Seriously Small Structures

Scientists monitoring pigs in Hong Kong have spotted human H1N1 swine flu rearranging its genes.

Writing in Science this week, Hong Kong University researcher Dhanasekaran Vijaykrishna and his colleagues describe how, by monitoring samples from pigs sent for slaughter, in January 2010 they picked up a new strain of swine flu with unknown pandemic potential.  Owing to the perceived threat that pigs pose by acting as molecular mixing vessels permitting swine, bird and human flu strains to swap genetic material, the team have been monitoring the Hong Kong abbatoir for over ten years.

Between January 2009 and February 2010 they picked up 32 cases of flu amongst pigs, including classical swine flu strains and (since October 2009) cases of the H1N1 swine flu that caused the human pandemic.

But the virus detected in January was different. It contained the core molecular workings of a circulating strain of swine flu but also had acquired the haemagglutinin (H) surface coat of the human H1N1 pandemic strain.  This shows that the human pandemic strain, when it enters pigs, can clearly "reassort" with other pig flu viruses, potentially generating novel pandemic strains that might have enhanced virulence amongst humans.

Tests carried out by the researchers showed that the new strain could transmit readily between the pigs, indicating that it was fully infectious, although it tended to produce a mild illness.

Nevertheless, this observation should serve as a warning, say the researchers, that more widespread surveillance of pigs is crucial in order to help us to predict and mitigate potential future threats to public health.

Scientists have found a way to use gene therapy to combat HIV infection.

Although drug therapy has revolutionised the treatment of HIV, it is not curative and inevitably patients still eventually succumb to drug-resistant forms of the virus, treatment-related side effects or cancers such as lymphomas, which occur much more commonly amongst HIV-infected individuals.  Part of the reason why HIV is so hard to treat is that the virus lurks inside the human genome, inserting covert copies of its genetic material into the host DNA where it sits out of reach of the effects of drugs or the immune system.

Consequently, in recent years, scientists have been attempting to develop "genetic medicines" that can target this hidden form of the virus.  Previous attempts to carry out "gene therapies" in humans, for a range of different diseases, have produced mixed results and are often hard to justify on ethical grounds.

But now a team based in California have provided encouraging evidence that such a strategy might work.  Writing in the journal Science Translation Medicine, City of Hope scientist David DiGiusto and his colleagues explain how they have safely and stably genetically modified the immune cells of seven HIV patients to make them resistant to HIV.

The team first collected non-HIV infected blood stem cells from the patients, who were undergoing treatment for lymphoma, a blood cell cancer that occurs more than 100 times more commonly in patients with HIV.  Working in the culture dish, the researchers then used a disabled virus to add to the cells several genes that interfere with the growth of HIV.

The cells were then maintained in culture for a further period of time to check that they were safe before they were reinfused back into the patients where they took up residence in the bone marrow and began to produce new blood cells.

Checks on the patients' blood confirmed the presence of cells carrying the anti-HIV genes two years later, when the study ended.  This shows that techniques like this can be used safely to protect immune cells from HIV infection.

Next, a much larger study, in which higher counts of modified cells are administered, will be needed to determine whether this technique can aid the elimination of HIV from the body.

Chris - Also in the news this week, a new type of material, one that gets thicker rather than thinner when you stretch it, this is called an 'auxetic' material is being developed by EPSRC fund of researchers and they're trying to provide better protection from the effects of bomb explosions.  Jane Reck spoke to the inventors who are based at Exeter University.

Jane -   In this research laboratory, cutting-edge science and technology is getting a helping hand from an old fashion machine, a traditional craft loom.  But instead of weaving cotton for clothing, it's making a completely new type of fabric.  It's a material that will give much better protection from the effects of bomb explosions and severe weather events such as typhoons and hurricanes.  The project uses auxetic materials and is led by Professor Ken Evans at the University of Exeter.

Ken -   An auxetic material is unusual in that it's a material which when you pull it, does something that you would not normally expect.  If you imagine pulling a rubber band, two things obviously happen when you pull it.  It gets longer and at the same time it gets thinner, and this is a very easy thing to see with a piece of rubber, but that's the fact with the case of any material.  If you could pull a piece of steel, you would find it was getting thinner as it was getting longer.  Well auxetic materials do exactly the opposite.  When you pull them they get longer but at the same time they get fatter.  This particular project is about blast mitigation.  It's about using auxetic materials to make a textile which we can then produce a curtain material from which will act to mitigate blasts in an explosion situation.  And auxetic materials we believe have particular characteristics that will mean that they absorb energy much more effectively than the current conventional materials.

