Features

The hawk moth's wings are a blur of mottled grey motion as it hovers tethered to a steel rod in large white plastic orb. Outside the orb in the darkened room where I stand, a projector casts moving patterns of dimmed light onto the sphere's surface, illuminating the moth's field of vision with oscillating stripes.

Tonya Muller, a DPhil student in Oxford University's Department of Zoology, sits at the computer controlling the experiment. At regular intervals, she directs the computer to alter the direction, amplitude and frequency of the light stripes.

These changing light patterns create altered visual environments for the moth inside, which aim to simulate real-world visual disruptions the moth might experience when exposed to wind gusts. As the patterns change, the moth makes rapid adjustments to its flight behaviour to maintain constant stability.

Though imperceptible to the human eye, the moth's responses to the visual stimuli are detected by a force sensor attached to the end of the steel rod and relayed to Tonya's computer. These recordings are helping Tonya to understand the moth's remarkable visual-motor system, and identify the mechanisms of visual feedback in insect flight control.

'Understanding vision-based flight control in insects has far reaching uses in the fields of sensor development, signal processing, and robotics,' says Tonya, whose background is in mechanical engineering. Vision is important for information gathering in insects and up to 50% of an insect's brain can be composed of visual neurons. In fact, despite their small brain size, insects can solve extremely sophisticated orientation problems both rapidly and reliably. Yet their eyes are far less sophisticated than our own.

'Insects receive visual information through a relatively noisy, low-resolution sensor. But with this sensor they are able to processes information at sufficient speeds to react and respond to unexpected disturbances,' Tonya tells me. 'This is extremely interesting from an engineering perspective because developing technologies that use simpler and fewer electrical sensors and perform equally well can reduce manufacturing costs and computational power.'

Insects also assess changes in their environment using information they receive from other sensory organs on their bodies (including antennae, airflow sensors, and wing-load sensors). Studies have shown that insects pre-process and combine the information from these multiple sensory inputs, prior to reaching the controller. Current robotic technologies, on the other hand, use serial processing systems in which multiple sensors deliver separate and distinct input to the controller. Robot sensors are also currently designed for a very narrow and pre-defined range of conditions.

These limitations impede the response time of today's robots and restrict their ability to maintain or regain stability after unforeseen disturbances. For these reasons, discovering how the efficient parallel processing system seen in insects operates is an area of great interest for engineers developing sensory control systems in robotics.

'Insects might just be the perfect neural information processing model for improving sensory technologies and control systems in electronic applications such as robotics. Yet we are only just beginning to understand the basics of the mechanisms and pathways involved,' Tonya explains. 'We still don’t know how insects extract visual cues from their environment, which cues are the most important, and how those cues are processed to achieve the fast and efficient flight stabilisation that we see,' she says.

By measuring the hawk moth's flight behaviour in response to the visual stimuli presented on the white sphere, Tonya's novel experiments are beginning to shed light on these questions. 'This experimental set-up is really exciting. We can now simulate a 360 degree visual environment for the first time and measure all the forces and moments associated with the moth’s response to a particular stimulus,' she says. 'This is a huge advancement over previous studies that projected visual stimuli in just two dimensions and recorded only a subset of the insects' motion.'

Preliminary results from Tonya's experiments suggest that hawk moths use the angular position and velocity of the projected stripes as a primary cue to stabilise their flight. While describing flight dynamics accurately is an important advancement in the field, it is only the first step towards identifying the mechanisms of the active control of visual feedback in insect flight.

'The next stage of this work will involve measuring the activity of the moths' neurons in response to the visual stimuli presented,' says Tonya. 'These measurements will describe the electrophysiological pathways from the visual sensor to the flight dynamics in this species.'

In the future, Tonya hopes to be able to use implanted electrodes to measure neural activity in the moths. 'The ability to obtain this kind of data remotely from free-flying moths is the cutting-edge of science in this field and a truly exciting prospect,' she says enthusiastically.

Shelly Lachish is a Research Fellow in Oxford's Department of Zoology and a freelance writer.

When dealing with cancer, time is critical. Identifying cancer before it spreads can often be the difference between life and death, so early diagnosis is key.

Cancers begin in one part of the body and often spread through the bloodstream into other organs. This process is known as 'metastasis', and causes secondary tumours, 'metastases', to grow at other locations in the body. These cells which are released from the primary tumour into the bloodstream are called 'circulating tumour cells' (CTCs).

