Dynamic PET images of 100 ms frames alternating between end-diastolic and end-systolic phases of five cardiac cycles. (Courtesy: PNAS 10.1073/pnas.1917379117)
The uEXPLORER is a 194-cm-long total-body PET/CT scanner developed by a research team at UC Davis and manufactured by United Imaging Healthcare of Shanghai. The UC Davis team has now shown that combining this ultrasensitive scanner with an advanced image reconstruction method enables capture of real-time videos of blood flow and heart function (PNAS 10.1073/pnas.1917379117).
The researchers developed a method to perform ultrahigh-temporal-resolution dynamic PET, based on the use of kernel expectation maximization reconstruction. Working with Zhongshan Hospital, they tested their proposed approach by injecting 256 MBq of the PET tracer 18F-FDG into a leg vein of a healthy 60-year-old female volunteer. Immediately after injection, they used the uEXPLORER to perform a 60 min total-body dynamic scan.
To demonstrate the high temporal resolution for capturing fast tracer dynamics and real-time cardiac motion, the researchers divided the first minute of recorded PET data into 100 ms frames and reconstructed more than 600 consecutive frames. The reconstructed images demonstrated the scanner’s ability to visualize cardiac motion with high clarity, capturing changes in the cardiac blood pool, with clear delineation of the end-systolic and end-diastolic phases.
The team also created a video of the injected tracer travelling through the body with 100 ms temporal resolution. The video shows the tracer moving up the body to the heart, flowing through the right ventricle to the lungs, back through the left ventricle and on to the rest of the body.
“The breakthrough in this work is to capture the ultrafast whole-body dynamic tracer imaging with EXPLORER at the same time,” says UC Davis’ Jinyi Qi. “We can see global changes with improved image quality at a timescale of 100 ms, which was never seen before using any medical imaging modalities.”
The team generated time–activity curves (TACs) in four regions-of-interest – within the left ventricle (LV), ascending aorta, descending aorta and myocardium – during the first minutes after tracer injection. The curves showed a staircase pattern as new blood entered the LV in the diastolic phase of the cardiac cycle (during which, radiotracer concentration in the LV changed) and was pumped into the aorta in the systolic phase (when concentration in the aorta changed).
The researchers also observed that the TAC of the descending aorta was lower than those of the LV and ascending aorta and that the myocardium TAC had a clear cyclical rhythm from the heartbeat. They point out that none of these observations would be possible at the lower temporal resolution previously used in dynamic PET imaging.
The uEXPLORER’s ability to create dynamic PET images on 100 ms timescales should allow study of cardiovascular function, fast pharmacodynamics, use of shorter-lived radionuclides, and characterization of normal and abnormal brain function by measuring cerebral blood flow and cerebral metabolic rate of oxygen.
The high temporal resolution can also be used to freeze motion, either physiological (such as cardiac and respiratory motion) or involuntary body motion, which improves the spatial resolution of reconstructed images. Finally, the researchers note that high temporal resolution combined with uEXPLORER’s total-body coverage could enable new studies examining the dynamic function and interaction of multiple organs – such as the brain and heart, or the brain and gut – simultaneously.
“Currently the uEXPLORER scanner is routinely used at UC Davis for both clinical scans and a variety of research studies,” Qi tells Physics World. “For the high temporal resolution total-body PET, we plan to use it to study cardiac functions and also brain-heart interactions in the near future.”
In the spotlight: Natalia Ruiz plays fictional physicist Agustina Ruiz Dupont in a new film that aims to tell the story of those scientists – often women – who have been forgotten or erased from history. (Courtesy: Instituto de Astrofísica de Andalucía, IAA-CSIC)
By any measure, Agustina Ruiz Dupont had an incredible career. This Spanish theorist was Marie Curie’s star student at the Sorbonne University in Paris. She impressed Einstein at the 1930 Solvay conference (which she attended, unbeknown to most science historians), and later joined the Las Sinsombrero movement of female intellectuals in Madrid.
Driven by a passion to share her knowledge, Dupont also travelled through Spain giving musical-inspired performances under the stage name La Fotoncita de Jerez (“little photon of Jerez”). Ultimately, things took a dark turn for her, when she disappeared shortly before the Spanish Civil War. Rumour has it, she had managed to personally offend General Franco through one of her shows.
There’s just one small catch – Agustina Ruiz Dupont never actually existed.
Dupont (played by Natalia Ruiz) is the fictional character at the heart of a recent Spanish-language docufiction film El Enigma Agustina, directed by astrophysicists Manuel González and Emilio J García. She might not be real, but we’re told that pretty much everything else in the film is true. Dupont represents all the real scientists and thinkers – especially women – from the period preceding the Spanish Civil War (1936–1939) who were forgotten or erased from history. Among them is Felisa Martín Bravo, who in 1926 became the first Spanish woman to get a physics doctorate, before she was stripped of her academic functions by the Franco regime.
The bulk of the film is set in the present day, as historian Esther Vidal (played by Nerea Cordero) embarks on a PhD about the Spanish theorist Blas Cabrera, who really did attend the 1930 Solvay conference. Early in her research, Vidal catches wind of a mysterious baúl (trunk) that turned up in one of Franco’s private rooms during restoration of Madrid’s El Pardo Palace in the 1980s, following the dictator’s death. Within the trunk were Dupont’s PhD thesis (supervised by Cabrera), personal letters from Curie and Einstein, a photo of Dupont at the Solvay Conference, along with a flamenco shawl and a few other cultural items from the time.
