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Physicists identify most complex protein knots

Scientists in Germany and the US have predicted the most topologically complex knot ever found in a protein using AlphaFold, the artificial intelligence (AI) system developed by Google’s DeepMind. Their complete analysis of the data produced by AlphaFold also revealed the first composite knots in proteins: topological structures containing two separate knots on the same string. If the discovered protein knots can be recreated experimentally it will serve to verify the accuracy of predictions made by AlphaFold.

Proteins can fold to form complex topological structures. The most intriguing of these are protein knots – shapes that would not disentangle if the protein were pulled from both ends. Peter Virnau, a theoretical physicist at Johannes Gutenberg University Mainz, tells Physics World that there are currently around 20 to 30 known knotted proteins. These structures, Virnau explains, raise interesting questions around how they fold and why they exist.

A protein’s shape can be closely linked with its function, but while there are a few theories on the functionality and purpose of protein knots there is little hard evidence to back these up. Virnau says that they might help to keep the proteins stable, by being particularly resistant to thermal fluctuations, for instance, but these are open questions. While protein knots are rare, they also appear to be highly preserved by evolution.

“If a knotted protein exists, for example, in yeast, there is a high likelihood that it is also knotted in the corresponding protein in humans,” Virnau explains. “So, these are structures that have been around for hundreds of millions of years.”

A long-standing problem in protein knot research has been finding and identifying protein knots. While complex protein structures have been experimentally determined in the laboratory, this can be challenging and time consuming. Recently, DeepMind developed an AI system known as AlphaFold that it claims can predict protein structures with incredible speed and precision. The deep-learning system works on a large database of known proteins and their amino acid sequences. It uses those sequences and information on the primary structure of amino acids to predict the three-dimensional structures of the proteins. Its training is based around evolutionary, physical and geometric constraints of protein structures.

AlphaFold has predicted several hundred thousand protein structures, most of which have not yet been catalogued. In this latest work, published in Protein Science, Virnau and his colleagues searched AlphaFold’s databank for previously unknown complex protein knots. They discovered nine new knots. This included the first 71-knot – a knot with seven crossing points that is the most topologically complex knot ever found in a protein.

The researchers also found several six-crossing composite knots. These each contain two trefoil knots, which are knots with three crossings. They also discovered two previously unknown knots with five essential crossings, a 51-knot and a 52-knot.

The team is now working with biochemist Todd Yeates, at the University of California Los Angeles, to create the proteins identified by AlphaFold experimentally to confirm that they form the predicted topological structures. “I’m quite confident that we will be able to confirm these structures experimentally,” says Virnau.

If these topologically challenging structures can be created experimentally it would show that AlphaFold is working as expected and provide confidence in its predictions of less complex protein shapes. “The protein knots might only be a minor aspect of this, but it may nevertheless serve as a validation of these tools in general,” Virnau explains.

In the future it might be possible to use these AI tools for protein engineering. Proteins could be designed containing knots and other complex structures that provide them with functionality for specific tasks, although this is at least a few years away.

Building a science centre that will inspire local communities, musing over first lines in science books

Many physicists are keen to share their enthusiasm for science with the public, and this often involves participating in events at different venues across a community. In this episode of the Physics World Weekly podcast, we meet four people in the Canadian city of Guelph who believe that their community’s appetite for science is so great that it warrants a dedicated science centre.

All four are all members of Royal City Science, which was founded in 2020 with the aim of building a science centre in Guelph. They are Joanne O’Meara and Orbax, both physicists at the University of Guelph; Kate Howells of the Planetary Society; and the business executive George Staikos.

The Guelph quartet talk about their outreach activities – including a popular series of activities at local breweries – and about the challenges of raising awareness and funding for their ambitious project.

Also in this week’s episode, Physics World’s Sarah Tesh and Matin Durrani talk about our latest quiz, which looks at the opening lines of famous physics-related popular science books. You can take the quiz at “The first-sentence challenge”.

Device-independent QKD brings unhackable quantum Internet closer

Two independent research groups have demonstrated a protocol for distributing quantum-encrypted keys via a method that is sure to leave would-be network hackers in the dark. The protocol, dubbed device independent quantum key distribution, was first proposed three decades ago but had not been realized experimentally before due to technical limitations, which the researchers have now overcome.

Most people use encryption regularly to ensure that information they transfer via the Internet (such as credit card details) does not fall into the wrong hands. The mathematical foundations of present-day encryption are robust enough that the encrypted “keys” cannot be cracked, even with the fastest supercomputers. This classical encryption may, however, be at risk from future quantum computers.

One solution to this problem is quantum key distribution (QKD), which uses the quantum properties of photons, rather than mathematical algorithms, as the basis for encryption. For example, if a sender uses entangled photons to transmit a key to a receiver, any hacker who tries to spy on this communication will be easy to detect because their intervention will disturb the entanglement. QKD therefore allows the two parties to generate secure, secret keys that they can use to share information.

Vulnerable devices

But there’s a catch. Even if information is sent in a secure way, someone could still gain knowledge of the key by hacking the devices of the sender and/or receiver. Because QKD generally assumes that devices maintain perfect calibration, any deviations can be difficult to detect, leaving them prone to being compromised.