CTCs can be circulating through the bloodstream for years before any metastases form. If small numbers of CTCs can be detected in blood samples, cancers can be diagnosed before they spread. This is no easy task; blood samples might only contain a single CTC among millions of blood cells, and it can be difficult to distinguish between CTCs and normal cells.

'A common signature that a cell in the blood is cancerous is that the CTC has a protein called "EpCAM" on its surface,' says Dr Mark Howarth, a biochemist at the University of Oxford. Dr Howarth develops innovative biological and chemical techniques to image and diagnose cancer, and his group has recently been investigating the use of magnetic beads in cancer diagnosis.

'To catch CTCs, the most common way is to use magnetic attraction,' explains Dr Howarth. 'We use small magnetic beads coated with antibodies. Antibodies are proteins, normally produced by the immune system, which bind to specific targets. By using antibodies which bind only to EpCAM, we ensure that the beads only stick to CTCs. When a magnet is applied, the CTCs move to the magnet and the normal blood cells are washed away.

'We can then study the captured cells in the microscope to understand if the cell really is cancerous. By sequencing the cell’s DNA we can discover other features, such as whether the cancer might be vulnerable to particular drugs. For this reason, even if a person has already been diagnosed with cancer, studying their CTCs could be an important way to make sure that they get the best treatment.'

This technique has great diagnostic potential, as it only requires a standard blood sample from the patient. Yet current methods fail to catch CTCs whose surface contains low levels of markers such as EpCAM. Jayati Jain and Gianluca Veggiani in Dr Howarth's group investigated ways of ensuring that CTCs with fewer surface markers were still picked up by the magnetic beads. This was recently published in the journal Cancer Research.

'We showed that it makes a huge difference to use antibodies with the best binding affinity for their target,' says Dr Howarth. 'For imaging cancer cells, moderate binding affinity is okay, but for isolating cancer cells, there is a force from the magnet pulling the antibody off its target and so only the best antibodies survive.'

The 'binding affinity' between an antibody and its target determines how strongly they are held together. Antibodies with higher binding affinities provide stronger links between CTCs and magnetic beads, so fewer beads will be torn from CTCs when magnetic fields are applied. As a result, more CTCs end up in the final isolated sample.

Another problem with isolating CTCs is that the surface markers which the antibodies must bind to are not simply static.

'Surface markers like EpCAM in the membrane of the cell are moving in a "sea" of lipids and cholesterol,' explains Dr Howarth. 'Cholesterol plays an important role in the physical properties of the cell membrane, affecting its fluidity, elasticity and integrity. We found that the cell’s cholesterol level was crucial to how sensitively the cell could be isolated by the magnetic beads.

'Feeding cells extra cholesterol for an hour meant that even cells with low EpCAM levels were caught. It's worth bearing in mind that all of this is done to blood samples after they have been taken from the patient – we're not talking about pumping people full of cholesterol!'

If enhanced CTC isolation techniques could be rolled out nationwide, cancers could potentially be identified years earlier than they are currently. A recent survey found that around a quarter of cancers in the UK are only diagnosed when the symptoms are so severe that patients are admitted to A&E.

'Using the information we gained about cell isolation, we could capture cancer cells expressing lower levels of distinguishing marker than before,' according to Dr Howarth. 'As the next step we are going on to explore, through collaboration with the Oxford Cancer Research Centre, how our enhanced technique will affect the ability to find CTCs in breast cancer patients and understand the changes happening during the course of the disease. In the long term, we hope that this approach will help searching for CTCs to become a standard tool in looking for early signs of cancer in the most susceptible populations.

'It's worth emphasizing that our modification of this technology has a long way to go before we see it in clinical diagnosis. Clinics in the US already use magnetic isolation techniques, but only to detect cancer recurrence rather than for the initial diagnosis. We need to test our enhanced techniques on the blood samples of real cancer patients to assess their clinical value.

'We must also improve our understanding of CTCs, so that clinicians can reliably identify them under a microscope. With typical current approaches, a few percent of samples give a 'false positive', because some normal cells look like CTCs. In several years, if we could address these issues, CTC isolation could be a powerful and cost-effective tool for primary diagnosis of cancer.'  

One of climate scientists' key ambitions is to predict future climate change more accurately. They create incredibly detailed computer models, but even these cannot calculate all the infinite detail of the real climate.

