by up to 120metres over the last 500,000 years. That very much relates to the ice-ages. When the world was much covered by ice 25,000 ya , SL was about 100m lower than today. Certainly 2 occassions between 5 main ice-ages SLs were higher than they are today under different climate change conditions. The general theory is this relates to Milankovitch cycles , small wobbles in the Earth's rotation , planets coming in and out of phase causing ice-ages and out of ice-ages. In ice-ages water is stored as ice and SL drops, then inter-glacial stsage SLs rise. So SLs have moved at least 130m . Zoom into the last ice-age and info from corals and 24000ya SL were a lot lower than today. SL gradually rose and then stabilised for the last 7000 years. Particularly in hte last 2000 years SLs were virtually unchanged. Fortunately that coincided with a massive growth in human population. I don't think human population could have increased so much with the previous amount of SL rise. A stable SL allowed us to build coastal communities. In recent times that has started to rise. Without climate change we'd have expected SL to have continued this long stable period and eventually go into another ice-age and drop away. What the UK looked like 20,000ya everything down to about Birmingham was covered in ice . Thr North Sea was land and as SL rose , at about 15000ya , the Irish Sea formed . About 12,000ya water came into the English Channel but we were still connected to France. Then the first Brexit , when England formed about 9000ya. Coming toward the present the North Sea enlarged, but 10,000ya no North sea . In modern times we have instrumentation , tide gauges and satellites to monitor. With the paleo stuff there is a lot of uncertainty, but now much more confidence, measuring SL to within mm now. Around the end of the 19C SLs started to rise. Plots of the 3 longest run tide gauges i nthe world, Brest almost continuous 200 years except around wars, San Fransisco for over 100 years and one in Poland on the Baltic . That rise cannot be explained by natural ice-age cycles , something clearly is happening. Its not a smooth rise SLs go up and down, a lot of noise , the underlying signal is a rise. I get fed up wiht people taking 10 years of data , you canshow things are falling. Take a long enough period, the noise goes , and you can see the rise. Q: You ran quickly over not attributing that recent rise to a coming ice-age, why? If you take similar conditions in the past, particularly when SLs were higher than today. We should have that flat period continuing. Certainly the last inter-glacial we had similar sort of conditions and things remained stable, so some othe rprocess is involved, I'll return ot this later, the individual budget. Tide gauges back 100 years or so and satellites over the last 30 years for a true global picture. Over the 20C a definite SLR about 1.7mm per year but that rate has now doubled in the last 20 to 30 years. SLs are not rising everywhere, very spatially non-uniform. A map from satellites, the mean is 3mm per year over the whole globe. Some areas where its rising 10mm/yr so 3 times the mean. There are also regions where SLs have slightly fallen. You cannot rely on single sites . Taking Southampton , the long mean sea record at Soton that I digitised some years ago. So at Soton rising about 1.5mm per year over the last 70 years but take only the last 20 years then its about 3mm per yr. So quite close to the global average. Most of the UK is the same as the global average. The important point is that that rate is starting to accelerate. The 3 main components contributing. Land based ice, particularly from glaciers . The thermal expansion of water and the melting of ice-sheets. Arctic ice is not so important bu t the ice on Greenland and Antarctica are really important. We can estimate the individual components adding up and giving this SLR. In the last 50 or so years, thermal expansion accounts for 38% of that rise, the largest part ,40% has been from glaciers melting, Greenland only very small and Antarctic smaller contribution. Of the recent accelerated rise then 58% is due to thermal expansion. Less from glaciers because many of them have melted away. Greenland recent compoment has increase slightly. There is a lot of uncertaintly with Greenland and Antarctic. Various pics of a glacier 1885 a whole valley covered by a glacier, 1907, 1930 ,1950, 1970 to what we see today, nearly gone made its way into the sea. Just one glacier ,one of tens of thousands of glaciers. Greenland ice-cover pics 1992 ,2002, 2007 the affected areas dramatically changed. Antarctic has not changed that much. So to the future. The IPCC thousands of the world scientists every 7 years weigh up the evidence. They predict over the next 100 years SLR would be between 28cm and 1 metre, thats the likely range. The UK government have recently been working on this and I was helping with the Environment Agency. In 2009 they said it could between 11cm and 75 cm , a lot of uncertainty with it. Much of the uncertainty is down to what emissions will be in the next decades. There is a high end scenario of as much as 2metres although unlikely. Realistically without a major collapse of Antarctic ice , we're looking at about 1metre of SLR. The Paris Agreement was signed by about 165 countries. They promised they will hold the increase in global average temperature to well below 2 degrees, from pre-industrial level and persue efforts to limit it to 1.5 degrees. Recognising that this seriously reduces climate impacts. What is often omitted , limiting to 2 degrees there will be lots of benefits. Temperatures stabilised but one of the problems with SLR is that we are long term committed to SLR. Even if we cut C emissions now SLR will still carry on for 200 to 3 thousand years because there is a lot of inertia in the system. At the moment we've only heated the water surface, it takes hundreds of years for that heat to transfer down. Its the same with ice, start melting ice, it continues melting, it won't just stop. We will SLR even if we fulfill the Paris Agreement. To predict SLR into the future is computationally expensive using numerical models of the whole world, called GCM Global climate Models. They have to run on super-computers ,only 15 to 20 of these models are run around the world. Most have only run to 2100 for SLR predictions. We've developed a very simple model that will run on your smart phone. Type in CO2 modeller and download it onto your smart phone ( ) . We represent the whole Earth as a series of boxes. An atmosphere box , a vegetation box , soil and its interactions and 5 boxes that represent the oceans, right down to the 3mile deep ocean and the transfer of heat. All these boxes are the model reduced to the simplest form. We've run this model and tried to get it to adjust to certain temps . As its a simplified model, we can run it for hundreds of years , to see how the climate would respond. Beyond 2030 we cannot be sure, but we try to limit to 1.5 deg C . The high emissions scenario will increase temp by about 10 deg C, catastrophic. We've run the model with the out to year 2300 for 1.5, 2.5 , 3 , 4 and 10 deg C . I think we've missed the window for 1.5, not achievable . What is interesting for SL projection is even if we cut our emissions and stabilised to 1.5 deg , SL would continue rising for hundreds of years. With 1.5 deg, SLR would reach about +1m, bu tthe really scary thing is if we continue on our current track, without Paris Agreement, we will get at least 4.5m of SLR. We need to think long term . By 2100 it would not make much difference , with or without Paris Agreement, it only saves about 20cm of SLR, but if we act now we can save at least 3.5m . It is so important we make the PA work, not so much for us but our great great grandchildren. I just produced this yeasterday, a climate spiral animation, 0, 1, 2m SL, with and without the PA. This needs to be on a government level and on a personal level, each of us trying to do our own little part. If all the world's ice melted , about 80 metres of SLR in that. THe Uk would look very differnt , Southampton and Norwich would be gone. This can't happen ,certainly in the next 100 years, not physically possible to melt that fast. What can we do about SLR . The UK has developed shoreline management planning, dividing th e coast into stretches and determining the options. Some difficult choices as its very expensive to defend the coast. So a cost/benefit economic analysis if only defending a few houses. No active intervention on some coastlines , whether a pre-existing coastal defense there or not , nothing more will be done. A colleague in Germany did such a cost/benefit analysis and he reckons only about 8% of the world's coastline would be defended, the coastlines with majoe cities. Q: Thars fair enough if you compensate the people who will loose out but we're not doing that. I was at a meeting yeaterday in London yesterday where we discussed thuis very topic. At the moment the govt will not compensate individuals. We've just seen on TV in Norfolk of people losing their homes to the sea and they're still paying the mortgages. So making that decision , it must be tempered with something else. I would not like to make that decision. Q: We (representing New Forest National Park) are trying to work with DEFRA. We have to compensate the few people it will affect though. Similarly farmers need to be compensated, for lost farmland but we're not dong so, it seems very unfair. I don't like talking about this aspect. Unfortunately the sad reality is we don't have the money to defend the coast ecverywhere. I'd love to live in a house on the beach. Q: You will soon The government probably does not have the money to compensate everyone. Q: Its a matter of choices , they can spend money here or there, choosing not to defend some places, may mean putting resources elsewhere. The govt will have to make really tough decisions that will affect lives and I agree people should be compensated. Other stretches of coast we'll hold the line, definitely holding London. So the likes of the Thames Barrier, millions of pounds in flood defences. Other parts of coastline will have to be managed retreat. I'm working on a site in the Bristol Chanel, it tends to be farmland. About 40 such sites around the UK. The R Paret, they were spending millions of pounds on defending what was just farmland, no economic sense ot do so. They compensated the farmer , buying up the land and let the land flood. It would have been natural saltmarsh anyway. They put in a breach and designed a creek system to get the water going. When a storm surge happens , rather than water going up and flooding Bridgeport , there is now extra space where the water can go. Another benefit, it creates beautiful coastal habitat with walking paths for viewing seabirds. The govt has just released a big report on this , moving away from hard flood defences to more natural based vision. Nature is always best at protecting itself, things like mangroves and saltmarshes absorb the wave energy. Or go the other way, like in Dubai. advance the line the Palm island. In the Maldives they built an entitre island. We could adapt , to build floating houses , floating bridges and just live with flooding. In Bangladesh people want to live on the floodplain as its very fertile. As long as there is a good warning system. 2 or 3 days warning of flood due, they move livestock to introduced higher levels. Temporary low level structures get washed away , but they rebuild, and all are alive because of the elevated retreats. For our cities, build underground car parks which w ecan let flood . Q&A As the ocean levels rise, the amount of moisture in the air increases which cause white cloud to form and cools the Earth, as the clouds reflect sunlight back out. As temps increases it will reach a temp , might be quite high I don't know , that stabilieses. I'm not a climate scientist and know little of that, I'm very much #sea-level aspects. All I can say is SLs are rising and we can say which components are involved. The Grace? satellite up there can monitor water and we are finding more groundwater is making its way into the oceans. We are also finding the building of dams slows down SLR as water is stored on land, but a small component. There is feedback systems in the climate and a key feedback is the albedo of the ice, less ice absorbs more heat. Q: ? ? waves ? ? Its quite small , thousands of years. It doesnt affect SL much , it affects geology. The energy of the tides gets dissipated and over time that is causing the moon to move further and further away. But its very small, on our human timescale. Q: Remind us ? SL would rise ? About 80m , Greenland on its own about 8m and Antartica if all melted somewhere between 65 and 75 metres. A recent article shows that Antartica is gaining ice which they think has been preventing SLR. The main concern with Antartica is if a major collapse of the ice sheet. Warmer water is getting under the ice and if it collapses it could allow much more ice to move off the land, presently barred from doing so. If such a collapse then SL could rise several metres quite quickly. I've read recently that the gulf stream is slowing down, is that complicating the issue? 2 papers in Nature, I know both authors , both papers show that AMOC , of which the Gulf Streamis part of. Our climate is warmer than it would be without this, but over 100s or 1000s of years that changes. That won't affect SL that much but would have huge impact on our weather patterns. Interestingly it does affect SL off the coast of USA. The gulf stream causes SL at the US coast to be lower and higher in the Atlantic. With less current flow then less geostrophic flow . So SLs are rising faster along the American Atlantic coast as a result. A regional hotspot of SLR. What sort of temperatures required to get full Greenland ice melt? You wouldn't in hundreds of years. Take an ice-cube and double the temp in the room, even an ice cube does not instantly melt, it takes 100s of years, considering 3km thickness of ice on Greenland. A colleague in ANU oz, has a figure I don't remember what, something like 10+ deg , but sustained over 100s of years. What %ge of human CO2 emissions compared to natural processes adding to global warming? I'm no expert on the atmospheric side of things, from 1970 very large component. SLs can vary 5 or 10cm purely naturely by El Nino oscillations , changes in wind patterns and amospheric pressure changes. Perhaps 80 to 90% of the warming since 1970 is human source. Even if we reduced emissions, the other countries are coming up , far larger than us, and negate by many times what we will save.? A few months back I met with community leaders from the Solomon Islands , the Maldives as well, they have the lowest emission rates in the world, yet they are feeling SLR effects first. Whether you believe in climate change or not, SLs are rising. For 150 years its shown no sign of sustained reversal. 139 cities with populations greater than 1 million on the coast , climate change or not, SLs are rising. Soton Archaeology Unit has plenty of evidence of SL having risen by 5m in the last 5,000 years. Where does your figure of SLs being constant for 7,000 years come from? There are 2 components to SLR, absolute SL rise and there is relative SLR. I skipped that bit in my talk. You have to be very careful with this. Satellites measure absolute SLR , just changes in the volume of the oceans. Tide gauges measure relative SL, so SLR and also changes in the level of the land. In the UK we have isostatic adjustment . We think the land is stable but the land is moving. Think of it as a foam mattress, you dive onto such a mattress it sinks under you, you get off and it will take hours to recover. For the UK in the last ice-age 20,000 ya almost all north England was covered in ice. That ice melted but its taken tens of thousands of years for the land to respond. So northern England is rising because it was weighed down by the ice, the land rising about 1mm per year there, southern England is sinking. If you look at Iceland or Stockholm SLs are actually falling , not because SLs are falling there, its the land is rising faster than SLs are rising so locally it looks like its falling there. So what you have here is a very localised relative SLR of 5m over 7,000 years. Q: The hampshire basin itself is prone to sinking, the gravel terraces don't match across the South coast here, so you can't single this out from the isostatic rebound, its more complicated. One of the key localised contributors is groundwater extraction. Bangkok is a perfect example. Everyone in Bangkok has their own well and the whole of Bangkok has sunk by 2m. This local effect is 20 times the effect of global sea level rise. This is human change but not climate related. Tokyo has sunk by 4m . In Bangkok there ar esome telegraph poles that used ot be on land and now in the ocean. Unpicking these things is difficult. In Bangkok the local SLR since 1950 has accelerated massively. People though that was climate change, but it was just local land subsidence . They had to put a law in place not allowing wells , fined a lot of miney if they do and that seems to have stabilised that problem there. Itals occure in New Orleans, part of the reason the effects from Katrina were so severe. People get obsessed by climate change but there are other things , some can have larger effects. If you have a surge coming in off the Atlantic , so at Newlyn its say 0.5m above astronomic prediction and lets say its a neap tide, it comes up to the Isle of Wight and tends to be a bit higher locally here. For exactly the same circumstances, the same wind but occuring on a spring tide, would the surge effect component here be higher than the neap tide case. And extending on from that , with SL change , with more depth of water , for surges passing over , all else being the same , decades into the future, would the penetration over the land be more that it would have been before apart from the simple SL rise itself.? These are indirect effects , we call them tide-surge interaction. If you get 2 containers and blow over them. The wind is more effective on rising water when shallow than when its deep. This is why the North Sea shows serious storm surge effects as it is so shallow. This is why storm surges in the North Sea are much bigger than in the English Channel which is deeper. If a storm occurs on a neap tide , often the surge is bigger than if it occured on a spring tide. Not the total water depth of course, just the surge component. You often get this with huricanes and a surge at low water is mor eof a surge than at high water. Not the total water level , just the meteorological induced component. A storm surge travels as a shallow-water wave, its speed is dependent on the water depth . An equation square root of g * h , gravity and height. Raise the water level and the wave wil ltravel faster because its deeper. As SL rises it should actually very slightly reduce storm surge components , but as SLs rise , waves can break closer to the shore than before. Waves move until a certain depth and then break . Indirect effects, a lot of work being done on them, but all relatively small, cm not metres. Q: So we all move to Scotland? We've built in all the wrong places. Go on Googlemaps and look at Winchester, its on a river flood plain. Rivers are supposed to flood , its good for the land. We've built there , but the problem is we can't change that. I think the govt should have stricter rules on wher e you can build. There should also be law that any building on flood plains should be on stilts , a legacy problem. Q: If the gulf stream moves then Scotland could become permofrost? I was in a taxi and the driver said he will stop being a driver as he'd started an air conditioning business. He reckoned with climate change, mor epeople will want AC, he was genuinly serious. I could have told him that globally there wil lbe climate change but in the UK , perhaps a shutdown of the gulf stream and drop our temps . AC in the USA is one of the major energy consumers , hence climate change? When living in Oz I had an office with AC , 35 deg C outside and I was wearing a jumper inside, such a waste of energy. In the states its quite common for them to literally move house. Has anyone managed to jack up a house and mount on floats and dolphins a standard brick-built house? They've done it in Chesapeake Bay. A house that has been destroyed about 10 times in the last 20 years but it always gets federal aid to rebuild it. to me thats criminal , say flood 3 times and then no more aid. Its easily to talk here about this, but if you've been flooded its an horrendous experience. If I lived on the coast I probably would not want to move and be very annoyed having to pay off a mortgage on a house that fell off an undermined cliff. There are some examples in the Thames Valley , rich people, who've done exactl;y as you've said. Brick built buildings, completely underpinned and mounted on hydraulic jacks . If you have millions you can afford to do it. They are fixed to a base thats in the ground , jacks in place and instead of floating, they are jacked up as required. An Eel-pie island one is a house in a tank , and as the tank floods from the Thames , the house floats up. Some incredible engineering around, in Japan there are gates that self-close . W78