Determined to discover more about Dupont’s life, Vidal switches the focus of her PhD to pursue the case. She recruits the science communicator Andrés García (played by Antonio Leiva) who had written a piece about the Solvay conferences. (Later, Garcia openly admits to having copy-and-pasted most of the article from Wikipedia, but this chancer attitude proves useful to the investigation.) The pair are overcome by questions: Why has nobody heard of Dupont before? Why were these items in Franco’s personal room? What happened to Dupont during the Civil War?
The rest of the film tracks the investigation – via Paris, Granada and Madrid – as Dupont’s story becomes more intriguing at every turn. Along the way, we occasionally jump to a black-and-white scene, seemingly in the 1930s, of Dupont in the dressing room of an unspecified theatre, passionately conversing with her musician cousin about her intellectual life. She talks about her friendship with Curie, her desire for a unified theory of physics, and her deep conviction to communicate scientific ideas with the Spanish public.
While the film’s plot may often seem far-fetched, it is always entertaining – you may wish to skip the next few lines to avoid spoilers. For instance, we learn that Dupont had a fling with Erwin Schrödinger, a credible plot device, given that Schrödinger was apparently a notorious womanizer. Indeed, it’s of historical record that Schrödinger (then married) took a mystery girlfriend with him to the Alps shortly before Christmas 1925, the trip where he famously crystallized the Schrödinger equation, which he published in January 1926. Yep, you guessed it: in the film, Dupont is revealed to be the girlfriend.
In terms of its theme, El Enigma Agustina reminds me of José Luis Cuerda’s 1999 film La Lengua de las Mariposas (“The butterfly’s tongue”), which also represented the Spanish nationalists’ brutal clampdown on freedom of thought during and after the Civil War. González and García, the film’s directors, are both based at the Astrophysics Institute of Andalucia (IAA-CSIC) and along with their scientific qualifications have extensive experience in communicating science. The duo’s creative approach to storytelling is unusual, and keeps the audience engaged. Indeed, I was gripped by the story and left wanting to know what happens next. Speaking at the international premiere of the film in London on 19 October 2019, the directors said they were influenced by the Spanish writer Almudena Grandes. Specifically, they were inspired by one of her stories about how progress does not always happen in straight lines.
El Enigma Agustina is timely, as Spain’s uneasy relationship with its past has been dug up once more – quite literally, as Franco’s remains were exhumed from the Valley of the Fallen monument north of Madrid and reburied in a more modest location last October. While most mainstream politicians agreed it was a necessary act, it reopened old wounds and right-wing parties made major gains at the Spanish general election in November.
Much of the Spanish Civil War period is shrouded in contested histories and partially erased information
Without drifting into a full armchair analysis, it strikes me that current tensions are fuelled by the fact that so much of the Civil War period is shrouded in contested histories and partially erased information. For example, Spanish historians are only now starting to learn about the achievements of Las Sinsombrero, the group that Dupont joins in the film. These female artists and intellectuals took their name from the act of removing their hats while passing Madrid’s Puerta del Sol, a gesture to display their freethinking attitude. Unlike their male contemporaries– including the artist Salvador Dalí and the poet Federico García Lorca – their achievements are only starting to be recognized.
A small criticism of the film is that its political leaning is not the most subtle at times. It is fascinating to learn about the ideals of the Second Spanish Republic (1931–1939), which included giving grants to more than 400 women to study science, many of whom took up positions at overseas universities. But this era is presented as a golden age for Spain, and there is no mention of the high unemployment levels and poverty linked with the global economic depression. Including this would have provided important historical context for that era, especially for a non-Spanish audience.
Ultimately, though, the film is a triumph of blending science with politics and history. The greatest praise you can give to any documentary is that it keeps you gripped throughout and leaves you craving more answers. El Enigma Agustina achieves that with gusto.
A way of using light to convert a normal optical material into a frequency doubler has been developed by Mohammad Taghinejad and colleagues at the Georgia Institute of Technology. The technique could have a range of applications from creating all-optical information-processing devices to studying quantum-mechanical tunnelling.
Frequency doubling is an optical effect that occurs in spatially asymmetrical materials that have a second-order nonlinear susceptibility. Two photons with the same frequency can interact with the material and combine to form a single photon with twice the frequency of the original photons. While most crystalline materials do not have the appropriate asymmetry in the bulk, frequency doubling can occur at surfaces and interfaces. However, relying on these very thin regions is not ideal for creating practical devices.
Researchers have managed to create bulk materials with the appropriate asymmetries by applying mechanical strain or electrical signals to materials that are normally symmetric. Now, Taghinejad and colleagues have come up with a way of creating a temporary asymmetry in titanium dioxide by applying laser light.
Gold triangles
The team’s device comprises a 25 nm-thick film of amorphous titanium dioxide – normally a symmetric material – that is sandwiched between an opaque gold film and an array of thin gold triangles. When illuminated by picosecond pulses of red laser light, electrons in the triangles gain energy and some of these “hot electrons” move onto the titanium dioxide via the triangle tips. This momentarily breaks the material’s symmetry. Pulses from an infrared laser are also fired at the device and analysis of the reflected light reveals the presence of frequency-doubled blue photons.
While the asymmetry was induced almost instantaneously within the titanium dioxide film, the team found that the second-order effects endured for several picoseconds after the red pulse ended. They also showed that their setup was dynamically tuneable, with the number of migrating electrons depending on laser intensity. Furthermore, they found that the effect can be sustained using a continuous laser beam.
