Category Archives: science

Mathematics, music, art, architecture, culture: Bridges 2015

Thanks to Alex Bellos and Tash Reith-Banks for their July 30, 2015 posting on the Guardian science blog network for pointing towards the Bridges 2015 conference,

The Bridges Conference is an annual event that explores the connections between art and mathematics. Here is a selection of the work being exhibited this year, from a Pi pie which vibrates the number pi onto your hand to delicate paper structures demonstrating number sequences. This year’s conference runs until Sunday in Baltimore (Maryland, US).

To whet your appetite, here’s the Pi pie (from the Bellos/Reith-Banks posting),

Pi Pie by Evan Daniel Smith Arduino, vibration motors, tinted silicone, pie tin “This pie buzzes the number pi onto your hand. I typed pi from memory into a computer while using a program I wrote to record it and send it to motors in the pie. The placement of the vibrations on the five fingers uses the structure of the Japanese soroban abacus, and bears a resemblance to Asian hand mnemonics.” Photograph: The Bridges Organisation

Pi Pie by Evan Daniel Smith
Arduino, vibration motors, tinted silicone, pie tin
“This pie buzzes the number pi onto your hand. I typed pi from memory into a computer while using a program I wrote to record it and send it to motors in the pie. The placement of the vibrations on the five fingers uses the structure of the Japanese soroban abacus, and bears a resemblance to Asian hand mnemonics.”
Photograph: The Bridges Organisation

You can find our more about Bridges 2015 here and should you be in the vicinity of Baltimore, Maryland, as a member of the public, you are invited to view the artworks on July 31, 2015,

July 29 – August 1, 2015 (Wednesday – Saturday)
Excursion Day: Sunday, August 2
A Collaborative Effort by
The University of Baltimore and Bridges Organization

A Five-Day Conference and Excursion
Wednesday, July 29 – Saturday, August 1
(Excursion Day on Sunday, August 2)

The Bridges Baltimore Family Day on Friday afternoon July 31 will be open to the Public to visit the BB Art Exhibition and participate in a series of events such as BB Movie Festival, and a series of workshops.

I believe the conference is being held at the University of Baltimore. Presumably, that’s where you’ll find the art show, etc.

Quantum and classical physics may be closer than we thought

It seems that a key theory about the boundary between the quantum world and our own macro world has been disproved and I think the July 21, 2015 news item on Nanotechnology Now says it better,

Quantum theory is one of the great achievements of 20th century science, yet physicists have struggled to find a clear boundary between our everyday world and what Albert Einstein called the “spooky” features of the quantum world, including cats that could be both alive and dead, and photons that can communicate with each other across space instantaneously.

For the past 60 years, the best guide to that boundary has been a theorem called Bell’s Inequality, but now a new paper shows that Bell’s Inequality is not the guidepost it was believed to be, which means that as the world of quantum computing brings quantum strangeness closer to our daily lives, we understand the frontiers of that world less well than scientists have thought.

In the new paper, published in the July 20 [2015] edition of Optica, University of Rochester [New York state, US] researchers show that a classical beam of light that would be expected to obey Bell’s Inequality can fail this test in the lab, if the beam is properly prepared to have a particular feature: entanglement.

A July 21, 2015 University of Rochester news release, which originated the news item, reveals more about the boundary and the research,

Not only does Bell’s test not serve to define the boundary, the new findings don’t push the boundary deeper into the quantum realm but do just the opposite. They show that some features of the real world must share a key ingredient of the quantum domain. This key ingredient is called entanglement, exactly the feature of quantum physics that Einstein labeled as spooky. According to Joseph Eberly, professor of physics and one of the paper’s authors, it now appears that Bell’s test only distinguishes those systems that are entangled from those that are not. It does not distinguish whether they are “classical” or quantum. In the forthcoming paper the Rochester researchers explain how entanglement can be found in something as ordinary as a beam of light.

Eberly explained that “it takes two to tangle.” For example, think about two hands clapping regularly. What you can be sure of is that when the right hand is moving to the right, the left hand is moving to the left, and vice versa. But if you were asked to guess without listening or looking whether at some moment the right hand was moving to the right, or maybe to the left, you wouldn’t know. But you would still know that whatever the right hand was doing at that time, the left hand would be doing the opposite. The ability to know for sure about a common property without knowing anything for sure about an individual property is the essence of perfect entanglement.

Eberly added that many think of entanglement as a quantum feature because “Schrodinger coined the term ‘entanglement’ to refer to his famous cat scenario.” But their experiment shows that some features of the “real” world must share a key ingredient of Schrodinger’s Cat domain: entanglement.

The existence of classical entanglement was pointed out in 1980, but Eberly explained that it didn’t seem a very interesting concept, so it wasn’t fully explored. As opposed to quantum entanglement, classical entanglement happens within one system. The effect is all local: there is no action at a distance, none of the “spookiness.”

With this result, Eberly and his colleagues have shown experimentally “that the border is not where it’s usually thought to be, and moreover that Bell’s Inequalities should no longer be used to define the boundary.”

Here’s a link to and a citation for the paper,

Shifting the quantum-classical boundary: theory and experiment for statistically classical optical fields by Xiao-Feng Qian, Bethany Little, John C. Howell, and J. H. Eberly. Optica Vol. 2, Issue 7, pp. 611-615 (2015) •doi: 10.1364/OPTICA.2.000611

This paper is open access.