Tuesday 15 May 2018 Bob Stansbridge , Soton Uni: Micro-Electro-Mechanical Systems (MEMS); what they are, what they do and why they are jolly useful. 1.5 hours I lecture in instrumentation to mechanical engineers, aero and ships engineers. When I started at Soton Uni decades ago, I was in the highest tower the Faraday building. I was involved with 2 people working at the top of the tower, manufacturing integrated circuits, sub-micron lithography, geometries on silicon less than 1 micron wide. A big advance at the time , but the tower was too wobbly and they had to move the plant out. Every time the lift moved, they could tell . They were working on making shapes out of Si , using the same IC manufacturing techniques , etching and depositing materials, removing or building. One was making a cantilever, like a bracket hanging off a wall. So they cut out a shape and then eroded underneath. You could see the little structure on an electron microscpe, but said its a pity there is no use for it. But there was a use for it, accelerometers. A visual aid of a happer on a string, the hammer is the proof mass and the bit of string is the meter. Move it slowly horizontally and the string stays vertical, but move it quickly , then because of inertia the mass stays back, and then catches up. Soif i could measure the angle , then a measure of the acceleration. The bigger the angle , the more acceleration. Put a mass on a cantilever and if you've a way to measure the bend , then a measure of accelertion. Not much use for them , then. A major use was crash-test dummies. Newton's second law F=m*a. So a dummy of known mass, given a known deceleration and measure the forces. The old style acceleraometers were a mass set between 2 piezo-electric materials, in a can 12 x 12 mm or so. One side is squeezed by the mass , when accelerated. Squeezing out a few elecrtons a few microcolombs. They cost about 250 pounds then and involved a special charge amplifier , that cost about 350. Very few were made , as only specialized use, so very exp[ensicve. They were highly specified, each with its own calibration #curve , frequency and temp response etc, all traceable back to the NPL. So 600 pound to measure acceleration on 1 axis. The were exploring a cheaper way of doing this. Another use was to take one of those cans and stick on on the side of an engine or particularly a gearbox. When running it would shake and you can measure the vibration of the casing, condition monitoring. A frequency spectrum wiht picks corresponding to cogs rotating at different rates with different gear ratios. Something big likand expensive e a turbine can have its condition continually monitored likke that. A chiped gear , or a lack of oil will show up in the vibration, knowing the construction of the gearbox. They can then do preventative maintainence. The first use of the MEMS version was in air-bags. They got yhe price down from 600 pound per channel down to 30 pound. Also mounted in top end cars, not requiring high spec, just detetecting hitting a wall say. With this extra use, the price droppped to about 8GBP. Now they were that cheap , they could go in games consoles, the wii. They are very small, and now in gaming machines , the price dropped again. They went in mobile phones and the price dropped again. So now you all cary one around. From the silicon, a central mass remains after etching around and under it, leaving 4 corner supports, hanging in space. There is air inside, that acts to damp. A visual aid , large MEM accelerometer. A shallow wood box , a central plate supported by 4 springs to the corners of the tray. A pointer fixed to the central plate and a scale on the left and right. Move quickly and the mass and pointer moves relatively to the tray. So how much force involved with moving those various amounts. Turn it throuhg right angle and gravity is acting as a force and the pointer moves to +1, turn upside down and it moves to -1 , a change of 2g. From that I can calibrate the rest of the scales, quite a simple calibration procedure. So how to measure the tiny movement electrically. Less than 3pF capacitance, and the change is about 1 part in 1000. No chance using a capacitanc emeter. Instead of 1 finger, produce a comb of fingers , 100 times the capacitance. Dimensions of the electrode combs about 30 microns. We cannot measure the movement externally , it must be done internally. The combs are about 100 micron long, 3micron deep and 1micron between fingers. The central mass weighs 1 microgram, so a millionth of a spoonful of sugar. They put a simple oscillator in there, gives pulses, 2 sets of pulses , one upside down relative to the other, anti-phase. Because the fingers are so close, the effect of trhe signal can jump across. The fingers move closer to the A electrodes, so picks up more of the A signal, amplified gives +5,+5.... +5. If its in the middle , its about the same for both sources, roughly midle when amplified. Go the other way and B signal is transfered mainly, giving 0V when amplified, just for the few moments when accelerating. This amp and demodulation circuitry and some comms circuit is all inside, nothing outside except some power source. Why didn't they measure the resistance of those very fine corner supports? The advantage this way is its differential and very linear. Q: what is the frequency response? Its very high as they are so small and light. With the old piezo type they would not do low f at all, a flat response except for an enormous resonant peak , they had to stay away from. Something like 100 or 200KHz, mainly limited due to the speed of demodulation. As they are silcon , then the same temperature limitations as transistors etc of about 150 deg C. For any app hotter than that then piezo or strain gauges, or capacitance. You can add extra combs around the sides, but for a long time were stuck wiht just measuring x and y, eventually they could introduce z. But as they are so small they could just place 3 orthogonal together. That is just the beginning. Moving from a to b , say just a metre, you have distance and time. If it took 1 second then the velocity is 1m/s. So keep on measuring tme and distances you can work out velocities. If you know the vel at point c was 10m/s and at d was 12m/s, then you know it accelerated 2m/s per s. You can go the other way, knowing acceleration , you know hte time those readings were made, you can determine the velocity, then with velocity you can work out how far its moved. So now with an accelerometer you can tell what forces there were, the accelerations in diffefrent directions, the velocities in different directions and how far you moved. So a navigation system. So electronic op-amp integrators , doubled up, integrate a to v and then v to distance. These days that integration process is done purely mathematically in a microprocessor. Such as this is called an IMU, inertial measurement unit, to measure x,y and z plus other things. Add a memory card to it . A video of someone with one fixed to a shoe. He walks along straight, climbs a spiral staircase and walks 10m on the upper floor. Showing the vectors of each footstep. Q: so a small stone in his shoe, changing his gait , would have shown up on that plot? Yes Another app, a version placed inside a ball , for measuring turbulent flow in water. It stores all the movements on its memory card. Its called a smart ball, footballers use it. Another app, a gyroscope. Also twisting movements , measuring the rate of change of angles. A barometer using much the same principal, or an altimeter because of change of pressure with altitude. In 2007 Albert Ferrer and Peter Groomberg awarded the Nobel prize for dicovering giant magneto-resistance. Current flows more easily in a layer aligned with the direction of magnetism With a very thin layer of metal , not a piece of wire as the wrong scale. They could do that inside a MEMS device, so they can tell which way is north. If it turns over , they can still say which way is north. With 3 of them,x,y&z, they can tell which way is north in 3D, a 3D compass. It always knows which way is north and always knows which way vis down regardless of which sense itself lies. Its called an IMU. So its a navigation unit, so on planes, space vehicles and satellites. The one with me is 3 axis accelerometer, 3 gyroscopes , 2 magnetic sensors, pressure sensor, 2 GPS receivers. Even sophisticated GPS receiver has to know which way its up. Initally these cost 800 GBP for 1 accelerometer measurement. Now you could buy a MEMS accelerometer, 2mm long, 2mm wide, .5mm thick, with 10 degrees of freedom, x,y,z , pitch,roll and yaw, 3 axix magnetic sensor and temperature, so 10 columns of numbers come out and it cost 95 pence, if you bought 1000. It had an incredibly long and detailed data sheet. It could self-calibrate. Its all microstructure , no coils . For the magnetism its like a barber's pole, the conductor in a helix. Dependent on its orientation ,makes the magnetic field spin. With those things you can involve feedback. A single gyroscope with a servo system, so turn the unit and a follower moves in sympathy elesewhere, with no observable latency. A quadcopter demo of stabilisation using an IMU, with the numbers coming off the IMU with and without stabilising. Without, a human finds it impossible to control. Another example , balancing an inverted pendulum on the top of it while flying and also a glass of water. The numbers showing angular velocities and angles in degrees, pitch roll and yaw. You see drones all over these days, because motors have been around for ages, but batteries are lighter these days, and of course the introduction of IMUs. You can use such systems under water or underground, where there is no GPS or even in a warehouse without GPS inside. There are problems with it , but a basic navigation system on board. They are ordinary motors but pulse-width modulation powering. You can use them on UAVs. These aren't precision scientific type units. The microcontrollers can be built in there also, and so cheap. About 50GBP but cloned versions are about 3GBP. Another curious use, reforesting. Send a drone up with a pack like a dart with soil and fertiliser in around each sapling. Drops it like a dart penetrating the ground. Can reforest a big area done remotely. Yesterday I heard that in Leeds doing an experiment . Over a million GBP in Leeds mending potholes. The potholes only got repaired after damage to car suspensions. They will use drones to scan the road surface for defects. On finding a defect, the drone will do a sort of 3D-printed patch over it. So they fix the pothole before its become a pothole proper, so a lot less expensive. Doing it at night avoids holding up the daytime traffic. Now the fit-bit, not just for the fit. Old people's home with a new alarm system that monitors all human movements carrying a sensor unit. If someone doesn't move then someone will investigate. Q&A Worst case of these sensors in a mobile phone, if you drop it on concrete , the screen survives , would the MEMS cantilever component survive that sort of high g direct impact? They are very robust, they can take something like 100g. The cantilever is no problem , its about 1 microgram. Its like you could drop a mouse off the Empire State building it might survive, as very little kinetic energy there. Thats not MEMS failure mode . That jet-pack man or Iron Man, I keep saaing video of, I bet he has a few MEMS in the control of that, considering 3x 200 horse-power thrusters on each arm? If he puts his right arm out , then he should turn over, but there must be stabilisation on there to bring him back up again. ? ? calibration ? You don't have to tell it where north is, it will find it itself. There is metal around and also lots of stray magnetic fields from motors etc. So they would tell it where it is , before it takes off. There are hard magnetic fields and soft magnetic fields. Hard would be from a magnetic material, and like a compass needle , would affect the MEM. With variable fields from the motors, they would calibrate it at the start. With the gyro and the magnetic field sensor , if the gyros say a test turn has turned and the compass says its turned, it has turned. If the compass says its turned but the gyros say its not turned , then its not turned. Al lthe fixed magnetic fields will still be fixed, it will see north fluctuating as it turns, and they can work out which field is the Earth magnetic component, and what the othe rfields are associated with the structure its mounted on. It is a problem and its not fool proof. Bu tthere are techniques to imrove the situation. Could they put it in a mu-metal box? They don't really have to . The sensing element is a mechanical structure, ? ?. How do you get tiny GPS receivers, on a tiny chip, surely some sort of largish antena is required? Yes there would be an external connector to an antena, beyond the chip. How GPS works , is satellites with high precision atomic clocks on board. They transmit the time and with 3 satellites minimum in view, you can get a 3D fix of position. They all transmit a code containing the time . The receiver picks them up at different times , whether near or far, then the speed of light , works out how long the radio wave took to travel. The intersection of the circles each radius being the transit time from each satellite. Nothing is perfect and with 4 or more can get a better fix. The use of MEMS with otherwise mainly GPS improves things in the areas where there are complications for GPS, in urban environments etc. Threy can correct each other. S 17

Tuesday 19 June 2018 , 20:00 to 21:30 St Denys Community Centre, Main Hall, SO17 2JZ David Johnston (Light Microscopy Facility Manager, Biomedical Imaging Unit, University of Southampton and University Hospital Southampton NHS Foundation Trust) Small is beautiful. Microscopes, sample preparation and imaging technologies have all developed rapidly in recent years, allowing us to look at biology in ways that we previously never imagined possible. Show-casing the different sorts of microscope technology available for biomedical research (using light, electrons and X-rays) and the many types of multidimensional image data that we can generate. 1.5 hours Some of us in the unit are NHS employees and some the university. We all mix and match supporting both sides. So most people have tried school type microscopes (M), and could barely see anything. They don't focus properly, smeery images. You can pick up reasonable Chinese made instruments these days for about 100 GBP and they're not bad. The ones I will be talking about tonight cost between 50,000 and 250,000 GBP. Orders of magnitude better and in terms of what they can do for us. Size and scale. Take a mm and expand it up , microns or a millionth of 1m. Simmilarly diividing a micron , to 1000 nanometres a billionth of 1m. Scale - an Airfix kit 1:72 scale, buy 72 of them , stick them end to end, be the same size as the real thing. If we represent 1 micron by 1m in the real world , starting from here we'd get to Paris. Go to a nm, and go from 1m in the real world, around the equator 25 times. We can magnify anything by as much as we want, but we get no reward going higher, we see no more detail, we same the same detail but just bigger and more blurry, we've reached the limit of resolution. So resolution relates to how small things are and how close they are and we can srtill see 2 separate objects. Different biological effects occur at different scales. The very best eye can only see down to 1/250 inch , for most people its 1/120 inch. So we go to Ms to enlarge and get better resolutuion. There is a limiit on mag of optical and to go to smaller scale , we have to go to electron Ms. The unaided eye can see down to about 250 pixels per inch. Apple retinal diplays are 326 pixels/in , you can't see it. The new Sony Xperia S5 is 806 pixels/inch, completely pointless , its a marketing tool. What limits our engineering ability to make good lenses- its the laws of physics. The human eye can see light from deep blue to far red 390 to 700nm. The limitation is the wavelength at which we observe thigs. The resolution is about half the wavelength of the red light. So things closer than 200nm , 1/5 micron, we cannot tell apart by the very best light M. To go further we have to use things with smaller wavelength. Its not our abilities to build good M that limit us. We can do some clever things with light though. 