The inevitable approximations they have to make mean that when it comes to rainfall - one of the most important, yet tricky, aspects of climate - different models seem to say very different things.

But what if, fundamentally, they're not so different? 

What if they all agree that a monsoon will become wetter in future years; it's just that they disagree on the time of year that the monsoon will appear and where exactly it tends to pass over?

'Each model is a bit like a photograph of the same object taken from a slightly different angle,' Adam Levy from Oxford University's Department of Physics tells me. 'If you simply overlaid them they wouldn't match up in many places, but if you can adjust for the different perspectives – of monsoons coming a month or two earlier or later or shifting a bit further south or north - many of the differences between models might just melt away.'

Adam is part of an Oxford University team that recently reported in Geophysical Research Letters a new way of applying techniques used to analyse human brains to climate models. 

In medical imaging, researchers use mathematical techniques to work out the relationships between anatomical regions of the brain that can look different in different patients – something that needs to be adjusted for so that the images 'fit' and they can spot common symptoms or patterns.

In their new approach the Oxford team applied these techniques to 14 of the latest global climate models, first transforming the historical simulations generated by these models so that they lined up better with observations, and then applying these transforms to the models' predictions to see how this affected their agreement on future rainfall. 

To do this, the team have worked in collaboration with medical image analysis researchers in the Oxford Centre for Functional MRI of the Brain (FMRIB).

'Climate models seem to disagree about rainfall quite a lot, which is a huge problem, as changes in rainfall will have bigger human impact than many other aspects of climate change. What we found, though, was that when we transformed the models using our technique we had managed to iron out a substantial part of the disagreement,' Adam explains.

The transformation increased agreement between the models by an average of 15%, although some areas saw more benefits than others. Overall there was increased agreement across 66% of the globe about rainfall patterns. This first test run used an extreme climate scenario in which unabated carbon dioxide emissions have quadrupled atmospheric levels. However, the plan is to apply the technique to more realistic and subtle simulated scenarios.

The team are currently working on dedicated software which takes into account the many ways that climate models differ from brains - for instance in being wrapped around a sphere as opposed to a 3D 'image' of a subject's brain - to create tools tailored to this new application.

'The long-term goal is to be able to make accurate predictions of how climate change will affect average rainfall at a given time, at a given location on the globe,' says Adam.

Such techniques could give us a much clearer picture of what climate models are really saying about how rainfall patterns are likely to change – and this could help to ease the strain on the brains of policy makers trying to plan for our planet's future.  

The atomic structure of a zinc-based material has a surprising amount in common with the tentacles of an octopus, Oxford University researchers have found.

When pressure is applied all around them most materials shrink. But materials exhibiting a rare property known as negative linear compressibility (NLC) are different.

'When pressure is applied all around NLC materials, instead of their dimensions getting shorter, they reduce their volume by getting longer,' Andrew Goodwin of Oxford University's Department of Chemistry tells me, 'think of it a bit like one of those collapsible wine racks.'

Andrew and his Oxford colleagues led an international team studying the unusual thermal properties of the material zinc dicyanoaurate. What they did not expect to find was that its honeycomb-like structure gave it uniquely powerful NLC behaviour, far beyond the kind of contraction and expansion exhibited by ordinary engineering materials.

A report of their research is published in Nature Materials.

There's widespread interest in NLC because of how materials with these properties could be used in artificial muscles or new types of sensors.

'It was quite surprising to discover that zinc dicyanoaurate is made up of structures that act rather like sets of supramolecular springs that cause it to behave in this way,' says Andrew. 'What's particularly exciting is that these properties scale up from the atomic scale to that of manmade objects and structures, suggesting all sorts of possible applications.'

Often scientists take inspiration from biological systems, or even try to copy them, but in this case the discovery of atomic structures could make them look afresh at biology.

'It seems that the octopus has found a way of harnessing the same intrinsic properties we've found in zinc dicyanoaurate,' Andrew explains. 'When it wants to contract a particular limb an octopus squirts liquid into the centre of a helical chamber inside the tentacle. This creates the equivalent of negative pressure on the tentacle, causing it to get fatter in cross section and, through the muscle architecture, contract in length.

'These same geometrical motifs found in materials at the atomic scale can also be found around us in the Animal Kingdom.'