Seeing quantum objects with the naked eye

This research is a collaborative effort between the Polytechnique de Montréal (or École polytechnique de Montréal; Canada) and the Imperial College of London (UK) according to a July 14, 2015 news item on Nanotechnology Now,

For the first time, the wavelike behaviour of a room-temperature polariton condensate has been demonstrated in the laboratory on a macroscopic length scale. This significant development in the understanding and manipulation of quantum objects is the outcome of a collaboration between Professor Stéphane Kéna-Cohen of Polytechnique Montréal, Professor Stefan Maier and research associate Konstantinos Daskalakis of Imperial College London. …

A July 14, 2015 Polytechnique de Montréal news release supplies an explanation of this ‘sciencish’ accomplishment,

Quantum objects visible to the naked eye

Quantum mechanics tells us that objects exhibit not only particle-like behaviour, but also wavelike behaviour with a wavelength inversely proportional to the object’s velocity. Normally, this behaviour can only be observed at atomic length scales. There is one important exception, however: with bosons, particles of a particular type that can be combined in large numbers in the same quantum state, it is possible to form macroscopic-scale quantum objects, called Bose-Einstein condensates.

These are at the root of some of quantum physics’ most fascinating phenomena, such as superfluidity and superconductivity. Their scientific importance is so great that their creation, nearly 70 years after their existence was theorized, earned researchers Eric Cornell, Wolfgang Ketterle and Carl Wieman the Nobel Prize in Physics in 2001.

A trap for half-light, half-matter quasi-particles

Placing particles in the same state to obtain a condensate normally requires the temperature to be lowered to a level near absolute zero: conditions achievable only with complex laboratory techniques and expensive cryogenic equipment.

“Unlike work carried out to date, which has mainly used ultracold atomic gases, our research allows comprehensive studies of condensation to be performed in condensed matter systems under ambient conditions” explains Mr. Daskalakis. He notes that this is a key step toward carrying out physics projects that currently remain purely theoretical.

To produce the room-temperature condensate, the team of researchers from Polytechnique and Imperial College first created a device that makes it possible for polaritons – hybrid quasi-particles that are part light and part matter – to exist. The device is composed of a film of organic molecules 100 nanometres thick, confined between two nearly perfect mirrors. The condensate is created by first exciting a sufficient number of polaritons using a laser and then observed via the blue light it emits. Its dimensions can be comparable to that of a human hair, a gigantic size on the quantum scale.

“To date, the majority of polariton experiments continue to use ultra-pure crystalline semiconductors,” says Professor Kéna-Cohen. “Our work demonstrates that it is possible to obtain comparable quantum behaviour using ‘impure’ and disordered materials such as organic molecules. This has the advantage of allowing for much simpler and lower-cost fabrication.”

The size of the condensate is a limiting factor

In addition to directly observing the organic polariton condensate’s wavelike behaviour, the experiment showed researchers that ultimately the condensate size could not exceed approximately 100 micrometres. Beyond this limit, the condensate begins to destroy itself, fragmenting and creating vortices.

Toward future polariton lasers and optical transistors

In a condensate, the polaritons all behave the same way, like photons in a laser. The study of room-temperature condensates paves the way for future technological breakthroughs such as polariton micro-lasers using low-cost organic materials, which are more efficient and require less activation power than  conventional lasers. Powerful transistors entirely powered by light are another possible application.

The research team foresees that the next major challenge in developing such applications will be to obtain a lower particle-condensation threshold so that the external laser used for pumping could be replaced by more practical electrical pumping.

Fertile ground for studying fundamental questions

According to Professor Maier, this research is also creating a platform to facilitate the study of fundamental questions in quantum mechanics. “It is linked to many modern and fascinating aspects of many-body physics, such as Bose-Einstein condensation and superfluidity, topics that also intrigue the general public,” he notes.

Professor Kéna-Cohen concludes: “One fascinating aspect, for example, is the extraordinary transition between the state of non-condensed particles and the formation of a condensate. On a small scale, the physics of this transition resemble an important step in the formation of the Universe after the Big Bang.”

Here’s a link to and a citation for the paper,

Spatial Coherence and Stability in a Disordered Organic Polariton Condensate by K. S. Daskalakis, S. A. Maier, and S. Kéna-Cohen Phys. Rev. Lett. 115 (3), 035301 DOI: 10.1103/PhysRevLett.115.035301 Published 13 July 2015

This article is behind a paywall but there is an earlier open access version  here: http://arxiv.org/pdf/1503.01373v2.

Molecules (arynes) seen for first time in 113 years

Arynes were first theorized in 1902 and they’ve been used as building blocks to synthesize a variety of compounds but they’re existence hasn’t been confirmed until now.

AFM image of an aryne molecule imaged with a CO tip. Courtesy: IBM

AFM image of an aryne molecule imaged with a CO tip. Courtesy: IBM

A July 13, 2015 news item in Nanowerk makes the announcement (Note: A link has been removed),

chemistry teachers and students can breath a sigh of relief. After teaching and learning about a particular family of molecules for decades, scientists have finally proven that they do in fact exist.

In a new paper published online today in Nature Chemistry (“On-surface generation and imaging of arynes by atomic force microscopy”), scientists from IBM Research and CIQUS at the University of Santiago de Compostela, Spain, have confirmed the existence and characterized the structure of arynes, a family of highly-reactive short-lived molecules which was first suggested 113 years ago. The technique has broad applications for on-surface chemistry and electronics, including the preparation of graphene nanoribbons and novel single-molecule devices.

A July 13, 2015 IBM news release by Chris Sciacca, which originated the news item, describes arynes and the imaging process used to capture them for the first time (Note: Links have been removed),

“Arynes are discussed in almost every undergraduate course on organic chemistry around the world. Therefore, it’s kind of a relief to find the final confirmation that these molecules truly exist,” said Prof. Diego Peña, a chemist at the University of Santiago de Compostela.