2 basic problems of observing biology with light. Most biology is composed mostly of water , we are about 67% water, about 80% for muscle and 30% for bone. So mainly transparent , so most biology is transparent. So how do we see tsomething thats transparent. The next problem is engineering, we cannot make the perfect lens. Every lens has a point at which it focuses, but it still captures info from both in front and behind that point , but out of focus. So your focused bit is always superimposed on out of focus stuff either side of it. So you can never see everything fully clearly, whether a lens in a camera, telescope or M. The human eye is a bit different has it can continously adapt focus, for different distances. To get around this, we can make our samples very thin, so the thickness is what the lens can hold in focus at any one time. Usually our samples are embedded in a wax block and then cutting very thin sections from it, that roughly correspond to the focus range ability of the lens. A piece of human tonsil about 5/1000 mm thick , originally a raw red colour but cut it down to that thin , 80% water and its effectively transparent, w ecan't see it. Counteract that by usually by staining with a cromatic dye , giving it colour to be seen by. Thousands of dyes available but all are pretty limited and crude. Purple on the nuclei , pink is the cytoplasm , we get the gross structure but not any real detail. Even the best dyestuffs, a combination of 5 stains, w ehave more colours there, but its still relatively crude as to what its labelling by the colours. Q: The dye is just saturating the tissue? All the dyes have slightly diferent specificity , one pair could be haemotoxin and diosin, H&D is the most common one, The H one tends to go into the nuclei of the cell and th eD to the connective tissue , cytoplasm . With the pentachrome, 5 dyes, one would go for elastin and collagen . They are crudely selective like that, they've been around for centuries, very good what they do but very limited. For a piece of lung tissue we've had to fix it, kill it , dehydrate it , embed in wax, cut thin sections, stick to a slide, get rid of the wax, stain it, dry off again, pedastal? on top , and then ready to look at. Can't do that to observe living material as it killed and preserved. To view living cells grown in a nutrient soup , we come back to the problem that biology is transparent. No contrast in the cells, we see nothing. Phase contrast microscopy gets around that, producing contrast in transparent material by changing differences in refractive index, how different bits of cells bend light. Using a trick in physics to do that. One of our phase-contrast M. Its built upside down ,, for technical reasons, an incubator housing around it, so we can grow cells in there and observe them ove rlong periods of time. A video of how cells in a body move around. A sheet of epithylial cells, lining cells, from the airway , grown into a confluent sheet, then we put a scratch in it. Cells don't like that space, they grow into it and when they touch from both sides they stop dividing and stop growing. A sort of model of wound-healing in a body. The trick we use is the back lens of the objective on the M , that does the magnification has an etched silver ring that blocks light. On the condenser bit of the M, that focuses the light onto the sample, there is a blocking plate with a circular slit in it. Matched and aligned with the lens etching. Nothing gets through until you put something between them , that bends the light. So quite simple in some ways , but it works very well. Another trick is to use polarised light, same as in polarised sun glasses. A polarising filter , it restricts light to light vibrating in a single plane. Place 2 such together , that are crossed, cross-polars , no light passes as what passes one is blocked by the other. Unless you put something between them that has a highly organised structure of crystal. If you use crystals, crystalised out on a slide, you get stunning pics. Some parts of biology have a suitable structure, like collagen, the protein strands line up in a precise controlled way, a sort of pseudo crystal and bends light that is polarised. A pair of images of lung tissue comparing to the polarised view which shows where the collagen sits. With high mag , we can only seea small section at a time. We can do "google-earth " with M slides. We have 2 types, one that will do up to 4 slides at a time and another that will do 100. A robot loader that picks slides out of trays, loads them in, the M has a very precisely movable stage that can take 1000s of individual pics , covering the whole area of the slide. Then use auto-stitching when asked to look at a certain part. A piece of spinal cord, comprising 2500 individual pics , then with a web-browser type set up , we can zoom in where required, jumping around. Low bandwidth required as only the bits of image interest are manipulated when required. One uses a very high quality digital camera with lens with no spherical aberration. There are line scanner ones that are much faster, that traverse the whole slide in a scan. So we make a slide from some piece of patient anatomy, with a problem that we don't know what it is. Someone on the other side of the world with expert knowledge can help you zero-in on a diagnosis of the problem, without the use of large bandwidth pipes. This is what is useful in our context. We still use the same sort of staining and slide preparation. It allows us to produce digital archives, relating to rare metabolic diseases. We can make them available asa teaching resource. Much more freely available than a physical slide in a lab somewhere. Instead of using chromatic dyes we often use flourescent dyes now. Chromatic dyes are very non-specific in their staining , but we can make FD almost any colour we want, that are highly specific. Often they are involving antibodies. You go to your doctor , for a flu jab , you will be injected with a deactivated flu virus. Your body can then produce an immune response to an assault. Antibodies, very specific proteins, have a lock and key relating to that protein and that protein only. So essentially we purify the protein we are interested in , inject into a mous eor a rabbit, it is recognised as foreign , produces an immune response to it , take a blood sample and find antibodies in there. Put them on some tissue that has that protein and the ABs will bind to it with a flourophore?, exite the flourop[hore and can see the sites. So very specific localisations. You can use multiple fluourophores , for multiple diferent targets, and a good range of colours. So image of heart muscle , with bands of contractile protein in it. Another pic is a piece of spleen where one group of immune cells have been labelled up and nothing else. Everything so far is 2D, but biology is in 3D. Q: ? Different dyes are excited by different colours, but always give off a red-shifted colour. We might excite with UV and get blue light off, or excite with blue and get green light out, or green in and red out. It depends on the dye and we can pick and choose what we want, deppendent on the requirement. To go to 3D we have to remove the out of focus part that is super-imposed on the in-focus. No trick of p[hysics required. So for focussing on the nucleus of a cell, we also get light from above it and below. But a form of m, called confocal-M , sticks a plate with a tiny hole in the light path. Then only light from one level gets focussed at one viewing level. So we can produce an op[tical section , then refocus slightly , and repeat and producea 3D dataset. Ech slice of the datasetr is just the in-focus bits. So for the nucleus image now, we so nothing of the organelles above or below it, or we can move to the organelles levels. It works with laser beams to do the excitation , different colours, bent into the M light path and 2 mirrors in the head that oscillate in a very precise and controlled way, to doa tiny scan across and down. Any flourescence wil lcome off and some will go back into the M, past the mirrors as differnt frequency of lightr, dichrome splitter, past the pinhole and on to the detector. The detection is just a light intensity meter rather than pixel array. But it knows where the surveyed spot was at any one time. So builds the pic, lightness values 1 pixel at a time, but very fast. So any ordinary M viewing parts of a worm , we can see there is different stuff , but we never see it clearly , because of the superimposition of out-of-focus stuff. Looking at the same 1mm thick sample by confocal-M , layer by layer, out of focus stuff is rejected and nice sharp images. In response to the flourescence light coming off at different colours , glows from different probes in there, the light is split by prism intio a rainbow, focused by lens systems into parallel light paths and one of the light sensitive meters sits in front of each path. Before them are 2 mirrors and the gap between them , can be opened and closed, up and down . So the gap is moved across parts of the colour range , corresponding to each flourescence colour of each dye . Anything that does not go thru the gap bounces away. Other optical set-ups in the other detector paths. so simultaneously we can detect 5 different colours, with infinite tuneability and nm precision in terms of the wavelength of those colours. It is really easy to use, just manipulating slider bars on a pc screen and the actual manipulation is done behind the scene. It allows us to look at lots of different things all at the same time, very specifically. Some new stem cells grown in culture, stained with 4 different flourescent dyes against 4 differenr cellular components. Blue is DNA stain of nuclei , a stain that is active antibody to a protein that only occurs in the nucleus of some cells, the white, then 2 antibody stains that recognise different proteins of the cyto? structural scaffolding. The filaments, one labelled green and the other red, and different cells express different amoints according to what they are doing. Some green , some red and some between of orangey yellow, that are expressing both. So by repeated digital slicing we can get multi-section 3D datasets. The head of a tiny shrimp, going through it , section by sectuion just by moving the M focus on the con-focal. We can take all those images , kind of squash into 1, and can see everything in one go. You can see individual muscle block for individual joints, in all about 2mm long. Another job, with the NOC, looking at mudstar fish, living in the deep oceans. They burrow into the mud and eat fallout from upper levels. They are interested in how they reproduce. As they are in the deep dark ocean, do they give off environmental signals. They reproduce all year round as no seasonality or do they have to have seasonal reproduction. We are looking at the ovaries of these and counting , via confocal M, the number of eggs and what stage of developement they are. Because its a 3D dataset , we're not just restriceted to looking up and down , can look in x&y, x&z etc. We can manipulate the data set to look at any angle and that is very powerful. Vey early mouse embryo cells, about 1/10mm diameter, but they've started to develop. Stained with 3 flurescent dyes, 1 for the nuclei as blue, and some as green a marker for one particular cell fate? , and red for another cell fate. 3-D veiwing glassess , red over left eye and relax eyes and can see the 3D effect of the video clip. If we have a 3D biology dataset . This is blood vessels ina brain, injected with tiny flourescent beads. Some are closer to you and some farther away. Part of a study looking at Alzeimers and neuro-degeneration and changes in brain vasculature. The tiny capilliaries of a human placenta. Another type of M is light sheet M, where excitation lighting is shot from the side, very thin but wide band of lazer light to optically flouresce. We make our samples clear , sitting in a bath of organic solvent that makes it transparent, light from th rside . It only excites F at a particular level in the sample , capture with camera at the top and move the sample . This is much more macro in scale , up to 1cm x 1cm. The whole head of a mouse, starting from scalp top . The F for this was a specific probe , for neural pathway of the brain, we can isolate just that signal which is green here. Again as 3D dataset can be manipulated any whichway. We can also do cool stuff with electrons. We are still limited by the rules of physics and how close we can get and see things apart. So for snaller dimensions than the wavelength of light , we move to electrons, that behave as waves but their wavelength can be up to 1 million times smaller. 2 forms of electron-M , scanning e-M a source of electrons at the top , a variety of electronic lenses in the vertical colum that focus the beam and scans across the sample surface. The sample is in a chamber at high vacuum. Sample fabrication is difficult, must be fixed , chemically killed , preserve it, dehydrate it in a precise way so it doesn't just collapse. Any water in the vacuum would just boil off so must be totally dry. The surface must then be coated with a very thin layer of gold or gold/palladium mix . The electron beam , as it scans across, interacts with the coating, bouncing off and be detected or hit the coat and generate more electrons, secondary e that are also detected. So we get surface views, not internal structure. The great +, is it has incrredible depth of focus , close and distant parts are held in focus at the same time. A x400 pic of a dandelion seed, and a great depth of field, that is achievable by light-M. Go closer x1200 can see individual pollen grains , about the limit of light-M. So moving to e-M, individual bacteria at x7000, and at x14000 the surfaces of individual cells, the processes are micro-vili, and long thin processes are cilia. Little motile structures . On our e-Ms we can go to about x60,000 but only of surfaces and because electron beams, always monochrome. The images you see in the media are false-coloured, to make different things stand out. A small airway in the lung, red blood cells, and cillia on the cell lining the airway, the mechanism that keeps the lungs clear of grime. Q:How is the false-colouring done? Basically photoshop, masking out different areas , so entirely manipulated . The other type is the transmission e-M, pushing e-beams thru a sample. To do this with e, we have to make the sample very thin. Start with tissue sample, chemical fix it to kill and preservr, embed in block of resin so about 1mm cubed . Trim that black down , then with often a glass knife . Take a long strip of glass , cut into squares across the diagonal, and get incredibly sharp but short lived knives. A plastic boat around that , sealed with wax and fill with water. Then a microtome, a sophistacated very thin slice "bacon-slicer" advancing minisculy onto the knife, we get very thin slices, of the order 50nm. Essentially about as this as an oil film, very delicate and very skilled handling required. That needs to be picked up on a tiny copper grid , stain wiht heavy metals , to give contrast in the e-beam. That sample goes on a rod that is entered into the e-M through an airlock, into the column. We shoot the e-beam thru the sample , with mags up to x200,000 . Goijng up ins scale, start with clls of the intestine, the absorbtiv e layer, one cell ith its nucleus , a goblet? cell producing mucus, includes gland filled with mucous. A big surface area for absorbtion, mag x2000. Up-scale a cross-section thru one cillium , much less than 1micron across and can see discrete structure, x50,000. Individual virus particles , x200,000, a sort of cross between a hypodermic syringe and a moon lander. A head with the DNA in it , then a needls and a contractile outer sheath with legs. They land on a bacteria cell , with the legs stabilising it, the contractile bit contracts to force the needle thru the bacteria wall into the cell, to pass the DNA thru. If I took a peanut and magnified it 100,000 times it would cover the centre of Southampton. Back to cillia , very complicated internal structure, individual linked tubes , hair like wafting in a controlled way. An efector stroke and a recovery stroke , lining the whole of our airway. Every time we breath in , we breathe in dust , bacteria etc. If left to accumulate in the lungs , would clog them up and cause infections. Many of our cells produce mucus, so dirt is trapped in the mucus and the cilia , wafting in syncronised fashion move this dirt al lthe way up the airway, 24/7/365 to the top of the windpipe where its swallowed and then neutralised in the stomach, for the entirety of our lives. Its a complicated structure with hundreds of different proteins involved in it. Any mutation in any one of those proteins , can effect how those cillia function and the lungs don't get cleared well. A spectrum of diseases that come under Primary Cilia Diskynesia? where scilia don't beat as they should do . Another M technique is high speed video. Scilia on the edges of a small group of cells, healthy cells from a normal healyh person. A tiny mascarra brush is pushed 6 inches up into the nose. Scrape out some cells , place in nutrient so we can view at 500 frames per second camera and high mag. The scillia are all wafting in a co-ordinated way, over the patch of cells. Q : Do the cillia rotate as well? Not the ordinary funcioning cillia . A longer cillium is called a flagellum , like the tail of a sperm . Bacteria have a flagellum that have a different struture and some of those do rotate and twist. But in higher organism its a beat and recovery stroke . An abnormal scilliun can do that or be still or be hyper-active, but normal ones are effector then recovery stroke, like a rowing action. I don't have pics of rotating ones, but an abnormal set from a patient with PCD, they are not beating efficiently, out of sync with each other , not a nice regular stroke. This is part of the dignosis of this disease. We are 1 of 3 centres in the country to do this , looking at high speed video. We go beyond that to look at e-M , as often bits of the internal structure is missing, depending on the overall genetic cause is underpinning . Outer tubule doublets in inner pairs and linking arms , which are like the motors , link tothe next and cause the bending. Some patients with a particular genetic mutation of their genome, bits of that structure are missing or disorganised . It requires very high power e-M to do such diagnosis . But sometimes these differences look perfectly normal by ordianary e-M. This is where we do e-M tomography. We take a thicker than normal section , image it in the e-beam and then tilt it , so we get views , of hundreds of cillia fro ma patient, average them all together , make a 3D model based o nthat data. An outer doublet with 2 dynime ? arms, 2 motor arms on it, fro ma normal patient , from yomography. The outer dynime arms of one is solid . In a patient where we know the cillia ar enot beating normally , look normal by normal e-M , do tomography on that patient sample . As we tilt the view we can see a hole, that is the mutation that exists below the resolution of normal x150,000 e-M. But with this extra trick , we can see what is going wrong. TEM is complicated , 3D biology , a 50nm sample of tissue, but what is going on above and below, we cannot tell. Whenwe remove that string of microtome sections , we cannot recover each slice intact, process it, register it, all in sequence is virtually impossible to do. We can get a 3D image of e-M, combining scanning and transmission e-M, called serial block face scanning M. A very high quality scanning e-M , with special sample chamber that includes a mirotome , slicing machine, with a diamonnd knife, that lasts for years when looked after. Take a sample and prepare as for normal transmission e-M , this one the sample goes black because we use osmium , combines with lipids and turns everything black. That 1mm cube , mounted on a pin near the diamond knife . The cut sample is scanned by e-M, that slice is chucked away , image again , throw away and repeat this for thousands of sections. Because we don't need to recover the section , that is fine. So allows us to do 3D biology with TeM. It allows us to look at stuff we could not look at before. We can let it run and do thousands of sections. Bone marrow cells in gel, visualiesed by serial block face. Going down cell by cell with perfect registration with all the detail, phenominal bit of kit. Q:The gel is transparent? Its completely black but transparent to electrons. Its stained with heavy metals that interact with the electrons, to give the signal. They were embedded in gel before being embeded in the resin to hold it all together. They came out of the marrow as single-cell suspension , then packed together, surrounded by gel to hold together and then fixed and processed to be embedded in the resin block, to keep it all tight. . Phenominally com[plicated datasets and no compute rcan analyse that . AI and patern recognition is not yet clever enough to look at something like that and be commanded to find a nucleus and segregate the nucleus of each of those cells, out from all else. It requires a trained biologist who knows what he's looking at to do that. It is laborious requiring step by step , each slice, drawing on the screen the things you want to segment. The initial dataset can take a week t o generate and then a year to analyse. So a whole PhD can be done on 1 or 2 datasets. Now a single cell from within bone, an osteocyte, segmented manually at multiple different levels. The nucleus, the mitachondria the energy factoies, the cytoplasm of the cell then the exciting bits are all the processes. Tiny holes in the bone, never been seen before. Not just visualising , you can do constructive maths on this the important bit of the analysis. X-rays, in terms of wavelenghth , fall between light and e-M. The resolution isn't better but allows us to do clever stuff. A regular medical Xray image, Xray source and a detector behind the point of interest, film or these days electronic sensor. 