This is the first example of asymmetry being created using optical techniques alone and the discovery could lead to a wide range of scientific and technological applications. The ability to use one light signal to control frequency doubling in another would be very useful for creating all-optical components for computing and telecommunications. Other potential applications of the technique include monitoring the quantum-mechanical tunnelling of electrons.
In future studies, Taghinejad and colleagues plan to explore how the strength of second-order effects can be maximized through certain combinations of metals and semiconductors; using different material shapes; and using lasers with different frequencies.
An international team of scientists has developed an affordable microfluidic-based sensor able to track variations in levels of metabolites and nutrients in a patient’s blood simply by analysing their sweat. The device could be used to diagnose and monitor a wide spectrum of conditions, with an emphasis on gout (Nature Biotechnol. 10.1038/s41587-019-0321-x).
If you suffer from trypanophobia (the fear of needles), then fear not, as technological help is on the way. While blood sampling used to be the only accurate way to monitor key metabolites such as tyrosine and uric acid (UA), important indicators of metabolic disorders and gout respectively, it might soon be possible to obtain the same information from a wearable sensor. No need to have a needle stuck in your arm anymore.
The device is the result of a cooperation between American and Chinese researchers from Caltech, Peking University, Santa Clara University, Princeton University and UCLA. It contains microfluidic channels and graphene biosensors engraved onto plastic sheets by a low-cost carbon dioxide laser.
Lead author Yiran Yang (left) and senior author Wei Gao. (Courtesy: Wei Gao)
This design makes the sensor easy to manufacture and enables the monitoring of small concentrations of sweat compounds. In contrast, existing prototypes can only target compounds appearing in high concentration in sweat, such as electrolytes, glucose and lactate. The sensor can also record respiratory rate, heart rate and temperature and transfer all data via Bluetooth.
“Such wearable sweat sensors have the potential to rapidly, continuously and noninvasively capture changes in health at molecular levels,” lead author Wei Gao says. “They could enable personalized monitoring, early diagnosis and timely intervention”.
A battery of tests
To see how well the sensor performed, the researchers compared data collected in healthy individuals and patients. For example, since tyrosine is influenced by physical fitness, they compared their levels in five trained athletes and five physically untrained subjects, and observed that the sensors showed lower levels of tyrosine in the sweat of the athletes.
The team was particularly interested in using the device to monitor gout, which is characterized by high levels of UA in the body that begin to crystallise in joints, causing irritation and inflammation. By monitoring UA levels in six healthy individuals initially subjected to fasting conditions and later fed with a meal rich in purines – compounds that metabolise into UA – the researchers observed that UA levels peaked in all of them after eating.
They similarly found that four subjects with hyperuricemia and six untreated patients with gout had higher sweat UA levels two hours after a regular meal than five healthy subjects, confirming the sensor’s ability to pick up variations in UA. Its accuracy also proved excellent, as UA levels derived from sweat were very closely related to those found in the blood serum in 46 biologically independent samples.
Informing patients’ health
Although the sensor has only been used in small samples and needs to be tested prospectively to noninvasively monitor disease development, the study holds promise. With its high sensitivity, ease of manufacture and Bluetooth connectivity, the sensor offers the potential to mass-produce a reliable alternative to needles that will allow patients to have real-time information about their health. Ideally, this would even allow them to adjust their own medication levels and diet as required.
“Considering that abnormal circulating nutrients and metabolites are related to a number of health conditions, the information collected from such wearable sensors will be invaluable for both research and medical treatment,” Gao concludes.
Ballet dancers moving in harmony to the rhythm of music. Violinists in an orchestra playing perfectly in unison. A school of fish swimming gracefully together in the sea.
Synchronization – two or more events happening at the same time – is one of the most common phenomena in nature. Extending from unconscious entities to human beings, it’s even an Olympic sport in the form of synchronized swimming or diving. Synchronization is essential to life too. Pacemaker cells, for example, have to fire electrical discharges synchronously to ensure our hearts beat properly.
For physicists, synchronization is particularly intriguing in inert systems. Place two identical metronomes on a wooden bar mounted on two fizzy-drink cans, and you’ll find that the rhythms of these mechanical devices – used by musicians to keep time – can synchronize within minutes or even seconds. But how do the metronomes “decide” to reach a common rhythm? And, more importantly, why do they do this?
To answer those questions, we need to wind back to the 17th century and enter the world of Christiaan Huygens – perhaps the greatest Dutch scientist of all time. Besides having a passion for astronomy and optics, Huygens was also a supreme mathematician. Indeed, his 1673 book Horologium Oscillatorium is one of the most important scientific works of his era, with Isaac Newton believing Huygens to be “the most elegant writer of modern times”.
Huygens also made various inventions, including the pendulum clock, which he believed could help to solve one of the greatest scientific challenges of the day. Lacking the location technology we take for granted today, sailors had to determine their latitude by estimating the height of the Sun above the horizon and the angle its rays make with the Earth’s equator. However, they had no physical reference for determining their longitude – how far east or west their ship was at sea.
Most ideas for solving the “longitude problem” consisted of determining the difference between the local time (obtained from the Sun) and the “reference” time at the port from where the ship had set sail. But Huygens wanted to show that his pendulum clocks would be the answer by providing a reliable and accurate reference time to sailors. And so it was that in 1664 Huygens planned a daring experiment with Alexander Bruce, one of the dozen men who had founded the Royal Society in London just a few years before.