“I look forward to seeing new chemical challenges solved by the combination of organic synthesis and atomic force microscopy.”

There are trillions of molecules in the universe and some of them are stable enough to be isolated and characterized, but many others are so short-lived that they can only be proposed indirectly, via chemical reactions or spectroscopic methods.

One such species are arynes, which were first suggested in 1902, and since then have been used as intermediates or building blocks in the synthesis of a variety of compounds for applications including medicine, organic electronics and molecular materials. The challenge with these particular molecules is that they only exist for several milliseconds making them extremely challenging to image, until now.

The imaging was accomplished by means of atomic force microscopy (AFM), a scanning technique that can accomplish nanometer-level resolution. After the preparation of the key aryne precursor by CIQUS, IBM scientists used the sharp tip of a scanning tunneling microscope (STM) to generate individual aryne molecules from precursor molecules by atomic manipulation. The experiments were performed on films of sodium chloride, at temperatures near absolute zero, to stabilize the aryne.

Once the molecules were isolated, the team used AFM to measure the tiny forces between the STM tip, which is terminated with a single carbon monoxide molecule, and the sample to image the aryne’s molecular structure. The resulting image was so clear that the scientists could study their chemical nature based on the minute differences between individual bonds.

“Our team has developed several state-of-the-art techniques since 2009, which made this achievement possible,” said Dr. Niko Pavliček, a physicist at IBM Research – Zurich and lead author of the paper. “For this study, it was absolutely essential to pick an insulating film on which the molecules were adsorbed and to deliberately choose the atomic tip-terminations to probe them. We hope this technique will have profound effects on the future of chemistry and electronics.”

Prof. Peña, added that “These findings on arynes can be compared with the long-standing search for the giant squid. For centuries, fishermen had found clues of the existence of this legendary animal. But it was only very recently that scientists managed to film a giant squid alive. In both cases, state-of-the-art technologies were crucial to observe these elusive species alive: a low-noise submarine for the giant squid; a low-temperature AFM for the aryne.”

This research is part of IBM’s five-year, $3 billion investment to push the limits of chip technology and semiconductor innovations needed to meet the emerging demands of cloud computing and Big Data systems.

This work is a result of the large European project called (Planar Atomic and Molecular Scale Devices). PAMS’ main objective is to develop and investigate novel electronic devices of nanometric-scale size. Part of this research is also funded by a European Research Council Advanced Grant awarded to IBM scientist Gerhard Meyer, who is also a co-author of the paper.

Here’s a link to and a citation for the paper,

On-surface generation and imaging of arynes by atomic force microscopy by Niko Pavliček, Bruno Schuler, Sara Collazos, Nikolaj Moll, Dolores Pérez, Enrique Guitián, Gerhard Meyer, Diego Peña, & Leo Gross. Nature Chemistry (2015) doi:10.1038/nchem.2300 Published online 13 July 2015

This paper is behind a paywall.

Genes and jazz: a July 17, 2015 performance in Vancouver (Canada)

A geneticist and a jazz musician first combined forces for Genes and Jazz at a 2008 Guggenheim museum event where it was first conceptualized (and performed?). Vancouver will be lucky enough to enjoy a live performance on July 17, 2015 as part of the 2015 Indian Summer Festival (July 9 – 18, 2015). Here’s more from the festival event page,

What happens when you cross a Nobel prize-winning geneticist with one of New York’s most sought after jazz quintets? Genes & Jazz. Part jazz concert, part scientific talk by one of the world’s finest scientific minds, Genes & Jazz is where the seemingly dichotomous worlds of science and the arts meet.

Dr. Harold Varmus won the Nobel Prize in 1989 for his work on the proto-oncogene, which enhanced our understanding of cancer. [emphasis mine] His son, jazz trumpeter Jacob leads the Jacob Varmus Quintet. [emphasis mine] Together they explore the ways that genes and notes affect complex organisms and compelling music. The father-son duo compares cell biology to the development of musical compositions.

“Mutation is essential to species diversity just as stylistic variation is essential to the arts,” says Dr. Varmus. “Without genetic error, there would be no evolution. Without variety, there would be no development in art, literature or music. Variety is essential to progress.”

Genes & Jazz was sparked in 2008 as part of the ‘Works & Process’ series at the Guggenheim Museum in New York.

Logistics (from the ticket purchase page),

    July 17 – July 17 [2015]
Vancouver Playhouse
600 Hamilton Street at Dunsmuir
Vancouver, BC
Admission: $25 / $40 / $60

For anyone wondering about how the jazz might sound, there’s this from the ticket purchase page,

“…lyrical and self-assured, more Miles Davis than Dr. John.” – The New Yorker

I think the first  person to link jazz with biology was Dr. Mae-Won Ho in a 2006 Institute of Science in Society (ISIS) lecture: Quantum Jazz; the meaning of life, the universe, and everything (free version). The fully referenced and illustrated lecture is available for members only. Here’s an excerpt  from the lecture,

Quantum jazz is the music of the organism dancing life into being, from the top of her head to her toes and fingertips, every single cell, molecule and atom taking part in a remarkable ensemble that spins and sways to rhythms from pico (10-12) seconds to minutes, hours, a day, a month, a year and longer, emitting light and sound waves from atomic dimensions of nanometres up to metres, spanning a musical range of 70 octaves (for that is the range of living activities). And each and every player, the tinniest molecule not withstanding, is improvising spontaneously and freely, yet keeping in tune and in step with the whole.

There is no conductor, no choreographer, the organism is creating and recreating herself afresh with each passing moment.