Jane -   The hands on work of identifying which materials need to be used, the manufacturing and testing of the yarns, and analysing the results of those tests is carried out by Dr. Mike Sloan.

Mike -   The really useful thing about this research is that we're taking conventional fibres.  So these are fibrous materials you can buy off the shelf, so you're talking about stretchy materials, elastomeric materials like polyurethane and then you're combining it with a higher performance fibre like Dyneema, people probably have heard of that.  Also, ultra high stiffness carbon fibres and it's the method in which we combine and it gives you auxetic effects.  So it's conventional materials in a helical arrangement that gives the auxetic effect and there's a number of parameters we can change.  We're looking at the stiffness ratio between the two fibres and also the angle at which the second fibre is wrapped around the middle fibre.  We designed and built a purposely designed spinner here at Exeter and we can load our core fibre onto a single-spool feed spool that's taken up at the end on a take-up spool. And we just program in the relative speeds of the actual spools and that will manufacture a yarn - very accurately controlling what we called the 'wrap angle' so how tightly the wrap fibres wrapped around the core fibre.  Then that yarn will then go back to the mechanical testing machine and I'll add on some extra hardware that we've got and will characterise its mechanical performance, but also shape change, how auxetic is it. 

When it gets this much longer, how much wider does it get?  Then those most promising yarns will go forward onto our loom.  The loom that we actually use is designed and sold as a craft loom.  There's nothing special that we've done to the bit of equipment.  There's no modifications that we've made.  The only thing we do is these are auxetic yarns to make an auxetic textile, and by using a computer controlled software on the loom, we can actually change the weave pattern as well so we can go from a straightforward, what we call a 'checkerboard weave' right up to complicated twill weaves.  It's at another parameter that we can change using the loom as well.

Jane -   A crucial part of the design process involves the computer modelling work carried out by Julian Wright, a research fellow at the university.

Julian -   If we want to make enough yarn to make a curtain-sized piece of fabric for example, that will be several hours' worth of time.  So that's a very expensive mistake if we don't get the yarn right at the design stage.  That's a key facet of the computer modelling, is to be able get the yarn right without actually having to spend hours making it and then seeing it if it was right.  We want to know it's going to be right when we've made it.  The computer modelling at this stage is concentrated on the yarns.  So we're not yet modelling the textiles and we're certainly not yet modelling the explosions.  We're specifically interested in how will the yarn behave when we stretch it, how fat do we need to make it, how stiff do we need to make one or more of the components, what angle do we have to wrap the helical component at, how far can we pull it.  One of the major parts of the modelling activity at the moment is to be able to predict the behaviour of the yarn from a knowledge of the two components.  We know what polyurethane's like.  We know what polyamide is like for example.  What we would like to know is if we wrap those two together, how will they behave?  The major achievement so far of the research certainly in the context of computer model is that we now have very detailed knowledge.  We understand very well how to design a helical auxetic yarn.

Jane -   The tests that the team have used to put the material through its places show that the shockwave from a bomb blast travels more than 1500 miles per hour.  Ken and Mike explain what the tests have shown.

Ken -   The very first thing you see is the light that comes from the blast, and then a pressure wave arrives from the explosion, and that moves the curtain inwards as you might expect it to do.  And then following on from that, you then get destructive damage.  So if you have a glass window, the glass shatters and breaks.  Now what happens is the curtain is moved by the pressure wave first and because our fabric is auxetic, it opens out in a particular way. The curtain at that stage is not damaged by the blast at all.  So the glass fragments then arrive after the pressure wave and are essentially captured by the curtain.  And at this point, the curtain starts returning to its original shape.  It stops ballooning out.  It moves back in the other direction.  And in fact, what we see is the glass fragments collected and essentially thrown back, almost like a trampoline effect, back out of the room.  So you can see the energy absorbing mechanisms taking place while this process is going on, and what's been particularly useful is to be able to do the test with very high speed cameras to see exactly what the mechanisms are, so we can understand how the total process works.