An alternative is device independent QKD (DIQKD), which as its name implies operates independently of the state of the device. DIQKD works as follows. Two users, traditionally named Alice and Bob, each possess one particle of an entangled pair. They measure the particles independently using a strict set of experimental conditions. These measurements are divided into those that are used to generate a key for encryption and those that are used to confirm entanglement. If the particles are entangled, the measured values will violate conditions known as Bell’s inequalities. Establishing this violation guarantees that the key-generation process has not been tampered with.

Schematic diagram showing a photo of John Stewart Bell being encrypted at Alice's end, transmitted securely, and then decrypted at the Bob node to reconstitute the image..

High-fidelity entanglement, low bit error rate

In the new research, which is described in Nature, an international team from the University of Oxford (UK), CEA (France) and the EPFL, the University of Geneva and ETH (all in Switzerland) performed their measurements on a pair of trapped strontium-88 ions spaced two metres apart. When these ions are excited to a higher electronic state, they spontaneously decay, emitting a photon apiece. A Bell-state measurement (BSM) is then performed on both photons to entangle the ions. To ensure all information is kept within the setup, the ions are then guided to a different location where they are used to perform the DIQKD measurement protocol. After this the sequence is repeated.

Over a period of nearly eight hours, the team created 1.5 million entangled Bell pairs and used them to generate a shared key 95 884 bits long. This was possible because the fidelity of the entanglement was high, at 96%, while the quantum bit error rate was low, at 1.44%. The Bell inequality measurements, meanwhile, produced a value of 2.64, well above the classical limit of 2, meaning the entanglement was not hampered.

In a separate experiment, also described in Nature, researchers at Germany’s Ludwig-Maximilian University (LMU) and the National University of Singapore (NUS) used a pair of optically trapped rubidium-87 atoms located in laboratories 400 metres apart and connected by a 700-metre-long optical fibre. Similar to the other team’s protocol, the atoms are excited and the photons they emit as they decay back to their ground state are used to perform a BSM that entangles the two atoms. The atom’ states are then measured by ionizing them to a particular state. Since ionized atoms are lost from the trap, a fluorescence measurement to check for the presence of the atom completes the protocol.

The LMU-NUS team repeated this sequence 3 342 times over a measurement period of 75 hours, maintaining an entanglement fidelity of 89.2% and a quantum bit error rate of 7.8% throughout. The Bell inequality measurement yielded a result of 2.57, again proving the entanglement remained intact over the measurement period.

Now make it practical

For DIQKD to become a practical encryption method, both teams agree that key generation rates will need to increase. So, too will the distances between Alice and Bob. One way of optimizing the system might be to use cavities to improve photon collection rates. Another step would be to parallelize the entanglement generation process by using arrays of single atoms/ions, rather than pairs. In addition, both teams generate photons at wavelengths with high losses inside optical fibres: 422 nm for strontium and 780 nm for rubidium. This could be addressed through quantum frequency conversion, which shifts photons into the near-infrared region where optical fibres used for telecommunication exhibit much lower loss.

Tim van Leent, a PhD student at LMU and a co-lead author of the LMU-NUS paper, notes that the keys the Oxford-CEA-Switzerland team generated were secure under so-called finite-key security assumptions, which he calls “a great achievement”. He adds that the other team’s work on implementing all necessary steps in the QKD protocol sets an important precedent, pointing out that the entanglement quality reported in this experiment is the highest so far between distant matter-based quantum memories.

Nicolas Sangouard, a physicist at CEA who is one of the lead investigators of the project, says that the LMU-NUS researchers succeeded in showing that entangled states can be distributed over hundreds of metres with a quality that is, in principle, high enough to perform device-independent quantum key distribution. He adds that the difficulties they had to overcome serve as a good illustration of the challenges that device-independent QKD still poses for quantum networking platforms. Extracting a key from the raw data remains particularly difficult, he adds, as the number of experimental repetitions is not enough to extract a key from the measurement results.

Excitonic insulators are created in moiré superlattices

Excitonic insulators – an exotic type of matter with a ground state comprising bound electron–hole pairs – have been made by two independent research groups. The excitonic insulators were created in layered materials called van der Waals heterostructures and the research could potentially lead to the discovery of new quantum phases of matter such as excitonic superfluids. Excitonic insulators could also have practical engineering applications.

Excitons are normally formed in an insulator or semiconductor when an electron is promoted to a higher energy band (by a photon, for example), leaving behind a positively charged “hole”. The electron and hole bind together to create an exciton that behaves much like a particle, which is why excitons are classified as quasiparticles.

Back in the 1960s, the British theoretical physicist and future Nobel laureate Nevill Mott reasoned that, if the band structure of a material were tuned such that, at certain points, the upper energy level is below the lower energy level, then the ground state of the system would contain excitons. Electrons and holes would remain bound together by the Coulomb interaction, but it would be energetically unfavourable for them to recombine. As the excitons would be neutrally charged, they would not carry an electric current and the resulting material would be an insulator.

This remained purely hypothetical until last year, when two groups – one led by Sanfeng Wu and colleagues at Princeton University in New Jersey, the other by David Cobden’s group at the University of Washington in Seattle – independently found evidence suggesting that monolayer tungsten ditelluride showed features consistent with an excitonic insulating state at temperatures below 100 K.