That’s why ordinary folks like us can walk and chew gum at the same time, why top athletes can run a mile in under four minutes, and kung fu experts can move with lightning speed and perhaps even fly effortlessly through the air, like in the movie Crouching Tiger and Hidden Dragon. This perfect coordination of multiple tasks carried out simultaneously depends on a special state of wholeness or coherence best described as “quantum coherence”, hence quantum jazz.

Quantum coherent action is effortless action, effortless creation, the Taoist ideal of art and poetry, of life itself.

Dr. Ho also gave an interview about her influences and ‘quantum jazz’ which is reproduced in ISIS report 23/06/10 (presumably 23 June 2010),

ATHM [Alternative therapies in health and medicine]: Please tell us a little bit about your background and schooling.

Ho: I was born in Hong Kong; started school in Chinese and then transferred to an English school for girls, run by Italian nuns. I got exposed to serious Western ideas late-ish in life, when I was about 10 or 11 years old. I was quite good in school, and the nuns let me do whatever I liked; didn’t have to listen if I got bored. So I escaped the worst of reductionist Western education because ideas that didn’t fit just rolled off my back. I guess that explains why I’m always at odds with whatever the conventional theory is in every single field that I go into.

I was in the convent school until I entered Hong Kong University to read biology and then biochemistry as a PhD. Again, I learned almost nothing useful during that time. Maybe I exaggerate: I learned, by myself, of things I liked to learn about. After I finished university, I got a postdoctoral fellowship, and began to change fields because I didn’t like the kind of research I was doing. I began to revolt against neo-Darwinism and the reductionist way of looking at things in bits.

I had gone into biochemistry for my Ph.D. because of something I heard from one of the professors who quoted Albert St. Györgyi – the father of biochemistry—that life was interposed between two energy levels of an electron. I thought that was sheer poetry. That made me want to know, “what is life?”

So I went into biochemistry thinking I would find the answer there. But it was very dull because biochemistry then was about cutting up and grinding up everything, separating, purifying. Nothing to tell you about what life is about.

Biology as a whole was studying dead, pinned specimens. There was nothing that answered the question, what is biological organization? What makes organisms tick? What is being alive? I especially detested neo-Darwinism because it was the most mind-numbing theory that purports to explain anything and everything by “selective advantage”, competition and selective advantage.

I spent a lot of time criticizing neo-Darwinism until I got bored. What neo-Darwinism leaves out is the whole of chemistry, physics, and mathematics, all science in fact. You don’t even need any physiology or developmental biology if everything can be explained in terms of selective advantage and a gene for any and every character, real or imaginary.

Finally, I met some remarkable people and learned a lot from them, and completely changed my field of research to try and answer that haunting question, “what is life?” I wrote a book on the ‘physics of organisms’, not ‘biophysics’, which is largely about the structure of dead biological materials and physical methods used in characterizing them. The physics of organisms is about living organization, quantum coherence and other important concepts.

Varmus and Ho may or may not be familiar with each other’s work linking jazz with biology. It wouldn’t be the first time that two or more people came to similar conclusions without reference to each other. At a guess, I’d say Ho’s approach is more about the poetry or the metaphor while Varmus’ approach is more about the music.

Superposition in biological processes

Applying the concept of superposition to photosynthesis and olfaction is not the first thought that would have occurred to me on stumbling across the European Union’s PAPETS project (Phonon-Assisted Processes for Energy Transfer and Sensing). Thankfully, a July 9, 2015 news item on Nanowerk sets the record straight (Note: A link has been removed),

Quantum physics is helping researchers to better understand photosynthesis and olfaction.

Can something be for instance in two different places at the same time? According to quantum physics, it can. More precisely, in line with the principle of ‘superposition’, a particle can be described as being in two different states simultaneously.

While it may sound like voodoo to the non-expert, superposition is based on solid science. Researchers in the PAPETS project are exploring this and other phenomena on the frontier between biology and quantum physics. Their goal is to determine the role of vibrational dynamics in photosynthesis and olfaction.

A July 7, 2015 research news article on the CORDIS website, which originated the news item, further explains (Note: A link has been removed),

Quantum effects in a biological system, namely in a photosynthetic complex, were first observed by Greg Engel and collaborators in 2007, in the USA. These effects were reproduced in different laboratories at a temperature of around -193 degrees Celsius and subsequently at ambient temperature.

‘What’s surprising and exciting is that these quantum effects have been observed in biological complexes, which are large, wet and noisy systems,’ says PAPETS project coordinator, Dr. Yasser Omar, researcher at Instituto de Telecomunicações and professor at Universidade de Lisboa [Portugal]. ‘Superposition is fragile and we would expect it to be destroyed by the environment.’

Superposition contributes to more efficient energy transport. An exciton, a quantum quasi-particle carrying energy, can travel faster along the photosynthetic complex due to the fact that it can exist in two states simultaneously. When it comes to a bifurcation it need not choose left or right. It can proceed down both paths simultaneously.

‘It’s like a maze,’ says Dr. Omar. ‘Only one door leads to the exit but the exciton can probe both left and right at the same time. It’s more efficient.’

Dr. Omar and his colleagues believe that a confluence of factors help superposition to be effected and maintained, namely the dynamics of the vibrating environment, whose role is precisely what the PAPETS project aims to understand and exploit.

Theory and experimentation meet

The theories being explored by PAPETS are also tested in experiments to validate them and gain further insights. To study quantum transport in photosynthesis, for example, researchers shoot fast laser pulses into biological systems. They then observe interference along the transport network, a signature of wavelike phenomena.