Struggling at sea: Christiaan Huygens invented the pendulum clock as a (failed) attempt to solve the longitude problem, whereby sailors needed a clock that worked accurately at sea to determine their exact position east or west. (Courtesy: iStock/hitforsa)
A problem of motion
To test their hypothesis, Huygens and Bruce placed two pendulum clocks on board a ship commanded by the British admiral Robert Holmes. The idea of having multiple clocks was that if rough seas stopped one of the clocks from working, at least the other would be running at the correct frequency.
According to the instructions Huygens provided, the ship’s sailors were meant to look at the time indicated by the clocks (set to the time of the place of departure) and then determine the local time (indicated by the Sun). If the time on the clocks was later than the local time, it meant the sailors were moving east. But if the clock time was earlier, they were heading west. In both cases, each hour of difference was equivalent to 15° of longitude.
Departing from the island of St Thomas off the coast of Guinea in west Africa, Holmes’ vessel initially set off in a westerly direction. But after a few days, the master of the ship realized they were running out of drinking water. Using the time indicated by the pendulum clocks, however, Holmes was able to figure out the vessel’s location – barely 30 nautical leagues from one of the Cape Verde islands in the mid-Atlantic. Thanks to this vital information, Holmes steered the vessel towards the island and arrived safely the next day, exactly as expected from the calculations carried out using data from the clocks (1665 Phil. Trans.1 13).
Based on this successful trial, Huygens – who was as much an entrepreneur as a scientist – drew up a business plan and started to prepare his maritime pendulum clocks for sale. Huygens also published his instructions to determine longitude at sea with these devices (1669 Phil. Trans. 4 937). There was, though, one snag with Huygens’ set-up. It’s almost impossible to build two identical pendulum clocks, which means that one will always be slower or faster than the other. So if one of the clocks were to stop due to rough seas, then even if the sailors reactivated it to match the time of the other clock, it could be substantially “out” and give a wrong longitude. Even an error of just four minutes would lead to a 1° error in the ship’s longitude, which could be disastrous.
Double take: Christiaan Huygens was not just one of the greatest Dutch scientists, but he also invented the pendulum clock and was the first person to observe how pairs of them can synchronize. (Courtesy: The Print Collector/Heritage Images/Science Photo Library)
Moving in sympathy
While working on the longitude problem, however, Huygens was surprised to discover that if he hung two of his pendulum clocks from a common support – a wooden bar supported by two chairs – the devices kept pace relative to each other. The two pendulums always swung at the same frequency albeit in opposite directions to each other. According to Huygens’ reports, it took the two pendulums about half an hour to reach this out-of-phase synchronization. In a letter to the Belgian mathematician René-François de Sluse, dated 22 February 1665, Huygens referred to this odd phenomenon as “the sympathy of two clocks”.
Huygens referred to this odd phenomenon as “the sympathy of two clocks”
For Huygens the beauty of the system was that even if one of the clocks stopped, the other would be keeping the correct time – and hence give the correct longitude measurement. In 1667 he therefore carried out a second maritime experiment, installing two linked clocks on a ship bound for the West Indies. Unfortunately, the clocks came to a stop in a storm and the sailor responsible for them failed to follow the instructions for resetting the devices – making it impossible to measure the time on board with them anymore.
Due to the practical difficulties, Huygens began to realize that pendulum clocks might not be the solution to the longitude problem, at least not in rough seas. Indeed, in December 1683, he sent a letter to the Dutch mathematician Bernard Fullenious, writing that “there is no small hope that it will succeed”. In the end, it was the English clockmaker John Harrison who came up with the final solution to the longitude problem almost a century later.
Further progress on what’s now known as “Huygens synchronization” did not occur until 1740 when John Ellicott – a renowned English clockmaker – submitted a manuscript to the Royal Society. In it he described an “odd” phenomenon: when two pendulum clocks were placed next to each other so that the pendulums were oscillating in the same plane, one of them always stopped working after about two hours, whereas the other kept swinging normally. Ellicott concluded that the two pendulum clocks were influencing each other through the common structure on which they were placed.
Little further progress was made on synchronized pendulums until 1873 when the British astronomer and meteorologist William Ellis, while working at the Royal Observatory in Greenwich in 1873, observed two pendulum clocks that had been placed on a wooden stand. Over nine consecutive days, he noticed that the times indicated by the clocks were identical, even though one pendulum was swinging to the left and the other to the right. The pendulums, in other words, were oscillating at the same frequency, but in opposite directions – exactly as in Huygens’ experiment.
Ellis recounted his findings in a paper published in the Monthly Notices of the Royal Astronomical Society (33 480), where he referred to the phenomenon of two out-of-phase pendulums as a “sympathy” despite neither he – nor Ellicott for that matter – mentioning Huygens’ earlier observations. In fact, the first formal attempt to explain the synchronized motion in Huygens’ pendulum clocks was only made in 1906 by the Dutch mathematician Diederik Korteweg and further progress on this mysterious phenomenon did not occur until the Soviet Union in the 1980s. Working at the Mekhanobr Institute in what was then Leningrad, Iliya Izrailevich Blekhman reproduced Huygens’ experiment using two small pendulum clocks placed on a common wall. Blekhman improved Korteweg’s mathematical model by adding terms describing the source of energy that keeps a pendulum clock running.