Moiré superlattices

In new research, two independent teams – one led by researchers at University of California, Berkeley; the other a collaboration between scientists in the US, China and Japan – have taken similar, three-layer approaches to creating excitonic insulators. Both groups used heterostructures in which the top two layers formed a moiré bilayer. These bilayers are created when multiple monolayers – here tungsten disulfide and tungsten diselenide – are twisted relative to one another. This creates “superlattices” as the individual lattices move in and out of phase. Such materials have a periodic band structure, which can allow them to form another type of exotic correlated insulator called a Mott insulator in which electrons are confined by this periodicity.

Both groups also used a monolayer of tungsten diselenide as the bottom layer. The Berkeley-led researchers insulated the moiré bilayer from the monolayer using an atomically-thin layer of hexagonal boron nitride. They applied a variable potential across the heterostructure, changing which layer was electron doped and which layer was hole doped. Using optical reflectance spectroscopy, the researchers observed electrons in one layer binding to holes in the other at temperatures below 60 K. “When you dope the moiré bilayer with holes, you get a hole at each lattice site,” explains Berkeley’s Zuocheng Zhang. “If we electron-dope the Mott insulator, the holes will generally be gone. But the holes in the monolayer tend to stay above the part that does not have a hole to minimize the very strong Coulomb interaction.”

The US–China–Japan team performed similar experiments, using an applied electric field to tune the energy levels of the two adjacent layers of tungsten diselenide to create interlayer excitons. They did not use a hexagonal boron nitride layer, however. “These two materials are naturally separated by a van der Waals gap, which is insulating,” says team member Sufei Shi of Rensselaer Polytechnic Institute in New York. “If you have boron nitride in between, that’s going to increase the spatial separation, but it’s going to decrease the Coulomb interaction.” The benefits of this trade-off, the researchers believe, may be evident in their higher transition temperature of 90 K.

Neutral bosons

Both teams now aim to use their platforms to further study the properties of excitonic insulators – which they believe could be markedly different from those of other exotic insulators such as Mott insulators. “In Mott insulators, everything is electrons, so they’re still fermions,” says Yongtao Cui of University of California, Riverside – who is a member of the US–China–Japan team. “In the excitonic insulator, the fundamental units are bound states of electrons and holes, which are charge neutral, and they’re bosons.” This could potentially lead to exotic states of matter such as excitonic superfluids. Fellow team member Chuanwei Zhang of the University of Texas at Dallas says that several obstacles remain, such as increasing the density of the excitations and reducing their temperature, making them delocalized enough to reach quantum degeneracy. The Berkeley researchers also plan to study exciton superfluidity.

“I think these are beautiful, important [studies],” says Wu. “The theoretical idea was half a century ago, and we are still at the stage of trying to conclusively find [excitonic insulators], and with excitonic insulators there are many different types.” He says researchers need to develop more unambiguous detection techniques. Moreover, he believes the current work could find engineering applications in “excitonics”. This aims to create devices that use excitons to transfer information without the heat loss associated with charge transfer. However, practical excitonics has been limited by the short lifetime of optically excited excitons. Wu points out that the latest work offers a way around this problem, “Compared to all known excitons in semiconductors, these excitons in ground states can live for a very long time,” he says. “If you could make them flow, you could make functional devices without charge.”

The research is described in two papers Nature Physics. One paper is by the Berkeley-led team and the other paper is by the US–China–Japan team.

Magnets, magnets, magnets: we’ll need lots of them for a green economy

I was recently in Newcastle to attend PEMD2022 – the 11th international conference on power electronics, machines and drives. What struck me was not only the huge performance improvements that have been happening in electric motors and generators but just how far we still have to go to make transport fully carbon-free.

Global sales of electric cars (including fully battery powered, fuel cell and plug-in hybrids) doubled in 2021 to an all-time high of 6.6 million. They now account for 5–6% of vehicle sales, with more being sold each week than in the whole of 2012, according to the Global Electric Vehicle Outlook 2022 report.

Each new electric vehicle will need at least one high-power electric motor

Projections vary, but annual sales are expected to increase to 65 million electric vehicles by 2030 globally, according to market research firm IHS Markit. Annual sales of vehicles with internal combustion engines, in contrast, will decline from 68 million units in 2021 to 38 million by 2030.

What’s obvious is that each new electric vehicle will need at least one high-power electric motor. Almost all (about 85%) of these vehicles currently use motors with permanent magnet (PMs) as they are the most efficient (the record is 98.8%). A few use Alternating Current (AC) induction motors and generators, but they are 4–8% less efficient than PM motors, up to 60% heavier and up to 70% larger.

Still, these non-PM motors and generators are perfect for, say, trucks, ships and wind-turbine generators. They are also easy to recycle as they can, in principle, be made of one material (say aluminium) and then melted down when they come to the end of their life. Some firms, like Tesla Motors, are even combining the PM and electromagnetic approaches in ever more complex designs to optimize performance and range. None of the advances in electric vehicles would, however, be possible without the huge advances in solid-state power electronics.

Magnetic attraction

Magnets have come a long way since a shepherd in Magnesia in northern Greece noticed the nails in his shoe and the metal tip of his staff were stuck fast to a magnetic rock (or so legend has it). These “lodestones” were used for thousands of years in compasses to navigate but it was not until the early 1800s that Hans Christian Ørsted discovered that an electric current can influence a compass needle.