2D slicing of stuff that is high contrast, we can see the bone but not the muscles other than diffuse blob. Bone has lots of Ca that blocks Xrays. We can use a CT scanner to view patients in 3D, just a glorified moving Xray machine. Xray source and a patient and a detector and the whole lot spins round as the patient moves thru the Xray beam. By taking loads of images at different angles , we use a computer to generate the 3D appearance, Computed Tomography. In the lab we can use micro-CT, instead of movin ghte detector and the source, we rotate the sample thru 360 degrees. Even sub degree, for a dataset , then analyse to wha tthe whole lot looks like. This image I'm not allowed to show the inside of it as its the only one in hte country, made by Nycom? I think in the UK. The source and detector are designed to work with much softer samples, much lower contrast. There are micro-CT in the main campus where a whole jet engine can be scanned, very hard Xrays, to penetrate inches of steel or aluminium. Our tissue samples have very litle contast to Xrays. Its still a prototype and we're still working it up . A slice of human lung tissue , embedded in wax visualised and then #analysed to see where the blood vessels and lymphatic vessels are and segmented them out from the CT data. Then you can do maths on this segmented dataset, the important stuff. Then she modelled fluid flow of the blood vessels to work out the functioning in the lung. From the images, a mesh that can go in different computational resources and work out where the fluid flow goes in that bit of tissue. Q: some sort of doppler system to determine the flow? No its computational modellling, not measuring real flow , plugging previous sampled flow data into that dataset. It allows real measurement and do predictions as well, not just producing beautiful and complex images. We have all that range of tools in our unit , we have some of the best toys in the country, its a great job. Q: With the e-M, to get the electrons to move requires a charge, a high voltage, from the anode, what sort of voltage? Depends on the magnification, for low mag 12 to 20,000V, then # up to 200,000 volts, required toforce it through the tissue. Q: the anode is on hte other side of the sample ? There are electrons above and below . Q: The reflection M, the anode is on the sample itself? No it sits ou tto the side, but as the electrons scan across it samples the intensity of the signal doming off, millions of times, to produce the image from secondary emission a pixel at ta time. So 2 modes of operation. Often we coat the sample and get the bounced off electrons. But use a carbon coated sample , requiring earthing again as it charges up, but generating secondary electrons within it , also Xrays generated and different elements wihhin generate a different spectrum , for an elemental composition map across the sample. Q: do they do M with gamma-rays these days? Anything that has a wavelength you can functionally use, will be used by someone somewhere? Q: The Diamond light machine is something completely different to any of your machines? That uses a synchrotron, we can do a similar Xray procedure but ther's is massively hard energy and much highr resolution. Q: So you can see better with e-M, than Xray? In terms of resolution , yes unless you were doing things like difraction crystallography. Say a purified protein in crystal form , then Xray source and the scatter pattern, then deduce dimensions from that, a completely different process ot us. We can do that sort of thing on our eM. Big processing power? Our 2 main workstations for these datasets are 30core with 200G of ram, serious computer power. Often we have to go to a mainframe though. That is a limitation, the cost of RAM as its being bought up for crypto-currency mining. Q:The pressures in the chamber, of the order?, and you talked about gold coating , but the stability of a sample at such low pressures must also be key or you would get breakdown? Its pretty stable, once they've been dried in the appropriate manner and coated in gold , they will last for years. What you do find , if a complicated surface topology , like spikes, you often get discharges due to them and a flash bar on the image. Q: But generally not deep in the samples, instability at such low pressure? No because it must be porous enough, that as you take the presure down it can accomodate that, but has to be completely dry or it would boil off. The scanning e-M can operate in low vacuum mode and also in environmental mode as well , but only for samples that will not be destroyed by that, so usually high vacuum mode. For serial block face imaging , because of charge build up on the resin block , the resin is not conductive ,so impinging electrons have no natural earth path . The top slice is thrown away but charging can be a problem. So using a low vacuum mode allows the charge to dissipate through the residual air. A year or so back someone came up with a mod , which is a extremely tiny jet of nitrogen on a sling-arm, so when the knife moves back out the way , a tiny carbon fibre needle goes close to the sample and a tiny amopunt of gas to neutralise. That has revolutionised the quality of images we can get. The contrast under high vacuum is many times better. Q:With your 5-way optical splitting process , if in conjunction with an incubation chamber , presumably means cycling through temperature regimes, do you loose calibration ? Normally we would not be deliberately cycling through , we would turn the incubator on the day before, so everything is temperature stable. But yes, small changes in just room temp would change the M stand very slightly and can have an effect. Its not so bad with confocal , because of lots of ?, lots of slices at each time point and that will largely ??. With ordinary phase-contrast M, it can be mor eof a problem, room temp changes can move the sample by say 1 micron which is enough to go out of focus. So we heve ? that will rack up and down, record the images , looking at the changes in contrast and find the sweet-spot and use that one. So all kinds of add-ons. Some systems use a reference laser beam onto the glass at the bottom of the culture vessel and back down to capture the sweet spot instead. Q:For the movies of the beating scillia , what sort of M for those? Thats standard phase contrast M at x1000 , 50fps on very fast cameras. You can have high quality cameras or you can have fast ones. With such high mag , very little light is going thru, then you need an ultrasensitive camera, that is fast, so its not a cheap camera, about 10,000 GBP. You can tell all the different beat patterns from such images , fast Fourier analysis on the moving patterns on the sample . Q: what is the maximum mag you can get with light? The max useable mag is roughly x1000, x100 on the objective and x10 on the eyepiece. You can always mag more but you don't see more, jus tthe same stuff bigger and mor eblurry. Q: On such limits of viewing, in the early days of astronomy, when the optics got good enough to observe features on Mars, Hershel or whoever saw canals on Mars. Apparently that was due to night vision, the limit of resolution of the eyes and total internal reftraction in the eye or something, his brain interpreted the veins in his eyes as canals on Mars. Do you get the same sort of business with M at the limits of eye resolution , the brain seeing things that aren't actually there? Not that I've ever noticed , but you've got me worried now.;-). Normally that would not apply. Lookinvdown a M you sometimes see floaters , old red blood-cells floating across your retina a sa shadow and that is more marked down a M. Multi lens elements of an eyepiece are all coated to avoid such internal reflections. In the early days it would have been a problem,yes. Q: You said looking at the cillia and some patients had particular diseases, stopping them beating correctly . Do patients actually gret their cells checked , via your unit , to find what the disease is or by others? No thats what we do, we're one of 3 centres in England that does this . A patient would be referred to us if they had chronic lung infections , not clearing their lungs properly , what is breather in gets trapped in . They will come with that clinical history of problems and investigated in a variety of wayd. Noone knows why but the concentration of nitric oxide in the exhaled breathe of someone with PCB is slightly higher than a normal person. So a NO test, also a nose scrape that obtains cells for a high speed video. Its the same cillia there as in the lungs? Yes. Its a genetic mutation and will be the same in all such cells. What is the big pattern, even if it looks normal there might be something behind that disease. If showing abnormal then go on to TeM. Unlike something like CF which is a single gene , single base mutation, one amino acid in one protein affected. With PCB can be hundreds of mutations in hundreds of genes, contributing to that ciliary structure , any one of which could go wrong. It might not be a protein in the scilia , but a protein error in the assembly process. This multiplicity is why its called a syndrome rather than a disease. The incidence is about 1 in 20,000 of the population . CF is a killer in terms of short life span PCD is a cronic debilitator and allied problems like the female reproductive system involves scillia, interation with sperm. In males the sperm cannot swim because the flagella ... . When you are an early embryo there is 1 scillia , the primary scillia that beats and sets up a fluid circulation , in a hollow spherical housing, and that single cell beating is enough to cause the body to twist to give the asymetry of our bodies. With scillia failure there, the body will go 50% that way or the other. Half the people with PCD have sinus ?, where half they're body is the other way round, just by randomness. Thats not life changing, but from the communities we have most of our referals from, is first cousin marriages and this becomes more common. The bad genes tend to stick around and get amplified, and the incidence in such communities can be more like 1 in 200, similar with island communities. Q: What would be the cost of the nose sampling procedure? We don't cost it like that. Because of all the rare diseases , the NHS has a specific budget , that funds certain units. So its not patient by patient funding. TeM is not a fast process . At the clinics are consulatants , specialist nurse to do the brushing. High speed vdeo takes a couple of hours to set up and do, the TeM can take several days or weeks , but not continuous as stepped. But presumably several thousand pounds. Other than physiotherapy to clear the lungs there is not much that can be done. One day there wil lbe better treatments, but I doubt it will be gene therapy, as its an inconvenience rather than a killer so not a priority. Q: In the video of scillia , there seemed to be a local group synchronised in their beating in a wave motion, what is the mechanism that causes the synchronising? We don't understand it. The entire lung system is syncronised , because if one scillia wanted to push something up and the next one down , it would get nowhere. The entire lot is syncronised together . Is it related to heart-muscle in that an isolated heart muscle will beat .? The lung scilia twitch with a mexican wave, effector stroke and a recovery. There must be some sort of mechanical connectio nas the cells are glued together. In the heart you have the pacemaker cells a group of neurons that work together and send a pulse out on a regular basis. A manmade external pacemaker is just taking over that natural function. For scillia there must be some sort of mechanical feedback between cells. If you held these cells horizontal does that function still work? They are tiny, perhaps 2 microns, cannot be related to gravity as when you lay on your side , they still work, pushing outward of the airway now horizontally rather than vertically. Q: ??? The first thing we do with a patient is make sure they blow their nose really well as the last thing you want with a sample is the cells to stick together with muccus. Another process with lung conditions is a bronchial lavage? a fluid into the lung and wash the lung out and lok at that. Bacterial cultures and counts on that etc , looking for anything unusual ,if nothing odd found, then they come to us. 28/80/59 B 40 95min W86 pint W87-94 air Q W96 july 17 W97 basingstoke S17-19 bob

[ An expanded version of her talk , that won through 8 doctoral research challengers per faculty and 8 faculties of Southampton University, so 64 challengers all together, in their 2018 Three Minute Thesis competition. ] Tuesday 03 July 2018, Rachel Owen, Soton Uni: Using the cellular origins of two contagious cancers to identify vaccine targets. The Tasmanian Devil, an endangered carnivorous marsupial which exists in the wild only on the island of Tasmania, is under threat by the emergence of two independent cancers, Devil Facial Tumour (DFT) 1 and 2. Both of these cancers possess the remarkable ability to transmit between animals, and have quickly spread across most of the island. By using the cellular origins of these cancers as a guide, I am aiming to identify cellular targets in both cancers which could be used to develop vaccines against them, stopping the spread of the disease and protecting an already vulnerable species from extinction. Cancer is a group of diseases caused by uncontrolled cell division . A healthy cell aquires a mutation and it become3s cancerous. This cance cell continues to divide uncontrollably , potentially forever, and thats how a tumour forms. For a tumour to form and survive it must overcome a lot of cellular defences. Like the immune system , constantly fighting the growth of tumours, mechanisms in place to control the cell-cycle, mechanisms t stop the growth of cells and mechanisms that replace cell death. Hence the hallmarks of cancer, a set of things that cancers need to be able to do , to form,grow and survive. Mainly avoiding the immune system, sustan ing qualitive? signalling , avoid growth suppression , avoid cell death, bu tthe one I'll be focussing on is that they have to evade the immune system. So contagious cancers, usually people have not heard of. So how does a C become contagious . A few things need to be in place initially. The cells have to have a physical route to be able to transmit between 2 different individuals. The cells that do transmit have to be able to invade tissue , to divide, and grow like aC would. They have to evade the immune system and specifically the anti-tumour response of the IS. They have to evade the anti-graft response, which most Cs don't come up against. At least 8 instances in nature where Cs have gained the ability to contagious. One is canine venereal transmission tumour , a sexually transmitted tumour that circulates in dogs ,wolves and foxes , hyenas. Its widespread, across most of the world. THe Uk is one of the few places that doesn't have this C. Mainly associated with coutries with lots of stray dogs or where they let pet dogs run around free. Generally this tumour is not fatal. It spreads and grows fast but reaches a point where the tumour stops growing and often it disappears, the dog is fine and rarely needs treatment. First identified late 1800s , but thought to be about 10,000 years old. Probably emerged in a wolf or an ancient dog breed. The are 5 of these Cs circulating in marine bi-valves. Muscles, clams and cockles, described over hte last 3 years and realising they are contagious. We know these Cs have been around a lot longer, only recently is start to understand them. One of them has crosed the barrier between species. Formed in one species but now only exists in a different species, so has managed to avoid the IS. As we have 5 types in clams , it suggests these sorts of tumour may be quite common in the marine environment. There are no truely transmissible Cs in humans, we don't tend to have the routes of transmission they need and our IS is pretty good. But there are rare instances where Cs to transmit between peole. 