Remaining mysteries
All these studies have helped to shed light on the secret of self-synchronization in pendulum clocks. Although Christiaan Huygens didn’t have the mathematical tools to explain the strange phenomenon – differential calculus hadn’t been invented in the mid-17th century – we now know that he correctly understood the underlying mechanism. The synchronization is due to the clocks transferring energy to each other via the coupling bar in the form of mechanical vibrations. The clocks start moving exactly out of phase, in other words, when the vibrations exerted by one pendulum clock on the coupling bar are exactly cancelled by the vibrations exerted by the other.
But many questions remain unanswered, more than 350 years after Huygens’ discovery. What, for example, are the “minimal” requirements for self-synchronization? Will any pair of pendulum clocks eventually synchronize – or only certain types? And can you synchronize more than two pendulums? Only since the start of this millennium have scientists started shedding further light on these questions.
In 2002 a team led by Kurt Wiesenfeld at Georgia Tech in the US designed and built a simplified version of Huygens’ experiment using mechanical metronomes instead of pendulum clocks. They concluded that the sympathy observed by Huygens’ in his clocks is largely influenced by the coupling strength, which is the ratio of the total mass of the pendulums to the total mass of the coupling bar from which the clocks are hanging. A large ratio indicates a strong interaction between the pendulums, whereas a small ratio corresponds to a weak interaction. Furthermore, for a small ratio the pendulums synchronize with opposite phase, whereas for a large ratio the pendulums exhibit a “beating death phenomenon”, in which one pendulum keeps oscillating whereas the other comes to a stop (Proc. Roy. Soc. A458 563), as Ellicott had observed.
At about the same time, James Pantaleon from the University of Alaska Anchorage carried out a fascinating experiment consisting of two metronomes placed on a light wooden board sitting on two empty fizzy-drink cans so the whole system could roll. He found that the metronomes reached a common rhythm but oscillated in the same direction – rather than in opposite ways as Huygens and Ellis had seen.
Mystified by this finding, in 2005 we decided to create our own version of Huygens’ experiment at Eindhoven University of Technology. Our set-up consisted of two metronomes mounted on a rigid metal bar suspended from leaf springs (figure 1). Confirming previous findings, we observed at least two types of synchronized motion. If the bar is relatively light, the metronomes start to oscillate synchronously in the same direction. But if the metal bar is heavier than a certain value, they oscillate at the same frequency but in opposite directions, just as Huygens saw. The critical transition mass in our experiment was found to be 2.35 kg.
1 From old to new
(Courtesy: P G M Hamels)
This simplified version of Christiaan Huygens’ original 17th-century experiment on synchronized pendulums was created by the authors at Eindhoven University of Technology in the Netherlands. It consists of two mechanical metronomes coupled through a metallic bar, which is elastically attached to a fixed support by means of springs.
It appears that a light coupling bar facilitates the onset of complete synchronization because the coupling strength is then relatively large. A heavier bar, in contrast, has a weak coupling strength, which results in the metronomes oscillating out of phase. We also derived a mathematical model for our coupled metronomes based on Newton’s second law, which revealed that the key parameters governing the onset of self-synchronization are the metronomes’ mass and oscillation frequency, as well as the mass of the bar and the rigidity of the springs from which the bar is suspended.
Recently, we have reproduced a modern version of Huygens’ experiment (figure 2) using two “monumental” pendulum clocks that were designed and built by Relojes Centenario – a specialist clock-making firm in Zacatlán, Mexico. The pendulum in each clock consists of a 5 kg metal mass attached to the lower end of a wooden rod just under 1 m long. At the heart of each clock is a structure, known as an “anchor-escapement mechanism”, that maintains the motion of the pendulum and is responsible for the characteristic “tick-tock” sounds of pendulum clocks. Connected to weights suspended from the clock, this structure gives the pendulum a “kick” each time its angular displacement reaches a certain threshold, thereby regulating the motion of the pendulum as it swings.
2 Monument to history
(Courtesy: Luis Alberto Olvera Cardenas)
This elaborate modern version of Huygens’ experiment was built by the specialist clock-making company Relojes Centenario in Zacatlán, Puebla, Mexico, and appears in the firm’s museum. Consisting of two pendulum clocks coupled through a wooden structure, the clocks end up moving in complete synchronization. The pendulum in each clock consists of a 5 kg metal mass attached to a wooden rod roughly 1 m long.
Using this equipment, we noticed that, after about 30 minutes, the pendulums were both oscillating in the same direction and at the same frequency. The clocks stayed synchronized for as long as potential energy was stored in the weights to drive the escapement mechanism. Indeed, each clock has a device that rewinds the weights roughly every 30 minutes, which means they could keep running for as long as desired. If it wasn’t in place, the clock would have stopped after about 14 hours.
Using this equipment, we confirmed the secret behind the onset of synchronization – first observed by Huygens all those years ago. As he suspected, it is due to the transmission of vibrations – and thus energy – through the wooden structure on which the clocks are attached. The wooden table, in other words, is the channel by which the pendulums can communicate with each other and eventually “decide” on a common rhythm. Although our modern clocks sat on a pine table, whereas Huygens’ devices hung from a bar, both depend on the elastic deformation of a piece of wood.
The final word
But we have also made some new observations that Huygens never noted. For example, clocks that are placed on the same wooden table and start moving in synchrony are no longer reliable time-keepers, losing 47 seconds per hour, which is almost 19 minutes a day. So even if Huygens had persisted in his use of pendulum clocks to find longitude at sea, and even if those devices weren’t disturbed by stormy seas, they still wouldn’t have worked as good timekeepers (Sci. Rep. 6 23580).