The first demonstration of a motor with rotary motion occurred in 1821 when Michael Faraday dipped a free-hanging wire into a pool of mercury, on which a PM was placed. The first DC electric motor that could turn machinery was developed by British scientist William Sturgeon in 1832. US inventors Thomas and Emily Davenport built the first practical battery-powered DC electric motor at about the same time.

These motors were used to run machine tools and a printing press. But as the battery power was so expensive, the motors were commercially unsuccessful, and the Davenports ended up bankrupt. Other inventors who tried to develop battery-powered DC motors struggled with the cost of the power source too. Eventually, in the 1880s, attention turned to AC motors, which took advantage of the fact that AC can be sent over long distances at high voltage.

The first AC “induction motor” was invented by the Italian physicist Galileo Ferraris in 1885, with the electric current to drive the motor obtained by electromagnetic induction from the magnetic field of the stator winding. The beauty of this device is that it can be made without any electrical connections to the rotor – a commercial opportunity seized upon by Nikola Tesla. Having independently invented his own induction motor in 1887, he patented the AC motor the following year.

For many years, though, PMs had fields no higher than naturally occurring magnetite (about 0.005 T). It wasn’t until the development of alnico (alloys of mostly aluminium, nickel and cobalt) in the 1930s that practically useful PM DC motors and generators became a possibility. In the 1950s low-cost, ferrite (ceramic) PMs appeared, followed in the 1960s by samarium and cobalt magnets, which were stronger again.

But the real game-changer occurred in the 1980s with the invention of neodymium PMs, which contain neodymium, iron and boron. These days, the N42 grade of neodymium PMs has a strength of some 1.3 T, although that’s not the only key metric when it comes to magnet and motor design: operating temperature is vital too.

Prices of some rare-earth materials have skyrocketed, prompting a huge amount of research into new magnet compositions

That’s because the performance of PMs falls as they warm-up and once they go above “Curie point” (about 320 °C for neodymium magnets), they completely demagnetize – rendering the motor useless. Another important thing about all rare-earth magnets, including neodymium, cobalt and samarium, is that they have a high coercivity, meaning they don’t demagnetize easily when in operation. To make the highest coercivity and best temperature performance magnets you also need small amounts of other heavy rare earths such as dysprosium, terbium and praseodymium.

A question of supply

Trouble is, rare-earth elements are in short supply. It’s not because they are intrinsically rare, their name simply comes from their location in the periodic table. According to a report last year from Magnetics & Materials LLC, by 2030 the world will need 55,000 more tonnes of neodymium magnets than are likely to be available, with 40% of the total demand expected to come from electric vehicles and 11% from wind turbines.

China currently makes 90% of all the world’s neodymium magnets, which is why the US, the EU and others are all trying to develop their capabilities in the supply chain so as not to be disadvantaged. Prices of some rare-earth materials have skyrocketed, prompting a huge amount of research into new magnet compositions, recycling of existing magnets and advanced AC induction motors.

Whichever way you look at it, we’re going to need a lot of magnets if we are to green the economy.

Light restores charge to slippery surfaces

A super-slippery material that can efficiently generate surface charges when illuminated could pave the way for next-generation interfacial materials and microfluidics. The new material is a combination of a copolymer, tiny liquid metal particles and lubricant-trapping microstructures, and its developers say it could find applications in lab-on-a-chip devices, biological diagnostics and chemical analysis.

Slippery lubricant-infused porous surfaces (SLIPS) show much promise for devices that are self-cleaning, anti-icing and able to resist “fouling” by microorganisms that might otherwise accumulate on structures such as boat hulls or microfluidic chips. Such lubricants do have their downside, however. For one, they act as a physical screen for the material beneath them, thereby masking any desirable properties (such as surface charge) it might have. Such screening is not good for applications in which droplets and liquids need to be manipulated and transported across the slippery surface in a controlled way.

Robust charge regeneration capability

Researchers led by Xuemin Du of the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, have now developed a slippery material that does not suffer from these screening effects. The new light-induced charged slippery surface (LICS), as it is called, consists of three core components: micro-sized Ga-In liquid metal particles for efficiently converting absorbed light into local heat; poly(vinylidene fluoride-co-trifluoroethylene) copolymer for its excellent ferroelectric behaviour; and microstructures coated with a layer of hydrophobized SiO2nanoparticles for trapping the lubricant.

In a series of experiments detailed in Science Advances, the team used light to control the movement of droplets placed on the new LICS, moving them at speeds as high as around 18.8 mm/s and over distances as long as around 100 mm. These droplets, which can be either microscopic or macroscopic (their volumes ranged from 10-3 to 1.5 x 103 µL) can also climb up flat or curved surfaces thanks to the charge on the LCIS – something that is not possible for current SLIPS.

“The LICS can rapidly reach as high as 1280 pico-Coulombs per square mm in 0.5 s when exposed to light illumination,” Du explains. “Its robust charge regeneration capability shows no apparent decay even after being exposed to 10 000 cycles of impulse near-infrared irradiation, or even immersed in silicone oil for six months.”

According to the team, the LICS could be used to create steerable droplet-based robots and for performing chemical reactions. It could also be integrated into a pump-free microfluidic chip, allowing for reliable biological diagnosis and analysis in a closed design.

The researchers now plan to further optimize their control of the droplets. “We will also be expanding the biochemical applications of these intelligent polymers and LICS microfluidic chips,” Du tells Physics World.