Mike -   Not only have we watched the blasts under high speed video.  We got pressure sensors before and after the curtains and the two things that are really interesting are the peak pressures that we measure, but also the time duration, and when you take the area around of that curve, you get what we call the 'impulse' and that's really the energy that's experienced as a function of the blast.  And our preliminary data are showing that curtains give a 25% reduction in that impulse.  So the 25% reduction of the energy that somebody the other side of the window would experience, so it's looking really promising, and you know, we can only go forwards from here.

Jane -   Ken hopes it won't be too long before we see the fabric in general use.

Ken -   I would say that within 5 years, you could see commercial fabric on the market, providing they meet the promise that we believe they're going to do.

Chris -   That was Ken Evans, Mike Sloan, and Julian Wright from the University of Exeter and they were talking to the EPSRC's Jane Reck.

&nb

Chris - Now we all know what happens to water when it freezes.  It becomes ice, but it does some weird stuff as well because the ice is less dense than the water and it floats, and there are still lots of unknowns about how this sort of transition from water to ice actually happens, especially on the nano scale.  So understanding this could help with a wide range of different industry applications, as well as our predictions of what will happen with climate change.  So this week, Meera Senthilingam went along to the London Centre for Nanotechnology to meet Angelos Michaelides to find out how his team are looking at how water turns into ice.

Angelos -   There's really many, many interesting things about water.  It's an everyday substance - we're made of water.  It's all around us.  Our Earth is covered in water, but we still don't understand many of the properties of water at the molecular scale, and one of the processes we're trying to understand is just how water freezes; how individual water molecules come together to form little ice particles.

Meera -   Well why does ice form in the first place?  So why does water become ice?

Angelos -   When we're below zero degrees, ice is simply more stable than water.  Most of the times when water freezes, it happens at the surface of some impurity particle, and so, it's the actual presence of these little impurity particles, maybe minerals or clays or dust particles that actually allow you to nucleate ice.  The water will stick to the little particles, form a little ice particle, so this is a nucleation process, and then once you have a small ice particle, just like in crystal growth, it's very easy for more water molecules to stick to the little crystal and to grow, and to expand.  So we really want to know how exactly, looking really at the level of individual molecules how this ice forms.

Meera -   More specifically, you look at this formation of ice on particular materials or solids such as metals rather than just how ice forms in the first place.

Angelos -   Yes, so water really is one of the most incredible substances that we have.  It occurs in our environment in all three phases, solid, liquid, and gas, and in the solid phase, there are 15 different phases of ice alone.  And so, you can imagine when you introduce some other material like a surface, then you get all of this beautiful array of complex and interesting behaviour.

Meera -   How do you set about looking at this?

Angelos -   One of the techniques that has really transformed our understanding of water at interfaces at the nanoscale, is the scanning tunnelling microscope, and this is an incredible technique that allows you to see individual molecules and atoms at surfaces.  And then we will take this experimental insight that comes, and we will try and build models to really understand at the molecular scale how these structures form, what structures form, and why.

Meera -   And so, what have you manage to find out so far then?

Angelos -   Well one recent example that was interesting because it went sort of against common belief was where we were looking at water on a copper surface, and we noticed that water forms chains.  And when we did our models to understand what is the structure of these chains, we noticed that the water is actually forming pentagonal arrangements.  So it's actually forming chains built out of water pentagons.  This is interesting because we know from daily life that snowflakes come as hexagons and have this hexagonal motif, and out of all of the 15 different ice phases, none of them are actually built out of pentagons.  If we go to another surface for example, if we go to a palladium surface, we don't form pentagons, but we don't form traditional ice-like structures either.  We form something that looks like really beautiful rosettes, and a lacy structure.

Meera -   So that's really quite fascinating that it just varies so much on different solids or different metals in this case.  Now you've also been looking at the formation of ice on clay particles which is important for understanding our atmosphere.

Angelos -   Yes, so when we're starting the formation of clouds, this typically starts off with a super cooled water droplet.  So a small micron-sized water droplet that is already below zero degrees, but it won't freeze at super cooled.  This freezing process is helped by a foreign substance which in the atmosphere, quite often is a clay particle.  Little nano-size clay particles typically float about in the atmosphere.  They get there from dust storms in desserts.  So we're interested in understanding these clay particles and how they make the rain, and make the snow because without these agents that would nucleate the ice, it simply wouldn't rain.  Outside the tropics, we require ice nucleation to have rain.

Meera -   I mean, it's clearly interesting to understand this simply to know why it does rain as you've just mentioned, but what are the applications of potentially of knowing this about the formation of ice on so many levels or on so many materials?