Coupled pendulums can do other strange things too, including “quenching” (both clocks stop working), undergoing seemingly chaotic motion (the clocks oscillate irregularly), moving in an unsynchronized way and more.
So do we now completely understand Huygens’ synchronization? In short, no. Most mathematical models, including our own, aren’t complete in that they don’t consider all the deformations experienced by the wooden support on which the clocks are hanging.
We hope, however, that a complete model will one day be created, not least because Huygens’ system of coupled clocks could shed light on many other systems. Consider for instance two driven “unbalanced” rotors mounted on an elastic support. Under certain conditions, the rotors can revolve synchronously in the same direction but in other cases the rotors start spinning in opposite directions. The latter can be useful as it can cut or even eliminate the vibrations of the common support when the rotors are running. However, synchronized rotation in the same direction is not good as it can make the support vibrate massively, which is bad news if you’ve ever seen or heard a washing machine go out of control.
Studies of Huygens’ clocks could also shed light on the many similar synchronization effects in living organisms. The human body, for example, has many different kinds of oscillating rhythms – including respiration, heartbeat, neuronal activity and blood perfusion – and when these synchronize with each other, very little energy is used. That’s good, but synchronization can also be damaging or dangerous. The generation of epileptic seizures, for example, is closely linked to the (abnormal) synchronization of millions of neurons (see September 2019).
We therefore believe that a thorough investigation of the synchronized pendulum clocks that Huygens first studied all those years ago could help us to get a better understanding of synchronization phenomena throughout the physical and the biological world. Indeed, in one recent paper, we have designed and built a system of synchronized electronic neurons that can – thanks to an “adaptive” training procedure – control a mobile robot driving around an unknown environment while avoiding obstacles (International Journal of Bifurcation and Chaos26 1650196). Who’d have thought that Huygens’ early observations on his sympathetic clocks would ever lead to such uses?
Accelerated partial breast irradiation (APBI) is non-inferior to conventional whole-breast irradiation in preventing breast tumour recurrence, according to long-term findings of a trial of over 2100 women. The study demonstrated comparable survival following either treatment. However, moderate late toxicity and adverse cosmetic results were greater for women who received the twice-daily APBI (Lancet 10.1016/S0140-6736(19)32515-2).
For women with early-stage breast cancer, whole-breast irradiation after breast conserving surgery reduces local recurrence, improves survival and provides good cosmetic results. However, the treatment usually takes three to five weeks. APBI provides a more convenient radiation treatment, as it is delivered over one week or less. By targeting radiation dose to only the area surrounding the tumour and not the entire breast, APBI techniques enable larger radiotherapy fractions to be delivered in a shorter period with similar toxicity to whole-breast irradiation.
The goal of the RAPID trial was to determine whether external-beam APBI was non-inferior to whole-breast irradiation with respect to preventing local recurrence. Led by Timothy Whelan, of McMaster University and the Juravinski Cancer Centre, the study was performed at 33 cancer centres in Canada, Australia and New Zealand.
The trial included 2135 patients aged between 54 and 68 years with ductal carcinoma in situ or node-negative invasive breast cancer. Patients were randomized to receive either APBI (1070 women) or whole-breast irradiation (1065) following surgery. Tumour size was smaller than 1.5 cm for around 70% of participants.
While APBI can also be delivered via brachytherapy or intraoperative therapy, the researchers chose external-beam radiotherapy for the APBI arm because it is non-invasive, uses modern CT planning systems and because linacs are widely available. Women in the APBI group received 38.5 Gy in 10 fractions administered twice daily, separated by 6–8 hr over five to eight days. Patients in the whole-breast irradiation group received 42.5 Gy in 16 daily fractions, or 50 Gy in 25 fractions if large-breasted. Moderate- to high-risk patients in this group also received boost radiation to the primary tumour site.
Sixty-five patients developed breast cancer recurrence, including 37 who received APBI and 28 who underwent whole-breast irradiation. The eight-year cumulative rates of ipsilateral breast tumour recurrence (IBTR) were 3.0% in the APBI group and 2.8% in the whole-breast irradiation group. In more than half of these, recurrences occurred at or near the primary site, though the researchers note that more women had recurrence in other areas of the breast in the APBI group than in the whole-breast irradiation group.
The trial found no differences in disease-free, event-free survival and overall survival between the two groups, and comparable levels of death caused by breast cancer.
Acute radiation toxicity (grade 2 or greater) occurring within 90 days of the start of treatment was much higher for the whole-breast irradiation group. However, the reverse was true for late toxicities, with 32% and 4.5% of the APBI group experiencing grade 2 and 3 toxicities, respectively, compared with 13% and 1.0% for the whole-breast irradiation group.
APBI patients experienced worse cosmetic outcomes three, five and seven years after treatment (evaluated by the patients, nurses and physicians) than those who received whole-breast irradiation. The researchers attributed this to an increase in late subcutaneous tissue fibrosis and skin telangiectasia, toxic effects that led to a deterioration breast appearance that worsened over time.
As a result of these findings, the authors do not recommend the twice-daily APBI protocol, referencing more recent clinical APBI trials that suggest a 6-hr interval between external-beam radiation treatments is insufficient to repair radiation injury to healthy tissues. They note that APBI given once per day might not be associated with increased toxicity and is under ongoing investigation.