‘It’s like dropping stones into a lake,’ explains Dr. Omar. ‘You can then see whether the waves that are generated grow bigger or cancel each other when they meet.’

Applications: more efficient solar cells and odour detection

While PAPETS is essentially an exploratory project, it is generating insights that could have practical applications. PAPETS’ researchers are getting a more fundamental understanding of how photosynthesis works and this could result in the design of much more efficient solar cells.

Olfaction, the capacity to recognise and distinguish different odours, is another promising area. Experiments focus on the behaviour of Drosophila flies. So far, researchers suspect that the tunnelling of electrons associated to the internal vibrations of a molecule may be a signature of odour. Dr. Omar likens this tunnelling to a ping-pong ball resting in a bowl that goes through the side of the bowl to appear outside it.

This work could have applications in the food, water, cosmetics or drugs industries. Better artificial odour sensing could be used to detect impurities or pollution, for example.

‘Unlike seeing, hearing or touching, the sense of smell is difficult to reproduce artificially with high efficacy,’ says Dr. Omar.

The PAPETS project, involving 7 partners, runs from September 2014 to August 2016 and has a budgeted EU contribution funding of EUR 1.8 million.

You can find out more about PAPETS here. In the meantime, I found the other partners in the project (in addition to Portugal), from the PAPETS Partners webpage (Note: Links have been removed),

– Controlled Quantum Dynamics Group, Universität Ulm (UULM), Germany. PI: Martin Plenio and Susana Huelga.
– Biophysics Research Group, Vrije Universiteit Amsterdam (VUA), Netherlands. PI: Rienk van Grondelle and Roberta Croce.
– Department of Chemical Sciences, Università degli Studi di Padova (UNIPD), Italy. PI: Elisabetta Collini.
– Biomedical Sciences Research Centre “Alexander Fleming” (FLEMING), Athens, Greece. PI: Luca Turin and Efthimios M. Skoulakis.
– Biological Physics and Complex Systems Group, Centre National de la Recherche Scientifique (CNRS), Orléans, France. PI: Francesco Piazza.
– Quantum Physics of Biomolecular Processes, University College London (UCL), UK. PI: Alexandra Olaya-Castro.

Brain data (neuroscience) crowdsourced at Toronto’s (Canada) 2013 Nuit Blanche event

The brain data was crowdsourced in 2013 in Toronto but only recently published according to a July 8, 2015 Baycrest Centre for Geriatric Care news release (also on EurekAlert),

Neuroscientists in Toronto have shown that crowdsourcing brain data with hundreds of adults in a short period of time could be a new frontier in neuroscience and lead to new insights about the brain.

More than 500 adults aged 18 and older participated in the experiment at the 2013 Scotiabank Nuit Blanche arts event in Toronto. Baycrest, in partnership with the University of Toronto and industry partners, created a large-scale art-science installation called My Virtual Dream. Festival-goers were invited to wear a Muse™ wireless electroencephalography (EEG) headband and participate in a brief collective neurofeedback experience in groups of 20 inside a 60-foot geodesic dome. The group’s collective EEG signals triggered a specific catalogue of artistic imagery displayed on the dome’s 360-degree interior, along with spontaneous musical interpretation by live musicians on stage.

The installation was one of the most popular at Nuit Blanche, with an average lineup wait time of two hours.

Studying brains in a social and multi-sensory environment is closer to real life and may help scientists to approach questions of complex real-life social cognition that otherwise are not accessible in traditional labs that study one person’s cognitive functions at a time.

“In traditional lab settings, the environment is so controlled that you can lose some of the fine points of real-time brain activity that occur in a social life setting,” said Dr. Kovacevic, creative producer of My Virtual Dream and program manager of the Centre for Integrative Brain Dynamics at Baycrest’s Rotman Research Institute.

“What we’ve done is taken the lab to the public. We collaborated with multi-media artists, made this experiment incredibly engaging, attracted highly motivated subjects which is not easy to do in the traditional lab setting, and collected useful scientific data from their experience.”

Results from the experiment not only demonstrated the scientific viability of collective neurofeedback as a potential new avenue of neuroscience research that takes into account individuality, complexity and sociability of the human mind, but yielded new evidence that neurofeedback learning can have an effect on the brain almost immediately.

Neurofeedback learning supports mindful awareness and joins a growing market for wearable biofeedback devices. The device used in this study, Muse™, is a clinical-grade EEG brain computer interface (BCI) headband that helps individuals to be more aware of their brain states (relaxed versus focused versus distracted) and learn self-regulation of brain function to fit their personal goals.

A total of 523 adults (209 males, 314 females), ranging in age from 18 to 89, with an average age of 31, contributed their EEG brain data for the study. Each session involved 20 participants being seated in a semicircle in front of a stage and divided into four groups (“pods”) of five. They played a collective neurofeedback computer game where they were required to manipulate their mental states of relaxation and concentration. The neurofeedback training lasted 6.5 minutes, which is much shorter than typical neurofeedback training experiments.

The massive amount of EEG data collected in one night yielded an interesting and statistically relevant finding – that subtle brain activity changes were taking place within approximately one minute of the neurofeedback learning exercise – unprecedented speed of learning changes that have not been demonstrated before.

“These results really open up a whole new domain of neuroscience study that actively engages the public to advance our understanding of the brain,” said Dr. Randy McIntosh, director of the Rotman Research Institute and vice-president of Research at Baycrest. He is a senior author on the paper.

The idea for the Nuit Blanche art -science experiment was inspired by Baycrest’s ongoing international project to build the world’s first functional, virtual brain – a research and diagnostic tool that could one day revolutionize brain healthcare.