Colourful nanotubes become flame-resistant

coloured nanotubes

“Structurally colouring” carbon nanotubes with an amorphous layer of titanium dioxide not only makes them easier on the eye, it also makes them flame-resistant. This is the finding of researchers from Tsinghua University in Beijing, China, who say that these new properties should make it easier to employ nanotubes in wearable devices, smart textiles and functional coatings.

Carbon nanotubes (CNTs) are rolled-up sheets of carbon one atom thick. Thanks to their excellent electrical and mechanical properties, they show promise for many applications, including ultra-strong fibres and conductive wires. They do, however, have two inherent shortcomings: they are jet black in colour, which makes them aesthetically unattractive for some applications; and they are flammable, which means they cannot be employed in high-temperature environments where oxygen is present.

Colour control

Researchers led by Rufan Zhang of Tsinghua University’s Department of Chemical Engineering have now coated CNTs with amorphous TiO2 layers using a technique called atomic layer deposition (ALD). They report that this technique worked for both CNT fibres and CNT membranes and that they could control the colour by tuning the thickness of the coatings.

The team found that as well as increasing the structural and functional diversity of the CNTS, the coating process also makes them resistant to flames. Indeed, the materials can withstand eight hours of burning – unlike ordinary CNTs, which burn easily.

Chemically stable

Compared with conventional dyes and pigments, which are chemically unstable and cannot be used for colouring CNTs, the TiO2 coating-based structural colours can endure 2000 cycles of laundering, Zhang says, and more than 10 months of exposure to high-intensity ultraviolet irradiation.

The technique is convenient, simple, easily repeatable and easy to scale up, he adds. It produces brilliant, controllable colours, such as indigo, yellow-brown, blue, purple and green. Importantly, it does not affect the intrinsic electrical and mechanical properties of the CNTs.

The TiO2-coated CNTs might be used in numerous cutting-edge applications, Zhang tells Physics World. “These include ultra-strong fibres, wearable devices, smart textiles and devices that operate in high-temperature environments (such as aircraft, missiles and rockets), optical displays, colorimetric sensors, anti-counterfeiting devices, information encryption, multicolour passive photonic displays, optical fibres and lasers, to name just a few.”

The researchers now aim to further expand the colour range of their CNTs. “We will also further investigate the excellent performance of the coloured CNTs and look into interdisciplinary applications,” Zhang says.

The work is described in Science Advances.

Optoacoustic imaging identifies breast cancer from vascular patterns

OA-US images

Adding optoacoustic (OA) imaging to ultrasound (US) could improve the diagnosis of breast cancer, according to findings from a multidisciplinary research team in Cambridge, UK. The combination enables visualization of functional blood vasculature overlaid with structural features of the breast.

To help accelerate the clinical application of this combined technique, the team developed a simple feature set using single-wavelength OA data from an integrated OA-US imaging system that can identify malignant breast lesions based on their vascular patterns. The researchers describe their findings in Photoacoustics.

A low-cost OA-US device using this feature set could increase the number of early breast cancer diagnoses, especially in women living in low-income countries, where breast cancer survival rates are less than 40% (compared with 80% in high-income countries). The proposed device could also expand breast cancer screening in populations with limited access to mammography.

Ultrasound imaging alone tends to have low sensitivity for breast cancer detection, and cannot always differentiate between benign and malignant lesions. OA imaging – a potentially low-cost technique based on optical excitation and acoustic detection – is being evaluated in clinical studies for breast cancer diagnosis, but the current analysis process is quite complex.

Sarah Bohndiek

Principal investigator Sarah Bohndiek, of the University of Cambridge’s Cancer Research UK Cambridge Institute and department of physics, explains that the researchers’ objective was to simplify acquisition of OA-US data and create a simple imaging feature set that was easy to learn and clinically feasible to implement.

The team generated the feature set using images from 96 breast lesions in 94 patients with benign, indeterminate or suspicious breast abnormalities at Cambridge University Hospitals NHS Foundation Trust. The first 38 lesions (including 14 malignant and eight benign) were used to develop the feature set; the others were used for validation.

All patients in the study underwent mammography, breast ultrasound and OA imaging – performed using an OA device that also incorporated low-frequency tomographic ultrasound. The researchers used an excitation wavelength of 800 nm, which minimizes absorption by water and lipids, to create images showing the morphology of blood vessels surrounding a solid breast lesion. The use of a single wavelength simplified OA image processing and visualization, offering the possibility of future system simplification and cost reduction.

The researchers analysed the OA and US images separately and in combination, looking for patterns of blood vessels representative of healthy breast tissue, benign disease and malignancy. Benign lesions demonstrated no vascularity or vessels that were draped over the lesion without penetrating it. Malignant lesions had irregular feeding vessels that penetrated into the lesion and/or a disorganized irregular pattern around them. The internal appearance of the lesions did not differentiate benign and malignant lesions and was not used.

The researchers selected three features of malignancy that would upgrade any solid lesion to a BI-RADS 5 classification (highly suggestive of malignancy): irregular cap, irregular feeding vessel and claw sign. The presence of benign features – no vessels or vessels splayed over the lesion vessel – would downgrade a lesion to BI-RADS 2 (benign).

Two breast radiologists validated the feature set by independently interpreting the OA-US validation images (31 malignant and 13 benign solid lesions). It took only 20 min of training for them to become proficient in using the feature set. They were asked to use the features to classify lesions by BI-RADS category, as well as to classify the patients’ diagnostic ultrasound exams and mammography images.