Angelos -   In the atmosphere, we want to know how and why ice forms if we want to understand issues like global warming to understand the impact of ice and clouds, and water in the environment, and how it impacts upon - say for example, the temperature of the globe.  Aside from this sort of environmental interest, there's all sorts of technologies who are interested in ice nucleation. 

One example would be the airline industry.  Their planes, as they're flying through these super cooled water droplets at minus 30 degrees, it's incredibly useful that ice doesn't form on the wings, on the fuel lines, all over the planes.  Like that plane for example that crash landed a couple of years ago at Heathrow.  It did so because ice formed on one of the fuel lines which cut off one of the engines.  So there's an industry who are very worried about ice nucleation.  Ice cream manufactures are also interested in this.  Ice cream doesn't taste very good if it's covered in little icy particles.  And going back to the atmospheric connection, it's incredibly important for these people who want to control rainfall, who want to so-called 'seed clouds' to make it rain.  They're interested in knowing what is an efficient material at making ice so as to make rain, and one of the most widely used materials is silver iodide because it has a structure which resembles very closely the structure of ice.

Meera -   So that's quite a wide range of applications.  So, what's the next step in this research then, in order to help this wide array of industries?

Angelos -   At the moment, we can identify what structures form and we can understand why, but we're not at the stage that we can predict.  So we would ideally like to be able to predict and to say, "Okay, you give me a material and I'll tell you in advance how it will behave", to try and identify the basic principles and the basic trends that control ice nucleation at interfaces.

Chris -   Who would've thought the most common molecule on the earth within - well, a few words of magnitude, could be so complicated.  That was Angelos Michaelides.  He's from London Centre for Nanotechnology which is a collaborative institute between UCL, University College London and Imperial College London.  He was talking to Meera Senthilingam.

Sarah: -  Now, lithium ion batteries are an essential part of most of our everyday lives.  They're in our mobile phones, our iPods, and our laptops, and they can be used for hybrid or electric cars, and for storage of electricity from renewables like wind turbines.  For each different job, you're looking at different properties whether it's fast-charging time, efficiency, safety, or cost.  At the moment, there's a trade-off between these properties, but nanotechnology could offer a solution.  Professor Clare Grey from the University of Cambridge is looking at how...

Clare: -   A battery comprises three main components.  You have an anode and a cathode, otherwise known as a positive or a negative electrode, and they're separated by an electrolyte which in most lithium ion batteries is an organic solvent with a lithium salt that allows the lithium to shuttle backwards and forwards.  Now if I want to charge a battery very quickly, that means I have to get the lithium and the electrons in and out of my particles in the electrodes, and so your commercial standard battery material in the cathode is lithium cobalt oxide, and that's a material that's many microns in size.  And so, when I charge the battery, I've got to pull the lithium out of this micron-size material and that takes a long time.  And that's why it takes you a long time to charge your battery for your cell phone or your laptop.  But if I could make the particles smaller, then I would be able to do this much more quickly and get a much higher rate material.

Sarah: -   Nano structures would seem to be the ideal candidates of this task as their small size and large surface area would allow for quicker reactions, leading to quicker charging times.  But it's not all plain sailing.

Clare: -   There are some very good things about nano, but there are also some disadvantages, and one of the major disadvantages is the surface areas.  And so, if you have high surface area, you have a higher potential for side reactions with the electrolyte, and most nano materials and battery materials are not actually stable in the organic electrolyte you use in your batteries.  Now what happens is, as you're cycling material, they form a passivating layer, a coating of inorganics and organics on the surfaces of the materials that protect the material from further attack by the electrolyte.  But now if you imagine it's nano-size, you have a massive surface area.  And so, that whole decomposition to form this passivating layer eats up lithium, and you have a finite amount of lithium in your cell.  So the more you eat up, the less you have to use in your battery application.  Another disadvantage with nano particles, because you can have so many side reactions, is if you have too many side reactions, the system can heat up. 

Once the system starts heating up, many meta-stable materials can release oxygen.  It's the oxygen that then reacts with the organic electrolyte and at high temperatures, that electrolyte can catch fire, and it's that electrolyte burning that you see in many photos on the web of batteries exploding.  And so, if you examine the pros and cons of nano, it's clear that nano materials and nano structured materials allow you to get your lithium and electrons in very rapidly, and so, that's going to be a massive advantage when you want high rate systems.  But it's going to be a disadvantage if you're looking at safety.  I think there are some solutions that will allow us to use nano structures, but it's a very, very important design criteria that we need to build safety into our design.