1 is during organ transplant , donor to recipient, rare and usually because the recipient is on immuno-supressants. Another is mother to foetus during pregnancy, even rarer. The foetus has a dgree of immune priviledge to stop the mother's body rejecting it as foreign. So only when the IS is dampened in some way. The tape-worm that turns into a tumour. A man in Colombia with late stage AIDS, soa bad IS at that point. He had lots of stange nodules in his lungs , not lnowing what they were. When he died , he had a massive tapeworm in his gut, that had developed a C and the nodules in his lungs were Cs from the tapeworm. Leaving the ones I'll talk about Tasmanuan Devil Facial Tumours , 2 different T that circulate i nthe TD, TDFTa and 2 , both causing necrotic rotten Ts around the face and mouth that kill the TDs most of the time, high mortality rate. The only mammal we know about that harbours 2 different contagious Cs. TDs are the worlds largest carniverous marsupial. Endemic to the Oz island of Tasmania. They went extent on the mainland about 400 years ago, after humans settled and killed them off. Like all marsupials they have a pouch, give birth to very undeveloped joeys, so first few months it lives in the pouch. When fully developed they become independent quite quickly. They are generally solitary and nocturnal. So how did such a cute looking animal get the name TD. A video explaining the reason, unearthly yelps and growls and snuffling , wrestling between a pair over a carcas. The first setllers only ever heard them as nocturnal , not saw them , and hearing that sort of noise out of the darkness of night , you'd think demonic. The feeding frenzies when they come across a carcas involve a lot of fighting , snapping at each other, biting each other. They have one of the strongest bites in the animal kingdom relative to size. They damage each others faces a lot during these frenzies. They were historically persecuted by farmers , who thought they were hunting their livestock. Their populatin was decimated a few times . In reality they don't hunt often , going for roadkill , primarily scavangers. Farmers now realise they are beneficial as they clear up a lot of dead animals, stopping infection spreading to their animals. There has been lots of TDs on Tansmania for a long time, sometimes they were killed but their numbers came back. Since 1996 the populations have been in steep decline. Oerall 60% drop in TDs, in some parts of the island its > 90%. In 2008 they were reclassified to endangered. This later decline is very much due to the emergence of the TDFTs and particular the FT1. Looking a tthe number of sightings in a 10km area and by years, plot showing when FT1 first emerged and numbers dropping steadily. We're not sure how these FTs emerged. No evidence of any external causes, not caused by UV or external pollutants etc. The fact they've been historically persecuted and recovered a few times has reduced the genetic diversity in the species, reducing species health and being prone to diseases , is a risk factor. They bite each other so often is also a risk factor for transmissible Cs like this, but we don't know a specific reason for FT appearance. FT1 was first identified in NE Tasmania i 1996 but unsure how nuch earlier it arose. Nowadys it exists over most of the island. they recntly found a population in the SW that is currently disease free and they will do some genetics on them to see if there is a reason for that, or its just not reached then yet. FT1 emerged in the Schwarm ? cells, in the peripheral nervous system, not in the brain , but in other nerves of the body. They wrap around the nerve axons , forming the myalin sheath, a fatty layer that speeds up nerve conduction. Only 2 types of cell produce this myalin sheath , 1 is the Schwarm cell and the other is the equivalent in the brain the eli?cyte. A specific protein periaxin ? in Schwarm cells is a marker for TDF1, which was the first evidence of where the FT1 came from. The FT2 emerged in 2014 in south Tasmania and cannot find evidence of it existing any earlier than that. It may have emerged only 4 or 5 years ago, and is currently yet to leave that region. Only been officually documented in 11 TDs but about 10% disease prevalence in that region. And we dn't know where the FT2 came from at the moment. Despite the Ts looking the same, they are different. They evolved independently. Slices of T tissue and darker purple dots are the T cells. The FT1 the T cells are in nests or bundles ,same in all FT1s but FT2 doesn't , a completely different architecture. Periactin? the marker for DFT1 , the DF2 is completely negative for that. The brown stain is Periactin positive but none for the DF2 tumour. The 2 brown stains at the bootom are Schwarm cells where there is periactin and so staining there, The T itself is negative. The chromosomes we see in a normal male TD, FT1 and Ft2 , FT1 has 4 marker chromosomes which we see in all DFT1 Ts and we never see in healthy tissue. That is caused by the C. DFT2 has a Y chromosome , so its emerged in a male TD. We cant find any evidence of a Y chromosome in DFT1 so it looks as though its emerged in a female TD. 2 different origins, emerged separately, they are separate Ts, despite looking the same and spread the same way. C is not normally a contagious disease. Our IS can recognise and remove foreign cells. So 2 mice that are different, try a skin graft from one to the other , there is rapid graft rejection, because of the IS of the recipient mouse, recognises it and kills it. This is called MHC class 1? , which is a sort of cellular barcode, consisting of 3 lelements a heavy chain which is very variable within a species , a small accessory protein Beta2M ?, and a peptide. A peptide is just a short fragment of protein , 8 to 12 amino acids long, and is generated as proteins in a cell ar ebroken down and reformed. Normal protein turnover, some of them get put on the cell surface. This complex forms together, sits on the cell surface and acts as a buffer to the IS , giving a snapshot of how healthy the cell is. The IS can scan those molecules , look at the heavy chain and the peptides and if either is foreign , it will destroy the cell. The situation where we have 2 genetically different mice , whats most likely to be fdifferent is the heavy chain , the IS rapidly recognises trhat and get rapid graft rejection. The IS can also recognose the [eptide , so2 mice genetically diiferent but both with the same MHC class1 heavy-chain , but hte peptie is different ,the IS will still recognise this and reject the graft. But doing it much slower. Surviable grafts , without immune suppression is if they are genetically identical. So MHC class1 is the same and peptide bound to it is the same. So why don't TDs reject FT1. They have a functional IS and from experiments we know thry will reject skin grafts quickly. These contagious Cs are essentially cellular grafts and should be rejected, but we don't know why. Itts been found recently that FT1 doesn't express MHC class1 on its cell surface, so to hide from the IS, its just got rid of the barcode, nothing for the IS to scan and find as foreign. TF2 does express it , so we don't yet know how it evades immunity detection. The fact that FT1 is removing it and that TDs can reject skin grafts , makes us want to see if there is a way to exploit this system , that TDs can recognise foreign cells to see if it can start recognising TDFTs . Our lab is working on how to reduce FT spread and working on something called a peptide vaccine. We are in Southampton, not Tasmania , so how do we get samples. We predominatelty work in cell-lines. Get a T and cells growing in it , smash up the T and isolate some of the cells. Plsce in a media that is just sugar and nutrients and things the cells need, in a flask, the cells will stick to the bottom and grow. We get them sent once and then we can grow as many as we want. We grow them up, freeze them down, grow them up again. We can get thousands or billions of them and can do what we like with them, essentially a limitless source of biological material. There ar elimitations, this is not how Ts grow in the wild, so there is debate on how well these cells reflect what the wild C looks like and acts like. So on top of this we also use fixed T samples. So from a biopsy from a wild TD , fix it so everything stays in the same place , embed it in wax, cut and slice or smash it up and look at the genes expressed. No one keeps TDs in a lab , they're an endangered species. So derived from wild TDs, so a need to catch them first. They are nocturnal and shy so difficult and we often can't catch the same TD twice, so statistical significance when working on wild TDs is a real problem. Hence we tend to stick to dell lines. We have collaborators in Tasmania and perform regular trapping trips. Taking white bucket like things out to sites where TDs are known to be , return in the morning and see if any TDs in there. So visual assesment for any signs of a T around the face , if they do then take a biopsy. If the T is really bad then the T is euthanised if its quality of life wil lbe affected. Most of them are released . So we have 2 contagious Cs emerging in 1 species in just over 20 years. That suggests a risk of maybe developing mor eof these. The fact they have such a reduced genetic diversity means the species health is not too good. So if another C emerges then it will cause more damage to the TDs that are left. It is urgent we find ways to help them. So work on breeding and re-release, on one of the small islands skirting Tasmania has been populated with healthy TDs with genetically diverse breeding. The Morura? Island genetic diversity project. Also zoos breeding them in captivity and re-releasing. And biologists are trying to work to some sort of vaccine. So what is MHC class1 doing. FT1 does express MHCclss1 , flow-cytometry and cell count on the Y axis and expression on the x-axis , dotted line negative H2M and pink line is stained H2M , negatve not expressing MHC class1. FT2 is expressing on the surface , shown in our lab by another PhD student last year. Treat them with an inflammatory cytokine , interferon gamma , inflates the cell going into an immune response, we see an upregulation of MHC class1. So inflame the cell and they will express MHCclass1. Even though FT2 already expresses MHC class1 , I've recently shown it also upregulates MHC class1 if treated with an inflammatory cytokine. 3 different DFT2 cell lines, DF2 regulates up to MHC class 1 significantly more than DFT1 does . So can we vaccinate against DFTs . A small number of wild TDs, trapped and tested that show an immune response to FT1 , this is correlated with ?ion of the Ts and some TDs survive for 3 years with no evidence of the disease reurning. This is good news, these TDs in their blood antibodies against MHC class1 + DFT1, so the MHC class 1, on the TDF1 cells is eliciting an imune response and if you take those MHCclass1+ cells , you can vacinate against the DFT1. Some success in doing this , but currently a bit limited and the responses a bit limited. So we want to refine this or thier peptides to vacinate against TDFts. MHCclass1 is definirely involved i nthe immune repsonse to TDFT1 and its presence on TDFT1 means the TDs immune system can clear out the cells a lot better. The fact it upregulates TDF2, makes it relevant to FT2 n as well. A peptide vacine would be feasible. It has been extensively explored for human C but is very complicated. The basics of it is; you have a healthy cell , its expressing a normal peptide on the cell surface , the IS is not bothered it doesn't flag up anything. When it becomes a C, ther's a mutation which messes up a lot of the proteins in the cell . If just one of these proteins to be expressing a peptide on MHCclass1 suddenly we have a new peptide on the cell suface, that is potentially foreign to the IS. If we can use that as a vaccine target , maybe we can ellicit an immune repsonse that only affects the cancer cell. In theory this is T specific and there should be no adverse side-effects, hence its use in C treatment. So an attractive option biut they're difficult. A study compared a healthy mouse genes with a cat-mouse C gene and they found despite many thousands of mutations in the DNA, very few become T specific, the antigens. Very few are on MHC class 1 and even fewer have any response from the IS. Even if you get to that point, you can have similar peptides on other cells that will cause a response . Hence target effects that can be fatal in some trials, so a difficult area to work in. So we start , we really need understand what the peptides see on these Cs. So how to find these mutated peptides. In single organism C its relatively easy, the organism forms the C, so go back to the organism that formed it, isolate the cell type the C mutated from , its healthy #cell-type of i=origin and make a direct comparison . Comparing all the peptides and can see which one is defective. Its a bit fifferent with TDs, so 2 TDs which have both undergone mutagenic events to form DFT1 and DFT2 , both TDs are #dead. Either died because of the disease or because old, they don't live long . We cant make direct comparisons, w ehave to do instead is look at the current healthy TD popultion , isolate the healthy cell-type of origin , pool all that together and then compare to the Cs. Trying to identify specific mutations. We can do this for TDFT1 because we know it came from a Schwarm cell , but we don't know where TDFT2 came from yet. This is a huge part of my project, what cell type did the FT2 originate. The top 20 proteins that ar eover-expressed in FT2 compared to fibroblasts that are a healthy control and TF1. Every protein in red is a protein with a direct function in the nervous system . Evry protein in blue is a protein we see over-expressed i nthe nervous system . The TF2 is enriched compared to the fibroblasts yet it over-expresses loss of proteins from the nervous system, so it looks like a nervous system protein . Now looking at the gene expression , RTDSTRs ? a way of looking at genes expressed in cells. The control should not change between cell lines. All these are myalin associated genes which we should be seeing in only 2 cell-types and we are seening them in all the DFT ? , at alower level in FT1 but they are there. Which means DF2 has come from a cell-line that produces myalin. When you stain the FT2 sections for Schwarm cell markers NB and S100 and ciatic nerve as a positive control which is highly enriched for Schwarm cells, can see if there is brown staining on FT1 and FT2. So DFT2 Ts are positive to schwarm cell markers. My conclusion is that TF2 has emerged in a similar cellline as as TF1 , it produces myalin from a myalin producing cell-type which brings it down to either of 2 cells ,Schwarm cell or Eligodentacyte? We think it originated in a more immature cell version of this, than DTF1 did. It suggests TD myalinating cells are predisposed to contagious Cs , so it highlights how important how are vaccine strategies are. We have 2 independent Cs , both emerged from similar sell-types, we know if we treat these Cs with interferon-gamma we can upregulate the amount of MHC class1 on the cell-surface. This means we are putting more peptides on the cell surface , which the IS could notice are foreign. Most of these peptides would be differnet beteen the 2 Cs. But what if we can find 2 peptides which are both mutated in the same way , so a peptide on both Cs which we don't find anywhere else in the body. If we can find that peptide , then a single vaccine is possible to help attack both Cs. This iswhat our lab is going for. So currently I'm looking at what peptides of MHC class 1 are actually binding in Ft1 and Ft2 , are any of these peptides mutated in eithe rFt1 or Ft2 and are any of these peptides , that are mutated, are actually present on both Cs. If we can find those, then thats a foundation for a vaccine, that could help Tds survive both these unusual and agressive Cs. Thanks to our lab coleagues, our collaborators at Monash and Melborne . Q: When you've got the IS to recognize a foreign peptide and it attacks those cells , how successful is it in attacking enough cells to make the recipient healthy or not healthy. We don't really know yet. There are a lot of factors involved. Some peptides just don't ellicit much immune reponse, and it depends on a lot of things. Again a factor full of complicated things in the generation of vaccines. Sometimes you find peptides that are unique, nowhere else in the body , and for some reason the IS will not recognise them. Or it will and the reponse is muted. Others have a huge response to a peptide, so completely varied . If we find a peptide that is really immunogenic then theoretically you wouldn't need that nmuch to get the IS reallg going. But more likely not going to be strongly immunogenic, which is probably how they're spreading. It would be a case of using adjuvants ? and things that enhance the immune response ot the vaccine in the first place. Q: So you don't have enough knowledge as to why some peptides don't bring abou tthe response and others do. Sometimes it seems a bit random. Certain amino acids, the ones with big side chains and rings in them essentiallly they tend to have a bigger immune reponse, why i'm not sure and noone else either. Bigger bulkier peptides tend to activate the IS more than small peptides. But no guarantee of finding the big ones, as presumably those wil lbe the first targets for the Cs to get rid of. Q: ? T-cells ? if you could isolate them from immune cells , then screen those against the peptides ? Q: You don't use radio-tracking to zero-in on repeat samplings of the same animal in the wild? They've just started doing that. There is a problem with the shape of their necks , squat necks and easy for the trackers to fall off. They don't really have a neck. Q: Any TDs at Marwell or any UK zoological sites ? I don't think so. Thats not many outside of Oz. San Diego and Denmark has some. Q: How did these problems emerge? I can understand the Island Effect on genetics . Is there othe rhuman involvement beyond trying to eradicate them, I'm thinking pollution ? A lab we work with in Cambridge has looke dfor it , for specific signatures in the genome for something common from UV damage etc. The most common signature for these Cs is its age-related. It appears in quite young TDs. Its seems to be appearing from a natural source rathr than something external. Q: It all seems such a strange situation, I'd have thought it was fundamental to nail down the origins. Could be viral possibility. It certainly doesn't ? spread ? but that doesn't mean original transformation was not due to a virus. The original transmission could have been by a virus and traces of those viruses are now lost. Especially now showing that the Cs are similar cell-types , then that makes more sense ??? Q: Being marsupials , does that mean they could be exposed to more exotic illnesses. No other marsupials have anything like this . Al lvery strange. It probably comes down to TDs are unique and has a very easy method of transmission , they fight so regularly as part of their behaviour. Maybe these sorts of Cs are forming oin lots of species but because they don't interact in the same way, we don't see it spread. Form and then die in that one animal. Its got to the face because they bite one another. Q: so there can be a feedback mechanism to assist how these Cs can evade IS processes. If a C forms in a body, that body dies, with no transfer to another host , then its purely down to random generation. With a feedback process it could accelerate an otherwise random event? In the human C process a C can metasticise to anothe rorgan , the C starts in one place and then move . Those cells then have to overcome new immune challenges in the new environment. That in a way is similar to these Cs , instead of going to a new organ they go to a new individual. But can that speed up the evolution of these sorts of C. Q: For the marine animals with these sorts of Cs , that is just co-evolution , just isolted random events with no cross-over between species? Other than the one that now exists i na different species, I think they all emerged separtely. They seem to have different mechanisms as to how they have become transmissable and formed in different ways. It looks as though the emergence of contagious Cs , at least in the sea might be quite common. The bivalves off the USA were dying off , but no one realised it was due to Cs. Q: Were they geographically isolated or around the world? When fisrst noticed off N America , they thought it was geographically isolated , now its found in the Med off Spain . Q: the proposed TD vaccine only protects individual animals , doesn't protect any offspring and so a massive vaccination procedure required? Yes. It would e a combination of capturing what you could. Plus the captive ones on the outer islands , were all vaccinated on relaease, it would take a while, but eventually there would be herd immunity, the point where the Cs can't spread any more. If we gat a vaccine, then yes it will be a massive undertaking, a lot of money to get that running. The government of Tasmania is fully interested, some releases in northern Tasmania , been quite wiolling to trial of vaccinating the whole cells, the problem is its really expensive ot do a vaccine that way. Not viable perhaps fo rhte whole population and no way of monitoring the anomals after vacination . We can't do a proper scientific study. Q: THe trick where it doesn't have the code, ??? would that work for humans ? That is common with human cancers , like how they put up a mutated peptide , Cs are aware they do that, that comes in with the immune pressure and happens a lot with human Cs. It correlates with more agressive Cs, they tend to get rid of MHC class1 on their cell surface, they just stop expressing it, then they re really hard to treat. There is a lot of effort for humn Cs , honing up that ?? , in the past when people have tried making the inflammatory