The breast radiologists interpreted the OA-US images with a sensitivity of 96.8% and a specificity of 84.6%, with one false negative and two false positives for each reader. In comparison, mammography yielded three false negatives and two false positives for each reader, and ultrasound generated one false negative and six and seven false positives. Importantly, all of the mammography and ultrasound false negatives were correctly identified as positive by OA.

Bohndiek points out that OA-US requires practical experience to optimize the standard operating procedure and obtain high-quality image data, and for this reason, future multicentre validation studies should consider operator dependence and independent calibration.

“We have been undertaking validation studies of the OA-US device in the context of developing stable test objects (phantoms) that can be used by medical physicists for QA/QC once the devices are used routinely in the clinic,” she tells Physics World. “We are also planning to apply the system in the future to monitoring of response to radiotherapy treatment in breast cancer.”

Unexpected phase transition appears in elemental neodymium

Usually, when materials heat up, they become more disordered. Now, researchers at Radboud University in the Netherlands have found evidence for the opposite happening in the element neodymium, which develops long-range order as its temperature increases. The presence of this phase transition could shed light on the behaviour of materials known as spin glasses and could also aid the development of devices for information storage or neuromorphic computing.

Spin glasses such as neodymium (Nd) are a special class of magnetic materials in which particle spins form random, helix-like patterns below a certain critical temperature (termed the spin glass temperature). They are often considered to be disordered magnets and are different from other such “frustrated” magnets such as spin ices and spin liquids.

Recently, researchers led by Alexander Khajetoorians at Radboud discovered that Nd is a self-induced spin glass – meaning that the spin glass state comes about thanks to competing spin-exchange interactions that arise from the material’s own lattice structure. These interactions mean that Nd can exist in multiple low-energy states defined by its reciprocal lattice vector (or magnetic wavevector) Q.

Spins “freeze” into a solid

In the latest study, Khajetoorians and his colleagues observed the spins “freeze” into a solid as they heated the element from -268 °C to -265 °C. When they cooled it down again, the random spin whirling patterns reappeared.

Khajetoorians notes that the appearance of this disorder-order transition in Nd defies the common perception that increasing temperature induces disorder. Such a transition does not normally occur in magnetic materials, he adds, and it is also uncommon in other materials. One exception is Rochelle salt, which contains charges that are randomly distributed at lower temperatures, but build up and form an ordered pattern as the temperature increases.

In Nd, the behaviour is linked to a phenomenon in which many different states have the same energy, causing the system to become frustrated, the researchers say. An increase in temperature lifts the frustration with one ordering tendency surviving, allowing the spins to settle into an ordered pattern over a long range. “Specifically, the new state is a so-called multi-Q one,” Khajetoorians tells Physics World. “There is a high-energy phase at low temperature and vice versa.”

Applications in information storage and neuromorphic computing

The Radboud team used spin-polarized scanning tunnelling microscopy (STM) to probe the magnetic texture on the surface of Nd. They developed two analysis tools that allowed them to extract the spin glass transition temperature directly from their measured data at different temperatures. They observed many different and smoothly varying patterns in the element at 5 K (-268 °C) and fewer patterns at higher temperatures that were clearly separated by magnetic domain walls.

The researchers also compared their observations with atomistic spin dynamics simulations to help them trace the origins of the unexpected high-temperature order.

Khajetoorians says that he and his team will now be studying what happens when Nd is made thinner since this might induce some further unexpected effects. They would also like to test other magnetic materials to see if they exhibit the same spin-glass behaviour, which they say could be harnessed for new types of information storage or to develop neuromorphic computers.

The work is detailed in Nature Physics.

The unique universe of Satyajit Ray

Satyajit Ray, sitting behind the camera operator, on set

Picture a scenic pond nestled within the confines of a small village in Bengal, its calm surface dotted with lotus flowers. Then imagine, one moonlit night, a spaceship splashing down and sinking into its depths, until the only thing visible is a golden spire sticking out of the water. The local villagers think it is a temple risen from the Earth below. Most of them decide to worship it. Little do they realize that the object contains a small humanoid creature that will invisibly play havoc in their lives.

If you think this sounds like an entertaining idea for a science-fiction film, you would be right. And if perhaps, you were to think it somewhat similar to the famous 1982 film E.T. the Extra-Terrestrial, directed by Steven Spielberg, you might not be far off either. But this other alien, the one that crash-landed in India and not America, never quite made it to movie screens across the globe, despite being dreamed up in the 1960s by one of the most significant film directors of the 20th century – Satyajit Ray.

Universal appeal

Born in Calcutta (Kolkata) in 1921, the Bengali polymath was not only a film director but also an established author, essayist, magazine editor, illustrator, calligrapher and music composer. Although all of his films are set in India, the finest of them hold worldwide appeal. Between 1955 and 1991, Ray directed almost 30 features, as well as short films and documentaries. Many won leading prizes at international film festivals. In 1991 he was awarded an Oscar for lifetime achievement – the only such Oscar to be bestowed on an Indian director. Ray also received an honorary doctorate from the University of Oxford: the second film director to be awarded this honour after his hero Charles Chaplin.