The RAPID trial also revealed the unexpected finding that more recurrences occurred away from the primary treatment site after APBI. “The inference is that the part of the breast not radiated is at a higher risk of developing either recurrence or a new cancer,” the authors wrote. They recommend additional research, because partial breast irradiation is based on the observation that most recurrences occur at or near the site of the primary tumour, an assumption that the RAPID trial findings now challenge.
A similar randomized trial of 4216 women treated at 154 centres in the USA, Canada, Ireland and Israel concluded that APBI was not equivalent to whole-breast irradiation for in-breast tumour control. However, the absolute difference in the 10-year cumulative incidence of IBTR was less than 1%. More patients in the APBI group had recurrence-free interval events, but the absolute difference between 10-year recurrence-free estimates was also small. Distant distance-free interval, disease-free survival and overall survival did not differ between patient groups receiving APBI and whole-breast irradiation (Lancet 10.1016/S0140-6736(19)32514-0).
Led by Frank Vincini of NRG Oncology and the Radiation Oncology Institute of St. Joseph Mercy Hospital, this clinical trial had broader eligibility requirements, allowing younger participants, with larger tumours, and including lobular cancer. A total of 4% of the APBI-treated group and 3% of the whole-breast irradiation group developed recurrent breast cancer. The team did not see a similar pattern of late toxicities to the RAPID trial.
“The findings support whole-breast irradiation. However, the absolute differences in ipsilateral breast-tumour recurrence were small, such that APBI might be an acceptable treatment in some patients,” the researchers concluded.
A textile coated with metal-organic frameworks (MOFs) could make an efficient anti-nerve agent material, according to experiments by researchers at Northwestern University in the US. The MOFs, which are based on zirconium, could act as catalysts to degrade chemical warfare agents such as VX and soman (GD) much faster than existing technologies, which are based on activated carbon and metal-oxide blends. The composite material, which might be used in protective suits and face masks for soldiers on the battlefield, does not require liquid water to work either, as previously thought.
MOFs are periodic nanoporous crystalline frameworks made from metal ions or clusters coordinated to organic ligands. The high surface area that comes from their porous structure means that they can be used in a host of applications, from sensing to gas separation and storage and catalysis.
Recent research has also revealed that the nanopores can effectively capture chemical warfare agents (CWAs) and then degrade them in a catalytic hydrolysis reaction. A team led by Omar Farha has now found that MOFs can continue to degrade these lethal chemicals, even when they are coated onto textile fibres.
MOFs can absorb enough water from the ambient humidity
Although the chemical degradation reaction requires water, the researchers say the nanopores in the MOFs can supply the needed water by absorbing it from ambient humidity. This will make it easier to deploy filters and other anti-nerve agent equipment based on this material in the field, Farha explains.
In their experiments, the team studied a Zr-based MOF with the chemical formula [Zr6O4(μ3-OH)4(OH)6(H2O)6(BTC)2]·nH2O (more commonly known as MOF-808). They began by applying a solution containing this material and polyethylenimine (PEI) to strips of cotton fabric. After allowing the fabric to dry overnight, they exposed it to DMNP, a nerve agent simulant commonly used in academic research labs. These tests showed that the MOF/PEI composite degraded DMNP even in the absence of water.
Fabric is durable and remains active
Farha and colleagues also tested the material’s durability. They found that the MOF remains securely adhered to the cotton and retains its crystallinity even when immersed in water and agitated for 24 hours. The composite’s catalytic activity also remains high after being exposed to ambient air for 100 days. In a final series of tests, they found the material retains its catalytic activity when exposed to sweat, atmospheric carbon dioxide and pollutants such as octane – environmental and physiological conditions similar to what a soldier might face on the battlefield.
The researchers, who report their work in the Journal of the American Chemical Society (JACS), hope their material will one day replace existing anti-CWA technology – namely activated carbon and metal-oxide blends, which react more slowly to nerve agents. Ultimately, they would like to create an improved MOF composite that instantly detoxifies these agents. “We are also interested in designing fabrics that can degrade multiple agents at the same time,” Farha tells Physics World.
Like most humans, I’m not a big fan of rats. I do, however, have a grudging admiration for their cunning and endless adaptability, and it turns out that some of their keen rat-sense may be down to mathematics. In a study of 523 whiskers from 15 individual rats, researchers in London and Manchester, UK found that the variety of whiskers on a rat’s cheek can be described by a simple mathematical equation.
The whiskers all have different lengths and shapes, and their distribution is such that each whisker is represented as an interval on the Euler spiral. The researchers conjecture that this distribution is “a manifestation of linear laws underpinning rat vibrissae [whisker] growth”, similar to the logarithmic spirals that appear in seashells. Also like seashells, the pattern of a rat’s whiskers has function as well as form. “The size and natural shape of each whisker, including its taper and intrinsic curvature, strongly influence the manner in which it deforms, and therefore, the tactile signals in the follicle,” they conclude.
We at Physics World always like to see physics techniques applied to solve problems in other disciplines. This week brought news (via Physics World contributing editor Belle Dumé) that researchers in France have used X-ray fluorescence spectrometry to analyse the colours painted on a statue of the Inca god and oracle Pachacamac. This measurement, combined with the first carbon-14 dating of the statue, has shed light on how the Inca civilization and its predecessors used and valued coloured pigments.