Baycrest cognitive neuroscientists collaborated with artists and gaming and wearable technology industry partners for over a year to create the My Virtual Dream installation. Partners included the University of Toronto, Scotiabank Nuit Blanche, Muse™ and Uken Games.

Here’s a link to and a citation for the paper,

‘My Virtual Dream’: Collective Neurofeedback in an Immersive Art Environment by Natasha Kovacevic, Petra Ritter, William Tays, Sylvain Moreno, and Anthony Randal McIntosh. DOI: 10.1371/journal.pone.0130129 PLOS Published: July 8, 2015

This is an open access paper.

A few final words, I last wrote about MUSE (a Canadian technology company) in a March 6, 2015 posting. Uken Games , also a Canadian company, is new to this blog.

Repeating patterns: earth’s daily rotation cycle seen in protein

This story made me think of fractals where a pattern at one scale is repeated at a smaller scale. Here’s more about the earth’s rotation and the protein from a June 25, 2015 news item on ScienceDaily,

A collaborative group of Japanese researchers has demonstrated that the Earth’s daily rotation period (24 hours) is encoded in the KaiC protein at the atomic level, a small, 10 nm-diameter biomolecule expressed in cyanobacterial cells.

For anyone who’s unfamiliar (me) with cyanobacteria, here’s a definition from its Wikipedia entry (Note: Links have been removed),

Cyanobacteria /saɪˌænoʊbækˈtɪəriə/, also known as Cyanophyta, is a phylum of bacteria that obtain their energy through photosynthesis.[3] The name “cyanobacteria” comes from the color of the bacteria (Greek: κυανός (kyanós) = blue). They are often called blue-green algae (but some consider that name a misnomer, as cyanobacteria are prokaryotic and algae should be eukaryotic,[4] although other definitions of algae encompass prokaryotic organisms).[5]

By producing gaseous oxygen as a byproduct of photosynthesis, cyanobacteria are thought to have converted the early reducing atmosphere into an oxidizing one, causing the “rusting of the Earth”[6] and dramatically changing the composition of life forms on Earth by stimulating biodiversity and leading to the near-extinction of oxygen-intolerant organisms. According to endosymbiotic theory, the chloroplasts found in plants and eukaryotic algae evolved from cyanobacterial ancestors via endosymbiosis.

The idea that cyanobacteria may have changed the earth’s atmosphere into an oxidizing one and stimulating biodiversity is fascinating to me. Plus, cyanobacteria are pretty,

    CC BY-SA 3.0     File:Tolypothrix (Cyanobacteria).JPG     Uploaded by Matthewjparker     Created: January 22, 2013     Location: 29° 38′ 58.2″ N, 82° 20′ 40.8″ W [downloaded from https://en.wikipedia.org/wiki/Cyanobacteria]

CC BY-SA 3.0
File:Tolypothrix (Cyanobacteria).JPG
Uploaded by Matthewjparker
Created: January 22, 2013
Location: 29° 38′ 58.2″ N, 82° 20′ 40.8″ W [downloaded from https://en.wikipedia.org/wiki/Cyanobacteria]

A June 26, 2015 Japan National Institute of Natural Sciences, which originated the news item, provides more information,

The results of this joint research will help elucidate a longstanding question in chronobiology: How is the circadian period of biological clocks determined? The results will also help understand the basic molecular mechanism of the biological clock. This knowledge might contribute to the development of therapies for disorders associated with abnormal circadian rhythms.

The results will be disclosed online on June 25, 2015 (North American Eastern Standard Time) in ScienceExpress, the electronic version of Science, published by the American Association for the Advancement of Science (AAAS).
1. Research Background

In accordance with diurnal changes in the environment (notably light intensity and temperature) resulting from the Earth’s daily rotation around its axis, many organisms regulate their biological activities to ensure optimal fitness and efficiency. The biological clock refers to the mechanism whereby organisms adjust the timing of their biological activities. The period of this clock is set to approximately 24 hours. A wide range of studies have investigated the biological clock in organisms ranging from bacteria to mammals. Consequently, the relationship between the biological clock and multiple diseases has been clarified. However, it remains unclear how 24-hour circadian rhythms are implemented.

The research group mentioned above addressed this question using cyanobacteria. The cyanobacterial circadian clock can be reconstructed by mixing three clock proteins (KaiA, KaiB, and KaiC) and ATP. A study published in 2007 showed that KaiC ATPase activity, which mediates the ATP hydrolysis reaction, is strongly associated with circadian periodicity. The results of that study indicated that the functional structure of KaiC could be responsible for determining the circadian rhythm.

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Figure 1  Earth and the circadian clock protein KaiC
2. Research Results

KaiC ATPase activity exhibits a robust circadian oscillation in the presence of KaiA and KaiB proteins (Figure 2). In the study reported here, the temporal profile of KaiC ATPase activity exhibited an attenuating and oscillating component even in the absence of KaiA and KaiB. A close analysis revealed that this signal had a frequency of 0.91 day-1, which approximately coincided with the 24-hour period. Thus, KaiC is the source of a steady cycle that is in tune with the Earth’s daily rotation.
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Figure 2  KaiC ATPase activity-time profile
To identify causal structural factors, the N-terminal domain of KaiC was analyzed using high-resolution crystallography. The resultant atomic structures revealed the underlying cause of KaiC’s slowness relative to other ATPases (Figure 3). “A water molecule is prevented from attacking into the ideal position (a black dot in Figure 3) for the ATP hydrolysis by a steric hindrance near ATP phosphoryl groups. In addition, this hindrance is surely anchored to a spring-like structure derived from polypeptide isomerization,” elaborates Dr. Jun Abe. “The ATP hydrolysis, which involves access of a water molecule to the bound ATP and reverse isomerization of the polypeptide, is expected to require a significantly larger amount of free energy than for typical ATP hydrolysis. Thus, the three-dimensional atomic structure discovered in this study explains why the ATPase activity of KaiC is so much lower (by 100- to 1,000,000-fold) than that of typical ATPase molecules.”