Sarah: -   And Professor Grey's work is helping to examine exactly what those solutions to the problems with the use of nano structures in batteries might be.

Clare: -   We're very interested in working out the fundamentals by which battery materials function.  So how do the lithiums come in and out of the materials. We do that because if we understand how they function, we can use that to design better materials, and we can also use that to understand why sometimes they don't work.  So what we've done recently that we are very excited by is we've developed a setup, whereby, we can make little batteries that are about the same size as hearing aid batteries. And we connect them up to a potentiostat and that potentiostat is just like a battery charger you might have at home, except it's a little bit smaller, and a bit more accurate.  And then we make use of the fact that lithium has nuclear spin that you can see in an NMR spectrometer.  So that allows us to see where the lithiums are going as we charge the batteries. 

The exciting thing for us is that we can see functioning in real time, all the different components, and we can work out what each component is doing and how each component is influenced by things like charging fast.  So when you're wanting to charge your battery for transportation applications, or if you're using a hybrid electric vehicle and you put your foot on the brake, that requires an extremely rapid charge, and that puts tremendous demands on your batteries, and that often in itself encourages the formation of side products that then may have negative consequences on how the battery then functions, and the bottom line is we can see this in real time, and we can try and device strategies to prevent that happening.  So we're looking at function and structure, and then trying to use that to then design newer systems or improve systems that both last longer, and more safe.

Sarah: -   And if you've ever seen a battery self-ignite, I'm sure you'll agree that safety is paramount.  That was Clare Grey from the Department of Chemistry at Cambridge University.

We put this question to Professor Stephen Bennington from the Rutherford Appleton Laboratory...

Stephen - Well it's like digital technology, so it's using electrons. But instead of just having on and off as your two states, you can use the spin of the electron so that spin can be up/down, and so you have much more information in there. But instead of using silicon, you can't just use silicon for these kinds of things. You've got to use much more complicated magnetic materials and you've got to make them nano scale. You know, silicon at the moment is at 45 nanometre, so you've got to make these complex materials also nano scale. We do a lot of work on this at the Neutron Source which is very good at looking magnetic materials.

We posed this question to Professor Stephen Bennington from ISIS at the Rutherford Appleton Laboratory...

Stephen: - Well I know there's water up there. NASA scientists have discovered this recently, but there's no hydrogen as far as we know. I've not seen any reports of it. Hydrogen will only stick on surfaces either below 20 Kelvin or in very thin layers up to perhaps about 50 Kelvin, and most of the moons are higher temperatures than that. There might be little dark areas whether it's cold in there, but on the whole, no. Chris: - But the fact they found water out there with the mission to slam the probe into the south pole of the moon, means that we can just get the hydrogen we need by extracting the water and electrolysing it presumably. Stephen: - Absolutely, yes. Chris: - So it shouldn't be a problem.

Chris - The answer is, yes, they do. The gene which enables us to see red light, in other words, encodes the red detecting pigment in the retina is carried on the X-chromosome, and because women have two X-chromosomes that they inherit from their parents - one from the mother and one from the father, they therefore have two genes in their body that are capable of detecting red.

But during development, one of the X-chromosomes is randomly inactivated. This is called 'X-chromosome inactivation' because you don't want two copies of the chromosome active because you only need one because men only have one copy. But that process of inactivation is random in the tissues which means that some cells will be using one X-chromosome whilst other cells could be using the other X-chromosome, and therefore, if you extend that to the retina, there'll be some cells in the retina that are seeing red, using the gene on one X-chromosome, and some cells seeing red using the gene on the other X-chromosome.

And this means theoretically, there could be different genes running in different bits of the retina, and therefore, the perception of red could be slightly different in different positions on the retina in women. But because men have only one X-chromosome because our genotype is XY, we therefore don't inactivate an X-chromosome, and therefore use the same gene throughout the retina, and that's why you also find men who can be colour blind because they can inherit a red receptor that doesn't work. Whilst women, because they have two X-chromosomes, even if one of them has a defective copy, the other one is almost certainly still going to work and therefore, in general, you don't find women who have colour blindness. So the answer is yes.