Not to have seen the cinema of Ray means existing in the world without seeing the Sun or the Moon

Akira Kurosawa

“Not to have seen the cinema of Ray means existing in the world without seeing the Sun or the Moon”, said Japan’s iconic film director, Akira Kurosawa, in 1975. On Ray’s 70th birthday in 1991, British film director Richard Attenborough, who had acted superbly on screen for Ray, called him a “rare genius”. And in 2021, on the centenary of Ray’s birth, American film director Martin Scorsese proclaimed that his films “are truly treasures of cinema, and everyone with an interest in film needs to see them”.

Stills from the films Pather Panchali and The World of Apu

Ray’s many admirers include a number of luminaries from science, as well as the arts. Chief among them was science writer and novelist Arthur C Clarke, who described Ray’s debut film Pather Panchali (1955) – the first of his classic Apu Trilogy – as “one of the most heartbreakingly beautiful films ever made”. A founder of econophysics, Eugene Stanley, wrote of the “Bengali genius” Ray in a 1992 issue of the statistical mechanics journal Physica A (186 1) – remarking that the director’s recent death had “left the world immeasurably poorer”. And today, a leading Indian theoretical physicist, Dipankar Home, says that he is “amazed by the profundity and steadfastness of Ray’s commitment to a scientific outlook, permeating his varied creations”.

Prolific polymath

Focusing on Bengal but also depicting other parts of India, Ray’s films cover everything from village poverty to urban wealth; they stretch from the 19th-century British Raj to the present-day; and they include comedies, detective stories, musicals, romances and tragedies. Uniquely among great film directors (apart from Chaplin), Ray wrote the script, cast the actors, designed the costumes and sets, operated the camera, edited the film and composed its score, drawing on his passion for Indian and western music. But unlike Chaplin, Ray was not keen to act himself, despite interest from leading Hollywood producers, such as David Selznick. As Ray once explained to the admiring but slightly offended actor Marlon Brando, “No it’s better behind the camera… It would be too tedious, you see”!

In addition to film-making, Ray was a sought-after graphic designer and illustrator, and a bestselling writer of short stories and novels, aimed at both children and adults. His first job, from 1943 to 1956, was with a British advertising agency in Kolkata, and he continued writing fiction until his death. His books, which were later extensively translated from Bengali into English, include both detective stories and science fiction, partly inspired by his early reading of Arthur Conan Doyle, Jules Verne and H G Wells. The Bengali detective he created in his 1965 short story Feludar Goendagiri (English title Danger in Darjeeling) was influenced by his childhood love of Sherlock Holmes. Nicknamed Feluda, the character was also dramatized on screen by Ray as well as being the star of over 30 of his stories and novels. Indeed Feluda has become Ray’s most familiar creation in today’s India, especially with younger audiences.

Fascinated by science

Ray’s grandfather Upendrakisore and father Sukumar were notable writers and illustrators themselves, and both were trained in science (unlike Satyajit). Their stories, comic verse and drawings remain much loved in Bengal today, and their influence on Ray is clear from his many films that reveal the director’s lifelong fascination with science – covering everything from physics and astronomy to medicine and psychology. Perhaps the most famous scene in Pather Panchali shows the curiosity and awe induced in the uneducated village boy Apu by the sound of humming telegraph wires, immediately followed by the boy’s first sight of a passing steam train scattering black smoke across a field of white pampas grass. And in Ray’s last feature film, The Stranger (1991), an avuncular anthropologist enchants his schoolboy great-nephew in Kolkata with a puzzling question: why are the apparent sizes of the Sun and the Moon in the sky similar, and the Earth just the right size for total solar and lunar eclipses? When the boy has no answer, his great-uncle tells him: “I say it’s one of the greatest mysteries of the universe. The Sun and the Moon. The King of the Day, the Queen of the Night, and the shadow of Earth on the Moon … all exactly the same size. Magic!”

Satyajit Ray at work in his drawing room

In 1983, in an Indian magazine interview, Ray explained his fascination with science, saying that “this universe, and its incessant music, may not be entirely accidental. Maybe there is a cosmic design somewhere which we don’t know”. Talking about the wonders of nature, he continued, “Watch the protective colourations of birds and insects. The grasshopper acquires the exact shade of green that helps it merge in its surroundings. The marine life and the shore birds put on the exact camouflage. Could it all be coincidence? I wonder. I don’t mystify it either. I think someday the human mind will explore all the mysteries of life and creation the way the mysteries of the atom have been explored.”

Visitor from other worlds

This attitude triggered Ray’s highly original science-fiction film project The Alien, which was taken up by Hollywood in 1967. It emerged in 1964 from a letter written by Ray to Clarke at his home in Sri Lanka, requesting his good wishes for a Kolkata science-fiction cine-club. Clarke replied expressing admiration for Ray’s films and a correspondence developed, which led to their talking in London after watching Clarke’s collaborator Stanley Kubrick – who revered Ray – directing 2001: A Space Odyssey. Ray outlined his idea for the project, and Clarke found it compelling enough to discuss it with another friend Mike Wilson – a flamboyant film-maker and professional skin-diver. Wilson, who was a keen sci-fi fan, volunteered to sell the project internationally.