The first to benefit from zinc dicyanoaurate's NLC properties could be the construction industry: including an ingredient like it in cement, that 'pushes back' when other components swell due to the presence of water, could help to prevent cracking in structures.

Other likely applications include the optical world where it could be used to create adjustable lenses or sensors that respond to pressure in a different way from those made of conventional materials.

Could it one day be used to make the sort of artificial tentacles sported by Spider-Man's nemesis Doc Ock? That's one application that may have to wait.

A report of the research, entitled 'Giant negative linear compressibility in zinc dicyanoaurate', is published in this week's Nature Materials.

The Oxford authors are: Andrew Goodwin, Andrew Cairns, and Amber Thompson.

At some point – whether it's at the doctors, at the gym, or online – all of us have probably encountered the Body Mass Index.

Body Mass Index (BMI) is derived from a simple mathematical formula, devised by Belgian scientist Adolphe Quetelet in the 1830s, that divides a person's weight in kilograms by their height in metres squared to arrive at an estimate of an individual's body fat.

It's supposed to provide an approximate measure to help judge if someone has a healthy weight – and indicate, for instance, if they are obese. But as Nick Trefethen of Oxford University's Mathematical Institute pointed out in a recent letter to The Economist the basic formula BMI relies on is flawed:

'If all three dimensions of a human being scaled equally as they grew, then a formula of the form weight/height³ would be appropriate. They don't! However, weight/height² is not realistic either,' Nick tells me.

'A better approximation to a complex reality, which is the reform I wish could be adopted, would be weight/height^2.5. Certainly if you plot typical weights of people against their heights, the result comes out closer to height^2.5 than height².'

Sticking with the current formula, he says, leads to confusion and misinformation: 'Because of that height² term, the BMI divides the weight by too large a number for short people and too small a number for tall people. So short people are misled into thinking they are thinner than they are, and tall people are misled into thinking they are fatter than they are.'

Quetelet's formula was invented at time when there were no calculators or computers so it's perhaps little wonder he opted for something so simple. What's stranger, perhaps, is why institutions such as the NHS, the Department of Health, and the National Obesity Observatory continue to use the same flawed formula today.

The reason for its survival may be that all the various agencies have agreed on it and, Nick says, 'nobody wants to rock the boat.'

It highlights, perhaps, how uncritical many of us are of the mathematics behind widely-used measures. There are probably many more flawed formulas out there but as Nick comments 'it would be hard to compete with this one in impact in a world approaching a billion obese people!'

So what's the alternative and what difference would changing the formula make to the medical measure of BMI?

Nick proposes a new formula [more detail here] where BMI = 1.3*weight(kg)/height(m)^2.5 = 5734*weight(lb)/height(in)^2.5

'Suppose we changed that exponent from 2.0 to 2.5 and adjusted the constant so that an average-height person did not change in BMI. Suddenly millions of people of height around 5' would gain a point in their readings, and millions of people of height around 6' would lose a point,' Nick explains. 

'In our overweight world, such changes would distress some short people and please some tall people, but the number they'd be using would be closer to the truth and good information must surely be good for health in the long run.'

Intriguingly, it's likely that Quetelet would have approved of using the 2.5 exponent. Alain Goriely, also of Oxford University's Mathematical Institute, says that Quetelet himself was well aware of the wrong choice of scaling.

In 1842 Quetelet wrote in 'A Treatise on Man and the Development of his Faculties':

'If man increased equally in all dimensions, his weight at different ages would be as the cube of his height. Now, this is not what we really observe. The increase of weight is slower, except during the first year after birth; then the proportion we have just pointed out is pretty regularly observed.

'But after this period, and until near the age of puberty, weight increases nearly as the square of the height. The development of weight again becomes very rapid at puberty, and almost stops after the twenty-fifth year. In general, we do not err much when we assume that during development the squares of the weight at different ages are as the fifth powers of the height; which naturally leads to this conclusion, in supporting the specific gravity constant, that the transverse growth of man is less than the vertical.'

Alain comments: 'So according to Quetelet the scaling is 3 for babies (babies are spheres), 2 for kids (kids grow more like celery sticks, as we know), then 5/2=2.5 for grownups (beefing up so to speak). It seems Quetelet never cared about obesity (not a big issue in the 1840's).'

Nick Trefethen is Professor of Numerical Analysis at the University of Oxford.

Alain Goriely is Professor of Mathematical Modelling at the University of Oxford.