150626_en3.jpgFigure 3  Structural basis for steady slowness. The steric barrier prevents access of a water molecule to the catalytic site (indicated by a black dot).

The circadian clock’s period is independent of ambient temperature, a phenomenon known as temperature compensation. One KaiC molecule is composed of six identical subunits, each containing duplicated domains with a series of ATPase motifs. The asymmetric atomic-scale regulation by the aforementioned mechanism dictates a feedback mechanism that maintains the ATPase activity at a constant low level. The authors of this study discovered that the Earth’s daily rotation period (24 hours) is implemented as the time constant of the feedback mechanism mediated in this protein structure.

3. Technological Implications

KaiC and other protein molecules are capable of moving on short time scales, on the order of 10-12 to 10-1 seconds. This study provides the first atomic-level demonstration that small protein molecules can generate 24-hour rhythms by regulating molecular structure and reactivity. Lab head and CIMoS Director Prof. Shuji Akiyama sees, “The fact that a water molecule, ATP, the polypeptide chain, and other universal biological components are involved in this regulation suggests that humans and other complex organisms may also share a similar molecular machinery. In the crowded intracellular environment that contains a myriad of molecular signals, KaiC demonstrates long-paced oscillations using a small amount of energy generated through ATP consumption. This clever mechanism for timekeeping in a noisy environment may inspire development of highly efficient and sustainable chemical reaction processes and molecular-system-based information processing.”
4. Glossary

1) Clock protein
A clock protein plays an essential role in the circadian pacemaker. Mutations and deficiencies in clock proteins can alter the intrinsic characteristics of circadian rhythm.

2) ATP
Adenosine triphosphate is a source of energy required for muscle contraction and many other biological activities. ATP, a nucleotide that mediates the storage and consumption of energy, is sometimes referred to as the “currency of biological energy” due to its universality and importance in metabolism. ATP consists of an adenosine molecule bound to three phosphate groups. Upon hydrolysis, the ATPase releases one phosphate molecule plus approximately 8 kcal/mol of energy.

3) Polypeptide isomerization
Protein polypeptide main chains undergo isomerization on a time scale of seconds or longer; therefore, protein isomerization is one of the slowest biological reactions. Most functional protein main chains have a trans conformation, and a few proteins have a functional cis conformation.

Here’s a link to and a citation for the paper,

Atomic-scale origins of slowness in the cyanobacterial circadian clock by Jun Abe, Takuya B. Hiyama, Atsushi Mukaiyama, Seyoung Son, Toshifumi Mori, Shinji Saito, Masato Osako, Julie Wolanin, Eiki Yamashita, Takao Kondo, & Shuji Akiyama. Science DOI: 10.1126/science.1261040 Published Online June 25 2015 (on Science Express)

This paper is behind a paywall.

Kudos to the person(s) who wrote the news release.

A pragmatic approach to alternatives to animal testing

Retitled and cross-posted from the June 30, 2015 posting (Testing times: the future of animal alternatives) on the International Innovation blog (a CORDIS-listed project dissemination partner for FP7 and H2020 projects).

Maryse de la Giroday explains how emerging innovations can provide much-needed alternatives to animal testing. She also shares highlights of the 9th World Congress on Alternatives to Animal Testing.

‘Guinea pigging’ is the practice of testing drugs that have passed in vitro and in vivo tests on healthy humans in a Phase I clinical trial. In fact, healthy humans can make quite a bit of money as guinea pigs. The practice is sufficiently well-entrenched that there is a magazine, Guinea Pig Zero, devoted to professionals. While most participants anticipate some unpleasant side effects, guinea pigging can sometimes be a dangerous ‘profession’.

HARMFUL TO HEALTH

One infamous incident highlighting the dangers of guinea pigging occurred in 2006 at Northwick Park Hospital outside London. Volunteers were offered £2,000 to participate in a Phase I clinical trial to test a prospective treatment – a monoclonal antibody designed for rheumatoid arthritis and multiple sclerosis. The drug, called TGN1412, caused catastrophic systemic organ failure in participants. All six individuals receiving the drug required hospital treatment. One participant reportedly underwent amputation of fingers and toes. Another reacted with symptoms comparable to John Merrick, the Elephant Man.

The root of the disaster lay in subtle immune system differences between humans and cynomolgus monkeys – the model animal tested prior to the clinical trial. The drug was designed for the CD28 receptor on T cells. The monkeys’ receptors closely resemble those found in humans. However, unlike these monkeys, humans have other immune cells that carry CD28. The trial participants received a starting dosage that was 0.2 per cent of what the monkeys received in their final tests, but failure to take these additional receptors into account meant a dosage that was supposed to occupy 10 per cent of the available CD28 receptors instead occupied 90 per cent. After the event, a Russian inventor purchased the commercial rights to the drug and renamed it TAB08. It has been further developed by Russian company, TheraMAB, and TAB08 is reportedly in Phase II clinical trials.

HUMAN-ON-A-CHIP AND ORGANOID PROJECTS

While animal testing has been a powerful and useful tool for determining safe usage for pharmaceuticals and other types of chemicals, it is also a cruel and imperfect practice. Moreover, it typically only predicts 30-60 per cent of human responses to new drugs. Nanotechnology and other emerging innovations present possibilities for reducing, and in some cases eliminating, the use of animal models.