cytokines that we are working with , it can cause terrible immune reactions, called a cytokine storm in patients, the IS goes into overdrive and the patient dies. So its not seen as a viable treatment for humans unfortunately. Finding other ways of manipulating C cells so they upregulate MHC class1 , is something people are looking in to. Unkowing the geography of Tasmania , is there mountain ranges and rivers that can isolate communities , so you can re-release knowing it is very unlikely to be cross-connect with other communities, as I assume they are otherwise free to roam? The main one we know of is in central Tasmania . The is a mountain range thru the middle . It was thought at one time that as the disease spread east to west, that that range would stop FT1 but it keeps spreading. Birds or something could be a vector for transfer? No reason it couldn't be , I think they assume the TDs have simply got up there. We don't even know how long the cells can live outside of the TDs and active cuts or sores. Presumably they could live a bit like a virus ???. I was thinking of concerns over here of culls to supress badgers , because of bovine TB , but a theory goes, kill them off in one area and then others from outside move in with TB and then back to square1 ? Human manipul;tion does not always work. How do they ensure non-disturbance of existing populations, via re=releases? I don't think thye worry too much , they just want more TDs back on the island. That badger type UK research I don't think has been done for the TD situation. How many in the wild in Tasmania at the moment? About 20 to 30,000 , it was 120-150,000 . The last surviving one on mainland Oz was when? There is aa bit of debate on when the extinction but consensus is about 400 years ago, shortly after European settlers. Have they ever become pets? I don't think so . Apparently they are very nice natured until about age 2 and sexual maturity and they become a nightmare. A young TD you could go up to and pet, nice and placid. With animal rescue centres that deal with TDs, the people handle the babies , ut stay clear of the 2year olds or older as the only way they interact is agressively. They also smell terrible as well. If they do attack a human they can do a l;ot of damage. For Oz generally although very large, it seems that if anything can go wrong with human interactions with fauna, it does go wrong. I'm thinking of the mice, the rabits , the cane-toads, it just does not seem to happen elsewhere? Is that situation even worse in smaller Tasmania? THere always is a problem with island populations becuae they generate very specific eco-systems , that becomes very finely tuned , a delicate balance . When there is nothing that can come in and balannce it out, limited to what is already there on the island. The second you bring something in it can all go out of kilter, no way for the eco-syetem to fight back. For example compare to Europe, it doesn;t happen on such an intense scale , there is natural stuff that can come back in and refil gaps. If you accidentally wipe out sonmething on Tasmania , there is nothing to fill in. Its isolted from everywhere . Oz gets it becuase it sa very ig island. Things get wiped here quickly ,by small changes i nthe environment . Even in the UK the red squirrel can only survive on outlier islands of the UK, in the south of the country. So that is a precaripus situation if anything gets on to Brownsea Island, just one grey squirrel and that population of reds would be gone. So climate and genetics can affect the island effect? In more ways than you may intially expect, on an island, over a long time the genetics effect and then nothing else that come in and replace. One thing goes and then the entire island has to change. Or one thing comes in and all change. All highly responsive to outside interference. hat made you want to do TD for your PhD? I was always interested in C as a biologist/chemist at uni, but I wanted to be avet when a lot younger, but decided I didn't like the people side of that. I put the ides of animals out of my mind and went down the C route, then this topic turned up as research , involving both endangered species and C at the same time. So a perfect role for me. You apply at PhD level to a specific project and this was the perfect fit for me. It does seem a bit odd, yourself and a lab on the other side o fthe world heavily involved in this research? And another lab in Cambridge in the UK and a lab in the USA. Is that fairly common, not just TDs , that structure of worlwide spread? I think it comes from people who have an underlying interest in a biological process and they end up studying a sole gene or disease that allows them to study a molecule . The Canbridge group emerged from tumour evolution , using the TD ones as a model. We have an objective of something very practical from our research , but along the way explore the underlying mechanisms ???. In the USA they're modelling the spread and the factors that influence it. Its a combination of people seeing a real issue of the moment, a problem they can address , and a scientific interest in something a bit more broad. I suppose 20 or 30 years ago you could not have done this trans-national research , withput the principle of cell-line culture, requiring people to physically going to the relevant country? Yes, the cell-line stuff is so integral. For these cell-lines, if you came back 50 years time , it would still be the same cell-line? If you keep freezing them , when you're not aactually growing them , then they will keep reasonably stable. But they do change. The most famous cell-line is the Heeler-cell ? a cervical C cell line from an Afro-Caribbean woman in the USA. But look at those cells these days , there is an obscene ampunt of chromosomes that have appeared from nowhere. They don't have half the organelles that you expect to see in a cell. Its come to the point where some people are questioning if these really are cells any more. There are limitations . You bring them up from frozen, grow them on a plate , but when they fil lthe plate you have to subdivide onto more plates for growing more. ut there is only a certain number of times you can do that , and you start to see the cells changing. All cell-lines not jus tthe Healer-cells. eg DF2 which normally spread out and look like stars , lots of sticking out projections but the longer you grow them, those projections get shorter , start growing strangely , stick to each other , all sorts of weird things when they are farther down the propogation line. So even without looking at the genes or the proteins or whatever you can simply see the cells start to look different after too many divisions. Thats why we have multiple cell-lines , isolated from different TDs and different tumours at different times. The idea is that if they are stil lreflecting each other , they can stil lreflect the tumour samples , and so still a good enough modelfor our use. ut you have to be careful as a lot of limitations with cell-line work.

Tuesday 17 July 2018 Jonathan Ridley, Head of Engineering ,Maritime Science and Engineering, Solent University : Hydrofoil design and use (second talk, previous talk on yacht design) An example of one of our one-time students Jason Kerr graduated 1994. The pinnacle of yacht design is the Admirals Cup and the last one had 3 teams with some of our graduates working for them. By the third year their doing 3D CAD work designing vessels from scratch , structural design and theory , power, systems, aerodynamics, everything. A hydrofoil we built in 2014 called Solent Whisper and this is where our interest in small craft hydrofoils (H) took off. A history of hydroils. Our hero is Sir George Hayley. A scientist who made astounding contributions to sci and eng, but we've almost forgotten about him. He re-invented the wheel, the tension spoke-wheel, with little knowledge of ship-stability he invented self-righting lifeboats, he invented tracked vehicles calling them universal railway. Before internal combustion engines came along he invented an internal combustion engine that ran on gunpowder, invented automatic railway crossings, also the seabelt. He started to lok at aerodynamics . Late 1700s /early 1800s anyone who wanted to fly simulated birds and flapping wings, fundamentally flawed for humans. George Hayley observed birds and started to derrive a theory of fligth. 1809/1810 he published his scientific paper on aerial navigation. His gunpowder engine would have worked better with a gaseous fuel. It was the same with powered flight , but no engine light enough and powerful enough, but if we did, then this is what we could do. He was the first to look at an aerofoil shape, at lift ,drag , thrust and weight and would have to be balanced together to make it work . He didn't have a wind tunnel he created a long rotating arm, a foil on one end and a counterbalance on the other end and a motor to rotate it. Measuring the rotating force, and the lift, simple experiments but he learnt a lot. He learnt about the control of foils moving thru the air and how to control lift. He came up with heavier than air principles and understood and derived the centr of lift and the centre of pressure, how forces move and where they move. He looked at camber effects of different shapes and different lift andhow to control it and in 1848 he had something we'd recognise today as an aircraft, with a set of wings , tailplane and rudder for control , the world's first gliderr. He got a local boy to fly it , as fairly light , and launched him off a hill. 1853 he has the second successful glider , using his coachman this time to fly it. One longish flight and landed and the coachman would not repeat it. The functional knowledge of foils is essential for aircraft and essential for Hs. All goes quite but Henrico Fullerini ? starts to look at Hs. In 1911 he achieved 42.5mph on water with just 60hp of engine, He did a lot of background work and published a lot about H, from an experimental point of view. 1889 to 1901 John Thornycroft on the Thames ???. 1905 William Beecham did deep scientific analysis of Hs. In 1919 Alexander graham Bell had a go, the HD4 hydrofoil with 700hp he achieved 71mph on water. That would be pretty impressive even today. The fastes object on the planet in 1919 was the Sopwith Dragon aircraft that would do 150mph. Developent on from then comes from the aircraft industry. They have sea planes that need to take off from water, water is sticky stuff and difficult to go fast enough, put some hydrofoils under such planes and get some lift then can get more air speed. Not particularly successful as going faster creates more drag , your aircraft becomes less efficient. In 1954 the next big step in hydrofoils. Frank and Stella Hemingley , Frank is a naval officer who survived WW2 and he wanted to set the world water-speed record. While in USA he marries his wife Stella , a pair keen on breaking the speed record. They built a hydrofoil they called the White Hawk . All Hemmingly had was a drawing of what they thought their hydrofoil should look like. They needed someone with more technical knowlege and enquired of Imperial College as to whether they had a student who could do stress calculations for us and design the vessel. They lent them a Ken Norris , went to their house in Chelsea , and with no proper plans , had to start from scratch. It looks a bit like Bluebird , because Ken Norris went on to design Bluebird. His brother was also an experienced engineer , Lou Norris who worked for Sir John Chobham, trying to get the world water speed record in similar time. Ken Norris designed the fatal for Cambell K7 Bluebird , over 300mph . Ken Norris also designed the car the CM7 , stands for Cambell Morris. He then went on to work on Thrust2 and then ???. Somehow with his connections ot the Navy , Frank gets hold of a Whitley turbo-jet, 1943. They go as fast as they can down Lake Windermere, a few runs , getting faster and faster, without any timed runs, just to see how well the vessel works. They get up to a certain speed , then a bit faster and it nose-dives and sinks. A jet engine running at full speed, suddenly immersed in water , is a no-no. They managed to get Rolls Royce to lend them 2 Derwent? jet engines and the technicians to run them. They return ot the Lake District, see how fast they can go and the same thing happens, at a certain speed, it nose-dives. The 1950s its a tandem cockpit and both are in there. Frank did the running and testing but it was alwys his intention, when they broke the world speed record that Stella would be driving. As not a formal record attempt , it was not recorded. A pitot-static tube , measuring their speed didn't work. Frank reckoned they were doing over 100mph , but from the physics and difficulty in judging speed while on water, that speed was unlikely. They spend winter in Windermere , working on the boat, waiting for a break in the weather. The break never comes and the Americans get interested in rreally fast Hs. They go over to the states and the US Navy gets interested, and the technical points are discussed. On the technical front Frank and Stella were happy, the US Navy was happy but contracts had to be arranged. After several years of lawyering Stella does a few demo runs and the US navy decides it was outdated and no longer interested. As a ps to this vessel , Frank brought the vesel back to the UK, bringing it through Southampton Docks. HM Revenue and Customs turned up , saying Frank owed them money, and thought it was an import and impounded it. Nobody knows where that boat ended up , it did not leave Southampton. Perhaps in the corner of an old warehouse somewhere in the docks , it may still lie. They had 4,000 pounds force of engine , delivering 17.8KN of thrust . Go back to Alexander bell 700HP and got 71mph. This time with all that thrust they got 70.6mph. Al lthat developement and time and just short of the previous record. Then a few commercial Hs , the Boeing Jet-Foil , they still operate in Hong Kong harbour etc. Fairly successful, roughly the same passenger payload asa 737 and much the same cost. Still operated today . There was a lot of military investigation into Hs as to performance and speed . They did lots of trials but did not get very far . One problem for the military is the generatio nof huge amounts of spray behind them, the spray is very cold , so not stealthy along with the noise. Also hit any debris in th e water and Hs are relitively delicate. They run between Rhodes and Greece and Tukey , on the larger rivers of East Europe and russia . So why have Hs not become bigger and faster over time. Datapoints of commercial and successful Hs , horizontally the power to weight ratio versus the top speed. If not a lot of power or a lot of power, and you can get to 70mph , and you basically hit a brick wall. With Hs there is a top-speed that cannot be exceeded. 1950s and 1960s , the Hs themselves were made of aluminium , ? with steel, moving very quickly thru water . Hit something submerged and they are easily damaged , then back to the shipyard for a very expensive refit. The quote is Hs are very nice until you slice a dolphin in half. It all went quiet in the early 1970s . Then the sailing world got interested in the International Moths?, the closest sailing gets to a blood-sport. They are lethal, the rules for Moths were they have to be within a certain set of dimensions and since 1970s carbon-fibre just about comes into the cost-range of people into these sorts of craft. We start to see there developement, going faster and faster . Moth sailors realised quickly that if you wanted to really hurt yourself , then get above the water and you can fall off at greater speed than ever. From 1974 a lot of individual trials and experimenting, empiricalwork but not university reasearch. Going round Portland harbour as fast as possible. Even today , the Moth class is a pinnacle of sailing in terms of small craft performance weight and speed and technology. 1980s/1990s,to 2000 the Americas Cup , by 2003 was using the IOCC 72 ? a very graceful monohull , but from an audience perspective , 2 of them racing far off, pretty boring. They developed new rules and looked at multi-hulls, catamarans, trimarans. The team to beat recently has been Team New Zealand, the world leaders in this sort of tech. For the 2013 America's Cup, everyomne agreed on big cats. The Kiwis launched their boat and the spies were out for the trials. It was sailing but extremely slow. Second day out and everyone else was really pleased at how slow it was. Daggerboards. As you are sailing the wind is trying to push you sideways as well as forwards. So to stop that you have some vertical board underwater , the daggerboard. the Kiwis found a little loophole in the rules, it did not say what you could do or not do with daggerboards, just that they were allowed. They bent the tips of the dagerboards in , and on day 3 of the trials in Aukland harbour and the boat shot off into the distance. Mass panic and a huge amount of plagurism everyone tried to quickly ament their daggerboards. This was the start of really big boats going faster. Far better hydrodynamics and far better materials allowing to build such large structures. Unfortunately they were inherently dangerous. In one of the races a UK sailor was killed on one of these vessels. The organisers decided for the next cup to throttle things back a bit. The next race, still cats going as fast as possible but a bit slower. The speed record was just over 40mph ,fast enough. For the next cup coming up AC36 in 2021 , a whole new type of H , the foils cant or rotate in or out of the water as required and the vessel can sail along balanced on 2 foils. Mathematically its possible, it will be interesting to see in practise. A designer involved with this say they look as though they should crawl up a beach, lay an egg and return to the sea. They all work by lifting the vessel bodily out of thw e water. Another area is where we use Hs not to lift the vessel but to control the flow of water around a vesel. In 2016 the Vendee Globe race , non-stop single-handed around the world and 60 day circumnavigation was possible. So a H on each side, they extend out once its at sea. They produce a lifting force to roll the vessel upright allowing to sail much faster. Video of Schetana ? designed by one of our graduates who graduated in 1993 an Open-60? class. Horrible weather conditions, but the H keeping the vessel upright . How fast its going, the Hs in extended mode . Doing about 25 kn, in those sort of waves, quite fast enough. When it was racing in the southern ocean just south of NZ it hit some debris in hte water , severely damaged hull and limped back into NZ, all on board safe and well bu tthat was the end of the round-the-world race. We are starting to see Hs fitted to very low speed vessels. You don't necessarily want to lift the whole vessel out of the water. But a fairly small foil just lifting the stern slightly can present a better underwater shape and can reduce drag. Not a huge saving perhaps 1 to 3% but for a vessel in almost continous operation , that saving can be significant. I'm involved with a PhD study of Hs on pilot boats for the Port of Southampton, burning 1 million litres of diesel a year. Another project, our towing tank , a higher speed vessel with a bolted on 3D printed H , testing the effect. Assume our interest is to lift a vessel out of the water and to go as fast as possible. An America's Cup boat , sailing along with sails providing the driving force forwards, to go faster a nd faster. Working against that is resistance , water against the