Among other findings, the researchers learned that the statue’s red pigment is not derived from blood, as was previously thought, but from a mercury-bearing ore called cinnabar. This is interesting because cinnabar is uncommon in the Andes, and the nearest source to the Pachacamac site is a few hundred kilometres away. Meanwhile, carbon-dating revealed that the statue was fashioned around 731 AD, nearly 800 years before the Spanish conquest of the Inca Empire, and 700 years before the empire reached its apogee. This confirms that the Pachacamac site was already important for local people before the Incas adopted it as a centre of pilgrimage.
Finally, I was intrigued by an article in the Guardian newspaper about the so-called “quantum bottleneck”. It seems that the world at large, and the UK in particular, is not producing enough people with the skills required for the nascent quantum-computing industry. The article quotes Doug Finke, who manages a website called Quantum Computing Report, as saying that the expansion of commercial quantum computing “has encouraged a number of academics to leave academia and join a company”. Finke goes on to warn that this academic exodus may create a shortage of professors to teach the next generation of students.
I don’t doubt that this is a real problem, but even so, whenever anyone bemoans the fact that physicists are leaving academia for industry, what I hear is, “Talented people are getting hired into well-paid permanent jobs, rather than spending the next five or more years of their lives in itinerant, ill-paid and insecure postdocs.” In a week that also saw a damning report from the Wellcome Trust on academic research culture, I can’t help but wonder whether some of these departing physicists are being pushed away by poor working conditions in universities, as much as attracted by high salaries in companies.
A new technique to make ultra-flat, wrinkle-free films of graphene could pave the way for a host of applications, including graphene-based flexible electronics and high-frequency transistors. The technique works by introducing protons into the film as graphene is synthesized using chemical vapour deposition (CVD), and its inventors say that it might be extended to other two-dimensional materials such hexagonal boron nitride (h-BN) and the transition-metal dichalcogenides (TMDCs). It could also aid the development of hydrogen storage devices made from layered 2D structures.
Graphene – a 2D honeycomb of carbon atoms just one atom thick – boasts several unique electronic properties. In contrast to conventional semiconductors, which have an energy gap between the electron valence and conduction bands, graphene is a “zero-gap” semiconductor. This means its electron valence and conduction bands just touch each other. At the point of contact, the electrons move at near-ballistic speeds, and their behaviour is governed by the Dirac equation for relativistic electrons – hence the name “Dirac point” for this section of graphene’s band structure.
Linear defects
So far, this electronic behaviour has only been observed in small flakes of graphene that have been shaved off, or exfoliated, from samples of bulk graphite. These flakes are not big enough to be practical for electronic circuits, and although larger, wafer-sized graphene films can easily be produced via CVD, their electronic performance is not as good. This is because CVD-grown graphene, unlike the exfoliated type, contains grain boundaries, atomic vacancies, impurities and wrinkles. These defects act as centres off which electrons can scatter as they travel, thus degrading the material’s electronic properties.
CVD-produced graphene is prone to wrinkling because the graphene must adhere to the surface of a substrate as it grows. If the thermal expansion coefficient of the substrate does not match that of the graphene itself, a change in temperature can lead to linear defects – wrinkles – forming as the ensemble strives to release compressive strain.
Researchers have attempted to reduce wrinkling by performing CVD at low temperatures, using substrates with a similar thermal coefficient to that of graphene, and developing single-crystalline substrates. A team of researchers led by Libo Gao at China’s Nanjing University has now shown that reducing the interaction between graphene and its substrate might be a good, alternative, strategy.
Intercalating hydrogen molecules
The Nanjing team began by introducing a plasma of protons – hydrogen ions – into the graphene’s growth chamber. During the CVD process, some of this hydrogen became intercalated between the graphene and its substrate, causing the two materials to decouple.
Gao and colleagues found that some of the wrinkles disappeared entirely from the graphene thanks to this proton penetration. They believe this is due to decreased van der Waals interactions between the carbon sheet and the substrate, as well as – possibly – an increase in the substrate’s distance from the growth surface thanks to the intercalation process.
The researchers also found that the electronic band structure of their graphene films shows a V-shaped “Dirac cone” (representing the density of states around the Dirac point) similar to the one observed in exfoliated graphene. They argue that this proves the proton-assisted CVD-grown graphene is indeed decoupled from its substrate.
The technique, which is detailed in Nature, could be extended to grow ultra-flat versions of other 2D materials, such as h-BN and the TMDCs, Gao says. It might also make it possible to develop hydrogen storage devices made from these layered materials.
“The physical and electronic properties of our ultra-flat graphene films are homogenous on the large scale, which means they might now be used in higher-performance electronic and photoelectronic devices,” he tells Physics World.
This episode of the Physics WorldWeekly podcast features an interview with Alan Bigelow, science director of Solar Cookers International, a non-profit organization that researches and promotes solar cooking. Bigelow explains how solar cookers work, why they are needed and the challenges of using such cookers in harsh environments. Caitlyn Hughes, the company’s executive director, also describes how the cookers can prove invaluable in refugee camps by removing the need for open-fire cooking.
We also hear from Dave Hughes, founding director of Novosound, which is developing novel thin-film ultrasound technology. The start-up company currently makes ultrasound systems for non-destructive testing, for customers in the aerospace or oil and gas inspection industries. Looking ahead, Novosound plans to move into the medical market, with products such as high-resolution ultrasound imaging systems. And a recent £3.3 million investment should certainly help them on their way.
And finally, we discuss why some new companies simply don’t manage to achieve such success and take a look at a couple of particularly bad business models.