People for the Ethical Treatment of Animals (PETA), still better known for its publicity stunts, maintains a webpage outlining a number of alternatives including in silico testing (computer modelling), and, perhaps most interestingly, human-on-a-chip and organoid (tissue engineering) projects.

Organ-on-a-chip projects use stem cells to create human tissues that replicate the functions of human organs. Discussions about human-on-a-chip activities – a phrase used to describe 10 interlinked organ chips – were a highlight of the 9th World Congress on Alternatives to Animal Testing held in Prague, Czech Republic, last year. One project highlighted at the event was a joint US National Institutes of Health (NIH), US Food and Drug Administration (FDA) and US Defense Advanced Research Projects Agency (DARPA) project led by Dan Tagle that claimed it would develop functioning human-on-a-chip by 2017. However, he and his team were surprisingly close-mouthed and provided few details making it difficult to assess how close they are to achieving their goal.

By contrast, Uwe Marx – Leader of the ‘Multi-Organ-Chip’ programme in the Institute of Biotechnology at the Technical University of Berlin and Scientific Founder of TissUse, a human-on-a-chip start-up company – claims to have sold two-organ chips. He also claims to have successfully developed a four-organ chip and that he is on his way to building a human-on-a-chip. Though these chips remain to be seen, if they are, they will integrate microfluidics, cultured cells and materials patterned at the nanoscale to mimic various organs, and will allow chemical testing in an environment that somewhat mirrors a human.

Another interesting alternative for animal testing is organoids – a feature in regenerative medicine that can function as test sites. Engineers based at Cornell University recently published a paper on their functional, synthetic immune organ. Inspired by the lymph node, the organoid is comprised of gelatin-based biomaterials, which are reinforced with silicate nanoparticles (to keep the tissue from melting when reaching body temperature) and seeded with cells allowing it to mimic the anatomical microenvironment of a lymphatic node. It behaves like its inspiration converting B cells to germinal centres which activate, mature and mutate antibody genes when the body is under attack. The engineers claim to be able to control the immune response and to outperform 2D cultures with their 3D organoid. If the results are reproducible, the organoid could be used to develop new therapeutics.

Maryse de la Giroday is a science communications consultant and writer.

Full disclosure: Maryse de la Giroday received transportation and accommodation for the 9th World Congress on Alternatives to Animal Testing from SEURAT-1, a European Union project, making scientific inquiries to facilitate the transition to animal testing alternatives, where possible.

ETA July 1, 2015: I would like to acknowledge more sources for the information in this article,

Sources:

The guinea pigging term, the ‘professional aspect, the Northwick Park story, and the Guinea Pig Zero magazine can be found in Carl Elliot’s excellent 2006 story titled ‘Guinea-Pigging’ for New Yorker magazine.

http://www.newyorker.com/magazine/2008/01/07/guinea-pigging

Information about the drug used in the Northwick Park Hospital disaster, the sale of the rights to a Russian inventor, and the June 2015 date for the current Phase II clinical trials were found in this Wikipedia essay titled, TGN 1412.

http://en.wikipedia.org/wiki/TGN1412

Additional information about the renamed drug, TAB08 and its Phase II clinical trials was found on (a) a US government website for information on clinical trials, (b) in a Dec. 2014 (?) TheraMAB  advertisement in a Nature group magazine and a Jan. 2014 press release,

https://www.clinicaltrials.gov/ct2/show/NCT01990157?term=TAB08_RA01&rank=1

http://www.theramab.ru/TheraMAB_NAture.pdf

http://theramab.ru/en/news/phase_II

An April 2015 article (Experimental drug that injured UK volunteers resumes in human trials) by Owen Dyer for the British Medical Journal also mentioned the 2015 TheraMab Phase II clinical trials and provided information about the information about Macaque (cynomolgus) monkey tests.

http://www.bmj.com.proxy.lib.sfu.ca/content/350/bmj.h1831

BMJ 2015; 350 doi: http://dx.doi.org.proxy.lib.sfu.ca/10.1136/bmj.h1831 (Published 02 April 2015) Cite this as: BMJ 2015;350:h1831

A 2009 study by Christopher Horvath and Mark Milton somewhat contradicts the Dyer article’s contention that a species Macaque monkey was used as an animal model. (As the Dyer article is more recent and the Horvath/Milton analysis is more complex covering TGN 1412 in the context of other MAB drugs and their precursor tests along with specific TGN 1412 tests, I opted for the simple description.)

The TeGenero Incident [another name for the Northwick Park Accident] and the Duff Report Conclusions: A Series of Unfortunate Events or an Avoidable Event? by Christopher J. Horvath and Mark N. Milton. Published online before print February 24, 2009, doi: 10.1177/0192623309332986 Toxicol Pathol April 2009 vol. 37 no. 3 372-383

http://tpx.sagepub.com/content/37/3/372.full

Philippa Roxbuy’s May 24, 2013 BBC news online article provided confirmation and an additional detail or two about the Northwick Park Hospital accident. It notes that other models, in addition to animal models, are being developed.

http://www.bbc.com/news/health-22556736

Anne Ju’s excellent June 10,2015 news release about the Cornell University organoid (synthetic immune organ) project was very helpful.

http://www.news.cornell.edu/stories/2015/06/engineers-synthetic-immune-organ-produces-antibodies

There will also be a magazine article in International Innovation, which will differ somewhat from the blog posting, due to editorial style and other requirements.

ETA July 22, 2015: I now have a link to the magazine article.