hull. Along as our driving force is bigger than the resistance, we accelerate. As we get bigger, the resistance gets bigger , and balanced forces then a steady speed. To go quick we must reduce the resistance as much as possible. The components of resistance, simplified. Air resistance pushing against the vessel, complex as its tied in with the sails , ignore that for the moment. Viscous resitance - water is sticky stuff . Consider a stationary vessel , water flowing past it like a stream . Looking at individual molecules of water , on the surface of the object there is friction with the surface and the molecules slow down. The next layer of molecules above that , a bit of friction with the molecules below , but less , getting less with each layer away from the object. Farther away the molecules can move faster and faster. This is the boundary layer , Newton tells us that force = rate of change of momentum and if we are slowing down these molecules , a change in momentum , must create a force, of drag. Drag force can be significant. Viscous resistance depends on water density, the vessel velocity, the friction coefficient which itself depends on density , the vessel length and the velocity , the dynamic velocity in water , the shape of the object or form-factor but most important is its directly proportional to wetted surface area, the amount of the vessel under water. If I can halve the wetted surface area , I instantly halve the frictional resistance. For an Americas Cup vessel , the wetted surface area . At the maximum draught 40cm of hull underwater and 30 sq m of wetted surface area. If I halve the draught that wetted area drops to 15 sq m. Then wave making resistance. As the vessel moves thru the water , it creates waves, it creates pressure distribution around the vessel under water. But also creates a disturbance at the surface, the Kelvin wave pattern. Waves from the bow , diagonal waves coming off and waves coming off the stern . These wave patterns interact with each other and create drag. Wave making drag depends on water density , vessel speed , wetted surface area , bit also on something called the wave making coefficient which is really complicated. Its difficult to calculate, thats why to solve this problem , we stil lbuild model boats and tow them down a tank of water. Its more accurate and more fun than trying to do the maths for it. WMR depends on speed and the shape of the underwater volume and wetted area. We have some equations to allow us to calculate WMR , the Reynoldsaverage Navier Stokes Equations, non-linear, partial f=differential equations, to be solved simultaneously. Imagine something like 25 million separate variables to get this to work well . If we ganged together the worlds supercomputers and asked them to solve it for us, we would die of old age before the solution. A graph of an AC catamaran, with no foils on. As it goes faster and faste rthe WMR goes up. If I can lift the vessel out of the water , the amount pushing the water and waves out the way reduces , the WM coefficeient goes down , WMD goes down and in theory the vessel can accelerate. Ignoring air resistance. VR is relatively small, WMR is bigger and if we add them up we get the total drag. There is a dip in this curve, caused by waves interacting ewith each other in the WMR at different speeds. We accelerate our vessel, go faster and faster , until so much resistance we reach a fixed maximum spped. For the H version of the AC yacht, stating to generate lift. At about 15mph , 7m/s the lift htey generate, is sufficient to unstick the vessel and start to lift. The problem with Hs is they increase the wetted surface area, counter to what we're trying to avoid. At slower speed we get an increase in the VD but at about 7m/s the lift starts to overcome that, less hull in thr water. As we accelerate furthe rthe VD does not increase too much. The same with the WMD ,not so much an issue as not so dependent on wetted surface area, with the stasrt of lift, reduce the underwater shape and we start to control the drag , and add the 2 plots together. When the H craft is up to about 15m/s or 30knots we're generating about half the drag as the vessel without Hs. Hence instead of limited to 20 knots, we can do 40 knots. A bit of H theory. A theory often banded about is the intelligent fluid theory. H or aerofoil, does not matter, fluid hits the front of it and the fluid splits , some around the top, some around the bottom . We apply a bit of logic to Bernoilli , if we have a shorter path the flow must be going slower and if you slow a fluid down , Bernouilli says the pressure goes up . Along the top, a longer path , so the fluid must go faster , then via carburetor or Bennoilli , the presure must drop. so high pressure under and lower pressure under, must push my foil up. This is the classic theory , taught as an explanation of how a foil works. The reality is different. What goes further must travel faster , but there is nothing to say it must travel faster. Everyone says the top molecule must go faster than the bottom one, so they can meet up again at the same point behind the foil. much research but no one has conclusively proven that water molecules mate for life. With a big foil in a small wind tunnel , because of blockage effects, this van happen. In reality it doesn't work. So start with a flat plate and at slow speed , flat plates make remarkably good aerofoils , the paper aircraft scenario. Take the flow in from the left, hit our flat plate , inclined at some angle of attack , so it will try and create some lift. We will assume there is no viscosity with our fluid , the molecules flow perfectly over one another, an ideal fluid. Plotted here are streamlines , like isobars on a weather chart. they tell us the direction of flow and hte pressure and speed. The closer our streamlines are together , the faster the fluid flows, like isobars and wind on a weather chart. For out foil , the top fluid flows around the top , bottom fluid around the bottom and inbeteeen ther eis a point where our molecules hit the foil and have to decide whether to go up or down. They sit at that point, the stagnation point. At the trailling edge , again a stagnation point . There is a symmetry here in the shape of the streamlines , mirrored on the centre-plane . The symmetry tells us that if we do the maths of this and try to calculate the lift and drag , that in terms of a vertical force , the force lifting the foil up and the force pushing the foil down are identical , cancelling out and no lift and no drag. Referred to as the DeLambert ? paradox. now put some viscosity into our fluid, a real fluid and look at the trailling edge . The water comes down around the trailling edge and tries to go around the corner and go back to meet the stagnation streamline. If no viscosity then that would be fine. The viscosity tells us we have a different scenario . Viscous fluid does not like going round corners. It tries to run around the bottom of the corner , but it runs out of energy due to the viscosity . So instead it rolls around , and disappears up itself and rolls downstream , the starting? vortex. As soon as we move a foil from static, a starting vortex appears at the trailing edge. That starting vortex disappears downstream. For a good demo of this, when you have abath , put some talcum powder on the water . Get a credit card , carefully place i nthe watr , just 5 or 10 degrees angle of attack and move very slowly. You will see the starting vortex. Same with canoe paddles. Vortices are incredibly powerful , such as tornados. This vortex is very small but very powerful. It acts like a gear wheel. It starts to pull the rest of the fluid , round in the opposite rotation , behind it, circulation. Our starting vortex is going round very quickly , very small diameter , is creating a much bigger circulation of flow around the back of the foil. Again take your credit card and move it thru the water and you carefully lift it out, you will see a little vortex of the starting vortex , going downstream and you'll also see the talcum powder rotating round showing the circulation pattern. A simple experiment you can do at home. Our vortex runs off down stream , the circulation stays that hits the back of the foil and gives it a bit of impetus to change and it pulls the stagnation streamline right back to the ?. When it does that , we've lost the Delamber paradox, lost the symmetry , we're starting to get accelerated flow along the top and higher pressure along the bottom and starting to get the lift force. We can now put a bit of camber or curvature into this foil to control the lift, we can put some thickness in the foil for strenght so it doesn;t snap off. There is a calculation for a flat plate with a small angle of attack , streamlines coloured by velocity . But it gets a bit more complicated. This is a 2D foil with no end to it, infinitely long. With 3D foil we get problems . Look at such a foil from behind and down on top. At the bottom of the foil is high presure, top of the foil is low pressure , the high pressure rolls around the tips of the foil in to the low pressure and rotates dowwn stream as a pair of tip vortices. The plan form of that foil really contols the tip vortices , and they themselves create extra drag, induced drag. When R J Mitchell was designing the Spitfire there was a piece of ironically German theory called the Bettz ? Minimum Energy Hypothesis, that said if you want to minimise tip drag , then you need a lift distributiuon across the foil that is elliptical. So you need a foil with an eliptical shape , hence the Spitfire wing , tryin gto control the tip vortices. A H similar to what we used on the Solent Whisper. If I want to control the tip vortices, control the drag, to go fast and lift the foil and vessel out of the water, I need to look at the plan form. How long the foil is compared to fore/aft dimension. Span and chord , dividing and that is the aspect ratio. A low aspect ratio is short and fat, a high aspect ratio is like a glider wing long and thin. More equations but basically our lift coefficient , measures the lift of a foil depends on the inverse of the inverse of the aspect ratio. The bigger the aspect ratio , the longer and thinner the foil, the more lift you can get. The induced drag coefficient is invesely proportional to the aspect ratio so the bigger the aspect ratio, th esmaller the drag. Al lgood news, if we want lots of lift , not alot of drag a long/thin foil . So a fast jet at one end of the graph and glider at the other end. With Hs there is no single neat mathematical solution. With a short/fat foil , then the ends of the foil don't bend up much , don't deform , no stress within the foil and easy to build . We have low ? of lift , quite a lot of drag and effectively small pressure changes around the foil. But fo r a glider type aspect ratio , then very high tip deflection . If I double the length of the foil , keep the same ;oading , the same shape, the long foil tips will move up and down 16 times more than smaller foil. That creates structural damage. But we also get large pressure changes , that gives us lots of lift. This is where going back to WhiteHawk , get to a certain speed , about 70mph , we hit abrick wall. As we go faster and faster , we start to affect the water around us. A substance having phases, a solid,liquid and a gas phase. For wate r, not in the arctic is liquid. If we play around with the temperature or pressur ewe can convert it to gas. Boling a kettle increases the temp and we get water vapour. If we combine that with pressure then some different effects. Boil a kettle on Everest it will boil at around 70 deg. Hs creating lift as they move along, on the top surface, the pressure drops low enough , that we can turn seawater into wate rvapour. A simple lab experiment of a flask of water with a partial vacuum above it, not dissimilar to Donald Trump. Create a complete vacuum and the water boils at room temp. In slow motion , we can see the inception point is not from heat at the bottom , but nucleating about dust in the fluid body. We effectively build a bubble around our H , if too fast. A water H works far better in water that in a bubble of gas. As we get to the magic 70mph , we start to get cavitation. We can control that to some extent by the shape of the foil. A typical shape for aircraft wing and a typical shape for a H. For the wing , plotting the air pressure on the top of the wing , we'd find the peak of the low pressure , when flying straight and level is close t the nose of the foil . A big peak , then drops off, the pressure recovery, going back to the foil trailing edge. Hs , this one an ekla-H ? ar eparticularly designed so ther eis not the big pressure peak at the front , a nice gentle increase and then amuch flatter line dropping off towards the back. So we have similar areas of lift but the peak pressure is lower, the point where cavitation starts , is much lower. Its referred to in hydrodynamic as a rooftop section. Then we get another problem. Underwater video from our towing tank. A yacht stationary and then accelerating, a keel at an angle designed to create lift a sa partial H, and a certain point it just taps the surface of the water. There is low pressure on the top of our foil , not going fast enough for cavitation , but that low pressure on the foil is attractiv eto the low pressure of the open air above it. The low pressure sucks in air from above , pressure drawdown, ventillation . The carbon fibre strut is bouncing around due to the amount of forces. If our foil is too close to the surface , we get ventillation , we end up in a big bubble and we loose lift. Solent Whisper being tested , you can see a tip vortex appear when a bit too close to the surface, water vapour starting to form , the white line is the water vapour under water. The foil gets too close to the surface , ventillate and the whole foil become covered in a white cloud , loss of lift and a nose-dive. Hobby-horsding along the surface, nose-dive recover , nose-dive ,recover. This is what happened to White Hawk, going so fast cavitation starts, it lifts too close to the surface , looses lift and drops down and with a turbine beehind you while doing 70mph , pretty hairy. So getting H design right to control lif and control cavitsation is really tricky. We need to control the foil. We don't want it too close to the surface , sufficiently underwater so it won't ventillate , so some sort ofcontrol required. Gravity trying to pull our vessel down . In the wate rnormally and not foiling , displacement mode, we have bouyancy force Archimedes. As it accelerates and lifts out of the water our bouyancy force disappears , gravity is still there , a little bouyancy from the foils and w ehave lift. As we go faster and faster , creating more and more lift and the vessel wants to lift out of the water and we'd get to the point of the foils ventilate or cavitate. So for our foils we need lots of foil to lift us and then suppress it so we can just balance with equilibrium of our vertical forces and sail at constant height over the water surface. 2 ways of doing this. 1 is the ladder foil , its what Alexander graham Bell used. Ken Norris described them as Christmas trees under water. At slow speeds and low in the water, all the foils are submerged and creating lift. As you accelerate, the top foils come out of the water and air is 1/1000th the density of water so the lift of the top foil drops by a factor of 1000, ie no lift. So down to 3 foils , then 2 foils and you try and tune the foils to match the weight o fthe vessel. Tricky for Mr Bell as , going along and burning fuel , he was getting lighter, so easier to do with sail as the power. This is the simplest and mos t straightfrward but carrying a lot of dead weight fo rthis and low speed drag. So , for commercial vessels , go for a V form foils. Therre are some additional benefits to this, but mainly as the foil creates lift , more of it comes out of the water and less lift from the parts of the foil left in the watwer . Problem there is oscillation , from ventillation near the surface being drawn down and we need a bigger foil to offset the loss from ventillation. A vicious circle. They work to a certain extent but not hugely efficient. The modern , as used by AC vessels is to use L foils or T foils. On these we can change the angle of attack. The AC yachts will cant the entire foil , forward, level or aft for positive , neutral or negative attack angle, so they can trim for best balance. It is a person doing this, computers are not allowed, a human trimmer has to fly the vesel , playing the angle of attack and get the vessel to run at at a particular height above the water. This is difficult and the early runs required the knowledge and skill of pilots to teach the relevant skill to these human trimmers. For Whisper , a simple mechanical solution , like an aircraft, we build a flap on the trailing edge of our foil . Its difficult to do in terms of structure becuae the flaps ar esmall out of carbon-fibre and the hinges out of kevlar. Behind the foil , called a wand, which has a float on the end and bounces on the surface of the water. We can tune the wand to the foil, so if our boat is too low in the water , the wand is pushed up from the water surface. That works a mechanism thru the board , drops the flap down that gives lift . At the perfect height we make sure our mechanism is such that the flap is level and no aditional lift . If we go too high out of the water , the wand drops down , th eflap ? a tthe back , we dump some lift and the vessel drops back to the original height. A simple mechanical solution but works well. In Whisper we could change the gearing in the system to tune for different ride height ,from 20cm to 47cm above the water. Unfortunately though simple mechanically, it is expenside to manufacture. In terms of materials for building Whisper , the cost is about 20,000 GBP but of that , the one foil is about 5,000 GBP. If you hit the bottom while out sailing then quite an insurance claim . At the tip , the end of the foil is bent down. This is a sharklet? an attempt to try ad control the tip vortices , by changing the lift distribution just a t the very end. Go too thin and it will just break off. One main foil that supports the vessel but if you have only one foil in the middle , you will tip forward or backward so need t support it at more than one point , sovthe rudders have another foil and we can change the angle of attack on those to tune. The design and materials of Hs is such that they must be strong despite a thin foil and not to flex is tricky. A real challenge in designing Hs and getting them to work properly. Thanks for choosing me rather than going to Tim Peake's astronaut talk ,also on this evening, in Winchester Q&A ? ? multiple foils , problem with tuning.? Its difficult to get it to balance up. Requires a certain amount of lift from the front foil , certain amount from the back foil and need to balance the two. The control we used was like a motorbike, a twist grip for the rudder and change the rear foil and angle of attack to balance up. The fastest that boat got to was over 30 knots. With the tendency towards climate change, there is big urge to reduce the power consumed by large ships, is there a large ship application for Hs? This is another area where Hs have an upper limit. an upper limit of about 600 tons. As you scale your vessel up , the weight of the vessel goes up with your scale cubed. Double your weigth and 2x2x2 . The lift generated from the Hs as you scale them up , scales by the surface area, so squaring. So scale up and not