As already mentioned, The Alien stars a small humanoid creature whose spaceship splashes down in a Bengali village pond where most (but not all) villagers take it to be a submerged temple and begin to worship it. The exceptions include Haba, a poor boy who survives off stolen fruit and begging and who forms a rapport with the alien creature after it has entered his dreams at night and played with him. Another doubter is Mohan, a sceptical journalist from Kolkata, who questions the existence of godly beings. There is also Joe Devlin, a “can-do” US engineer, who distrusts anything he has not personally experienced.

Devlin is in this backwoods area to drill tube-wells on behalf of a dubious Indian industrialist called Bajoria. On seeing the spire, Bajoria instantly perceives its possibilities as “the holiest place in India”. He offers Devlin money to pump out the pond, so its floor can be covered with marble and a marble structure built with a little plaque saying: “Salvaged and restored by Gaganlal Laxmikant Bajoria”!

Title page of the script of "The Alien" and front cover of a collection of short stories by Ray

The extra-terrestrial creature has other ideas though. Consumed with playful curiosity about the world in which it has just landed, it invisibly gets up to all sorts of very visible mischief: ripening a villager’s corn overnight; making a mango tree belonging to the meanest man in the village fruit at the wrong time of year; causing an old man’s corpse lying on its funeral pyre to open its eyes in front of his grandson; and other inexplicable pranks.

Ray drafted The Alien’s screenplay in Kolkata during early 1967, watched by Wilson, who made some useful suggestions, including the golden colour of the spaceship. Ray then proposed that British comedian Peter Sellers should fill the role of Bajoria well. He had admired Sellers in Kubrick’s Dr Strangelove and knew that Sellers had already played an Indian in The Millionairess. Soon, Ray and Sellers met in Paris over lunch arranged by Wilson, and Sellers apparently accepted the role enthusiastically.

The next stop on Ray’s Alien tour was Los Angeles, after he received a sensational cable from Wilson that Columbia Pictures wanted to back the film. There Ray was taken aback to discover mimeographed copies of his screenplay bearing the legend “copyright 1967 Mike Wilson & S Ray” circulating in Hollywood. He also met Sellers again, then filming another Indian role in The Party, but sensed the actor had developed doubts. After being whisked off by Wilson to a series of glamorous parties with film stars, Ray left Hollywood for Kolkata convinced that his innovative Indian project was “doomed”.

To its credit, Columbia remained committed, subject to Wilson’s withdrawal. Ray felt that Clarke was the only person who might bring this about. Clarke responded with a letter saying that Wilson had shaved his head and gone off to meditate in the jungles of south India as a monk. A brief letter from Wilson to Ray finally followed, relinquishing any rights to the Alien screenplay.

Striking similarities

For more than a decade Ray was encouraged by Columbia to revive the project and continued to treat it as possible. Not until he saw Spielberg’s E.T. did he give up hope. E.T., which began life in 1981 as a Columbia project, had much in common with Ray’s concept of The Alien. First, there is the benign nature of the creature. Then, as Ray told me in the mid-1980s while I was researching his biography, there is the fact that it is “small and acceptable to children, and possessed of certain superhuman powers – not physical strength but other kinds of powers, particular types of vision, and that it takes an interest in earthly things”.

Ray felt, though, that the appearance of his alien was much more interesting. “Mine didn’t have any eyes,” he continued. “It had sockets so the human resemblance was already destroyed to some extent. And mine was almost weightless and the gait was different. Not a heavy-footed gait but more like a hopping gait. And it had a sense of humour, a sense of fun, a mischievous quality. I think mine was a whimsy.” Ray could understand the audience appeal of Spielberg’s alien, though he found E.T. “a bit corny at times”. But he did not care for the extent to which the alien had been humanized. “It ought to be more subtle than that,” he said. “But the children are marvellous. Spielberg has talent in handling children; I’m not sure about otherwise.”

The first outsider to spot the similarities was Clarke, who described them as “striking parallels”. Telephoning Kolkata from Sri Lanka in 1983, he suggested Ray write politely to Spielberg about the resemblances. “Don’t take it lying down,” advised Clarke, according to Ray. But despite the fact that Ray remained firmly of the view that E.T. “would not have been possible without my script of The Alien being available throughout America in mimeographed copies”, he did not want to pursue the matter further. Ray agreed with Clarke that “artists have better things to do with their time”; and he knew that Spielberg’s view, according to a letter Clarke wrote to the Times newspaper in 1984, was that he was too young to have been influenced by Ray’s screenplay.

“Tell Satyajit I was a kid in high school when his script was circulating in Hollywood,” Spielberg told his friend Clarke on a visit to Sri Lanka “rather indignantly” – which hardly resolves the doubts, especially as Spielberg in the late 1960s was already an adult getting started in movies. According to Clarke, Ray and Spielberg were “two of the greatest geniuses the movies have ever produced”. However, as Scorsese publicly remarked in 2010, “I have no qualms in admitting that Spielberg’s E.T. was influenced by Ray’s Alien. Even Sir Richard Attenborough pointed this out to me.”

Naturally, Ray regretted that his film never got made. His only consolation was that the screenplay’s delicate effects might well have been crushed by crass Hollywood production values, especially since the story was located in India. One can easily imagine the fate of Ray’s Bengali “whimsy” in Hollywood hands. Perhaps it was for the best that Ray’s project evanesced like the alien spaceship’s lift-off from the pond in the finale of the screenplay – before the Bajorias of Beverly Hills could pump out the water and get a commercial grip on it.

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