enough lift is possible. The power for a motorised H is quite large and in terms of passenger carrying capability , dependent on the deck space , you can get far more seats on a wide catamaran than a relatively narrow H vessel. The efficency commercial driver for passenger transit is to go for catamaran rather than H. For smaller vessels, use of Hs to reduce power, in controlling th e flow around the vessel . For small commercial vessels, we still need to get thedrag down more, then that would be possible. Last week was the announcement of the world's first diesel-electric hybris pilot vessel , the next developement to that will include Hs for efficiency purposes. If and when you hit something , firstly do they have shear-pins and secondly I went to IoW yesterday on a Red Jet. It was spring tides and low tide. I'm aware that spring tides lifts all sorts of nasty stuff that otherwise sits beached on the land. I have seen a big bit of ex-quayside baulk of timber weighted down by large ironwork so neutrally boyant and only just piercing the surface. Yesterday the vessel turned at Town Quay and started to pick up speed and there was a great clunk , you could feel through the hull and seat. He slowed down to a full stop and he did not go backwards and nothing came over the public address. I was trying to imagine what was going on. Perhaps he hit something on the bottom , as low tide, would he have had underwater cameras to see if he'd snagged a chain or a something and could see if it dropped off if he reversed? Undoubtedly what happened was something got sucked into the water intake , the depth there at low tide is 12m so plenty of water under them. The prime candidate would be a plastic bag , sucked into the intake, that would shake the vessel . This would have been cavitation , changing the flow into the water-jet unit , causing the impeller to cavitate , which is very violent , and the whole vessel shakes. Cavitate for too long and its perfectly possible to eat holes in the blades of the impellor. A fairly common event, due to the huge amount of debris in the water , natural and otherwise. Neutrally bouyant debris , typically carrier bags are the prime candidate. The shear-pin business, designed in for worst case ? You would design a fail-safe scenario . For racing vessels and high speed sailing vessels , you can make the risk as low as reasonably practical but can't negate the risk. The fisrst Whisper prototype , was sold to people who accidently hit Sweden with it. That removed the foils and did a fair amount of damage . You need it to fail at a certain point, but not rip the hull to bits as well. Rip off the foil and that disappear cleanly away rather than risk hull integrity. Red Funnel Shearwater Hs when they wer running pure Hs did loose a front foil once , the hull nose-dived and came up again . Scared everyone but no one injured. Rather than the catamarans which had foils to help the drive control , Red Funnel about 20 years ago had full Hs that would lift the vessel completely out of the water. They were built in Italy, still actually operating in Ireland. Similar to hitting debris, once you are up on the foils and moving quickly , if there is a lot of other traffic around you , navigation becomes difficult. The current red-jets if they want to stop quickly , they can just drop the buckets at the back of the water jets and it will settle fairly level , fairly quickly in a few boat lengths. With full Hs you have more distance to carry and in crowded waters that is risky. I was thinking there may be some sort of gyroscope action and that a H craft could not turn on a sixpense.? It depends how much you want to scare the passengers , a relatively good turning circle but it will bank very steeply. That asymmetric system for the 2021 series. I would have thought the forces on a simple blade keel were bad enough , but an off-centre H arrangement , looks like pretty horrendous forces involved? The whole thing just does not look right . For that assymetric structure I can't imagine what the internal bracing must be like? Its probaly milled titanium with a carbon skin around for the hull. They will be interesting , there is a move afoot I believe, that says lets work together on some of these really complicated components and then we'll see who is the fastest when it comes to driving them. Have you pics of those Americas Cup 21 series sailing? No generic name for them , not assymetric foil or anything other than AC 21. Some next generation H sailing boats. They look terrific fun but I'd not go anwhere near them personally. Flat out in the Southern Ocean they'd be doing 30 knots. Is there a sweet spot for the depth below the surface for avoidance of bumping or whatever? Debris is at all heights in the water column , but if your H is too deep under water , there is a lot of supporting strut to hold it , additional wetted surface area and extrra drag. If too close then ventillate or cavitate and so extra drag. So a lot of time spent trying to find the sweet-spot , 1m under water, 2m under water . All quite difficult to test at model scales, it can become an expensive process. For Whisper it was cheaper to build the full-scale boat and suck it and see. There are no servo-systems built into that control system? The loads going thru the foil are so great , to create an electo-mechanical system to try and move the H up and down is probably something possible in theory only. The weight of the kit would probably negate any benefit. W96

Tuesday 21 August 2018 Prof Mark Cragg, Soton Uni - Antibody immunotherapy: overcoming cancer by engaging the immune system Antibody immunotherapy (AB I) and how we use it for anticancer treatments. We're based at the SGH, just moved to the new site of cancer I. Some general introduction to ABs, monoclonal (MC) ABs which is what we use in the clinic, ABs that are now treating patients successfully, fovusing on 1 AB I've spent 20years working on Rituxamab (R) and how it works. A paradigm on how lots of different types of ABs work. The target of that AB is a molecule called C20, discussing other C20 MC ABs and some of the other ABs now being used in the clinic. An AB is a Y shaped molecule , it is dimeric 2 identical domains to the sides with a line of symmetry. The bits , the variable domains , the bits that do binding. ABs are essentially recognotion molecules, the bit at the bottom is the Fc domain which does the interaction with the I system. A ctrystal structure of what an AB looks like in 3D at the atomic level. Then ribbon colouring to show where different parts of that AB are. The FAB domains are identical on eithe rside, the Fc domain at the bottom . The bits inj the middle are sugrs, carbohydrate part of that molecule that helps keep this in the right orientation and structure. The important parts of the molecule , as d=far as AB function is to do with recognition. The loops ar ehypervariable loops and they are different between different ABs. One area is particularly hypervariable , each having a unique sequence particularly in that one region . Within your body , the diversity of ABs is enormous. So w ecan recogniose billions of different types of molecules , because the sequences in thwese regions are different. When I say they combine to specific targets, they try to recognise specific things. Its all part of what the IS does, differentiate between self and non -self. We are trying to recognise the difference between cancerous cells an d normal cells. ABs have the problem that many molecules llook similar or are quite different and we need to be able to distinguish between them. ABs will bind with one very specific molecule , and ignore all other molecules. This is important when distinguishing between self and non-self, pathogens ,bacteria,viruses all those , compared to normal human body cells. One of the primary things ABs are involved in is fighting infection. Al lthe time lots of circulating ABs in your blood. They are recognising those different molecules, particularly molecules on viruses and bacteria. The way they are generated in the body -we have 2 phases. A primary response , when first exposed t ta pathogen , we generate ABs. It sees the pathogen snd removes it from the body. The beauty of the IS is that it has the capacity of memory. If you encounter the same pathogen agsain, you are immunised, having had memory of encountering thst same pathogen . when encountered the second time you get a much bigger response. And a much more rapid response. The magnitude of response the second time is 100 times bigger. So we can fight off infection. Instead of feeling ill before the system gets going. This way the repsonse gets going before we can feel ill. Wha tpeople have been trying to do for the last 100 years is to understand their utility possibility for treating different types of diseases. Particularly for anti-C treatments. Paul Erlick had the idea of magic bullets , postulating that ABs existed before anyone had any physical evidence for that. Way before we had structures , before we could clone things or any of the moder=n biochemical tricks we have these days. He postulated the body could recognise things . Then nothing for 60 years. Millstein and Khola in the 1970s found a way for ABs to be generated in the lab. They demonstrated ABs and could isolste them and grow them in the lab. In the lab they made MC Abs. The different ABs are recognising different parts of a virus, hundreds of things on the cell surface differnt from humans , generate aBs to each of those different biits . We can generate different ABs to diferent parts of a specific molecule . So lots of ABs involved , of different specificity, a polyclonal response. Lots of different ABs mounting against one particular pathogen. Khola and Millstein generated MC ABs by taking a single immune cell, a B cell or a plasma cell, a normal cell for making ABs and they physically fused it with a chemical PEG so 2 cells fusing and the cell they fused it to was an immortal cell , a myoloma cell. A cell capable of producing lot of protein. So a single B cell which can only make a single specificity of AB with something that was immortal and would contine to produce that particular AB. They won the Nobel Prize for this. 30 years ago, now we use them for a lot of detection kits, pregnancy detecting stem cells, cancer cells in the blood , and for diseases the early detection of cardio-vascular disease, deep-vein thrombosis. This is the specificity of ABs , of great use for detecting, binding to something uniquely. A massive repertoire of their bility to recognise something. But these days we are starting to use them to treat diseases. To treat neurological disorders, auto-immune diseases , allergies and treating C. We are trying to recognise something different about a C cell. So an aberrant protein , something expressed differently on a tumour cell , not expressed on the normal cell. Then get an AB to recognise it and then in some way interct with the IS to destroy it. So why do we need new therapies, whats wrong with things like chemotherapy. A plot representing evolution of chemotherapy over a few decades, for treating lymphoma, B-cell cancers, blood cell cancers. Each line is a ore intense/more agressive chemotherpy , so capacity to kill cells with increasing intensity . But this survival curve shows it makes no difference, chemo can only take you so far. For the patients surviving out to 5 years , chemo has done a good job , but all the others have not survived. Getting more intense chemo will not work. So the use of MC ABs to use the IS to fight cancer or disease. So the AB using the variable domains will find something specific on a tumour cell, and engage the IS. The IS has multiple ways it can delete a cell thats been tagged by an AB. A protein component in the blood C1q , a member of the complement system , of a protlytic cascade and can also interact with receptors on immune cells. The reptors that find that in the Fc are called Fc receptors. Fc means it was fragment crystaliseable , one of the first parts they could crystalise and so getting the atomic structure , very early on. It was particularly straightforward to do that. So we'll bind an AB to a C cell and get the IS to delete it. Since 1997 this route has worked , for effective therapies. A curve since the first years of getting ABs thru into the clinic, approved therapies. So in 1997 there was 6 . The original ABs were mouse ABs , mous eB cells , the mice had been immunised with a human protein , the mice made an AB to that human protein, then the cells were immortalised to make the MC AB. The first ones to go into humans were also mouse ABs. Putting a mouse AB in a human will probably generate an immune response and get rid of the AB. This happened , so subsequent generations of ABs became firstly chimeric the Fc part of the AB that was mouse was then changed by genetic engineering to become human. So much less of a problem as less of the AB was derrived from mouse. More recently as we've got more sophisticated with microbiology tech, we've either humanised or generated fully human ABs. Humanised is where we took the mouse sequence , and look at the human sequence noting which bits ar edifferent between mouse and human and convert them with molecular biology. For human we generate them originally form human B cells using cloning techniques or we do a phase display library , where we take all the possible B regions and do some selection in-vitro , not in an organism. The original ABs were generated by immunisation via mice , now we can take human B cells , isolate all the different AB molecules and then a panning technology to identify things that bind to the things we are interseted in. So fully human ABs. Since 1997 essentially an exponential increase in the amount of aBs that gain approval. I looked at the table yesterday and we are at 70 or 80 ABs approved. Plus 100s in phase 1 trials , on the route to come through, phase 2 and phase 3 . This will continuie for at least the next decade, with all the ones just starting thru at the moment. Canonical means just normal ABs in terms of their structure and function, just the same as the wild type ABs , normal ABs . Non-canonical where we're a bit cleverer and identified a particuar function of an AB is either useful or not useful and then augmented or removed it. C1q is one way the ABs can target a cell, the C1q binds , then a cascade that enables various things that happen with a complement cascade. One is we get immune activations , we get release of anaphalatoxins where you get redness and swelling inflammation. C3a, 4a/5a they bring in the immune cells to the point where these things are released. You can get coating of part of this cascade C3b which targets the cells where this activity is stimulated. This gets coated on the cell surface and in there ar evarious cells that have receptor components C3b which again allows a recognition and destruction of a target cell. Then a membrane attack complex , a multi-protein complex forming which physically punches holes in a plasma membrane of a target cell. The Complement Cascade A second thing we can take advantage of , all these receptors especially when talking of targetting C cells, are there for a reason. There not there so we can conveniently tag them with ABs , they are doingg something generally. So if a tumour cell has upregulated a protein , its probably there for a reason. THat means when we then bind it with ann AB , you potentially perturb the signalling that comes from that particula molcule. Then lastly the ineraction between the Fc and the Fc receptors on various immune cells and particularly importantly are cell types such as macrophages and natural killer cells. Anyone studying biochemistry has to learn about complement cascades, 20 protein complexes with lots of things leading to lots of other things. It starts with the C1q protein , that does the recognition , it recognizes when Fc parts of the Abs are close together, so you need a certain orientation of these Fcs to C1q , to bind. That starts the cascade, conformational change happens when they interact and they start the protolytic cascade of cleaving , C4, C2 comes in and cleaves to form a C3convertase, essentially a whole process of proylytic cleavage , releasing the next fragment that goes on to start the next cascade. It ends up with the MAC which has polymeric amounts of the last component called C9 , one molecule of C8 , C5b the coating on the cell surface. Its essentially punching holes in the plasma membrane, which then allows those cells to be destroyed. In terms of signalling , ABs can do various things , they can physically transmit a signal thru the receptor that causes growth inhibition or death of that cell. It seems counter-intuitive as to what a tumour cell would want to do, by upregulating on its cell surface, but unless there is any selective pressure, for that receptor to be detrimental , then why would it down regulate it. If it just happens to be a particular cell that evolved and has a particular receptor , which can target for destruction , we can take advantage of that with our AB. Thts certainly the case with anti-ideotype AB. Also ABs can block a positive signal coming from a receptor cell surface. If a tumour has upregulated a protein , to help it grow/proliferate/survive , then using an AB , we can block that signal. Either blocks the receptor interacting with other receptors on the tumour cell surface or it can block interaction between say a growth factor and a growth factor receptor. This is what happens wiht hte drug Herceptin , which is an aB that binds to a receptor called Her2nu, which is over-expressed on a proportion of breast-C patients. One of the successful treatments for secondary breast-C after initial treatment. ABs can also block host / tumour-cell interactions, a particular thing of interest when we consider mestastasis. When a C metastasies to a different site , it then has to generate its own vasculature. It has to get blood vessels, get nutrients into it and it upregulates the protein VegF and we can then generate ABs that block VegF , so we can stop that process, or happening less efficiently. This is hte action of the drug Avastin . These are AB drugs , that you may not have known. THe bit I'm interested in , fo rthe last 10 years. Fc receptors tht engage cells of the IS not just the cascade complement. An interesting but complicated family of receptors , parallel systems activating in mouse and in humans. Humans have to be more complicated than mice , but the principle is straightforward. We have Fc receptors that are either activating or inhibitory. Activating ones stimulate cells of the IS and inhibitory ones inhibit cells in the IS. They do that with different signalling molecules on the inside of the cells. The only real difference between the mous eand the human system is tha t we have more members in the human family . This happened during evolution , duplication of the whole genome locus and we got twice as many. They are highly conserved when you look at their sequence and structures. For understanding how these work, I'll go thru some gene-KO studies we've done in mice. One is the gamma-chain Knock Out. The gamma chain is associated with all the mouse activatory receptors, meaning that if we have a gamma-chainKO, none of these receptors are expressed or signalled. We can they say , are these gamma-chain receptors important for the function that we want to study. We still have the inhibitory receptor left , because that doesn't need the gamma-chain for signalling or expression. 11/0/20 22/62/41

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