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Topping out for new engineering hub at the University of Cambridge

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Tom Dyson, James Dyson’s brother, fulfilled the duty by pouring a bottle of Elgoods Cambridge Bitter onto the roof to mark the event.

He was supported by Bob Ensch, Area Managing Director for Morgan Sindall, the main contractor for the new £13.3 million development, and Angus Stephen, Operations Director for the University’s Estate Management.

The building was made possible by a £6million donation from the James Dyson Foundation. The Foundation has also funded the development of a design centre for undergraduate engineering students.

The James Dyson Building for Engineering will house postgraduates and support world leading research in areas including advanced materials, smart infrastructure, electric vehicles, and efficient internal combustion systems for cars.

The building has a central nervous system of sensors built into it, giving those working inside it a chance to use their surroundings for research and teaching.

Specialist knowledge on research strategies and funding advice will be available on-site, supported by Philip Guildford Director of Research at the Department of Engineering.

Research undertaken in the hub will build on a rich tradition of invention: it was at Cambridge that Harry Riccardo pioneered the internal combustion engine and Frank Whittle revolutionised travel with his jet engine invention.

The Department is located at the heart of the Cambridge cluster, which has created over 1,500 spin-out companies over the last decade.

Technology we take for granted, including: Concorde ‘droop’ nose design, the microchips developed by ARM that now power 90% of the world’s mobile phones, and the pregnancy test.

James Dyson said: “Developing the intellectual property that will help Britain succeed in the global technology race depends on applying our brightest minds to ambitious and exciting research projects. I’m hopeful that this new space for Britain’s best engineers at the University of Cambridge will catalyse great technological breakthroughs that transform how we live”.

A topping out ceremony has been held for the James Dyson Building for Engineering in central Cambridge.

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Yes

Calls vs. balls: monkeys with more impressive roars produce less sperm

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Howler monkeys are about the size of a small dog, weighing around seven kilos, yet they are among the loudest terrestrial animals on the planet, and can roar at a similar acoustic frequency to tigers.

Evolution has given these otherwise lethargic creatures a complex and powerful vocal system. For males, a critical function of the roar is for mating: to attract females and scare off rival males.

But not all male howler monkeys have been equally endowed. New research on howler species has revealed an evolutionary “trade-off” between investments in the size of the male hyoid – the bulbous, hollow throat bone that allows the howlers’ guttural roar to resonate – and in the size of reproductive organs, namely the testes.

The bigger a male howler’s vocal organ, and the deeper and more imposing roar they possess, the smaller their testes and the less sperm they can produce.  

Researchers found that the trade-off corresponds to the mating systems of different howler species. Males with large hyoids and deeper roars but more diminutive testes live in small social groups with often only one male dominating a number of females – a “harem” social model.

Males with bigger testes and smaller hyoids live in large groups with up to five or six males, and females mate with all males in the group. These males don’t have exclusive access to females, and the battle for reproduction is geared more towards “sperm competition”: quantity and quality of sperm.  

The findings, published today in the journal Current Biology, are a further example of sexual selection say the researchers – a theory first proposed by Charles Darwin in 1871 – and in particular the evolutionary trade-off between “pre- and post-copulatory reproductive strategies”: traits that help males compete for access to mates versus those that help males compete to fertilise eggs.

“In evolutionary terms, all males strive to have as many offspring as they can, but when it comes to reproduction you can’t have everything,” said Dr Jacob Dunn, from the University of Cambridge’s Division of Biological Anthropology, who led the new study.

“There is evidence in other animals that when males invest in large bodies, bright colours, or weaponry such as horns or long canines, they are unable to also invest in reproductive traits. However, this is the first evidence in any species for a trade-off between vocal investment and sperm production,” he said.

In biology, trade-offs are said to exist when one trait cannot increase without a decrease in another. However, Dunn says that it’s not yet clear exactly how the evolutionary trade-off in male howler monkeys works.

“It may be that investment in developing a large vocal organ and roaring is so costly that there is simply not enough energy left to invest in testes. Alternatively, using a large vocal organ for roaring may be so effective at deterring rival males that there is no need to invest in large testes,” he said.  

Along with collecting data on the average testes size across howler species, the researchers also used 3-D laser scans to analyse the size of over 250 hyoids – finding a ten-fold variation from the smallest to the largest howler throat bone. The team also conducted in-depth acoustic analyses of a number of howler roars.

“The vocal folds of a howler monkey are three times longer than a human’s, yet they are ten times smaller than us, with a hyoid bone uniquely adapted to resonate sound and exaggerate their size,” said Dunn.

“The results of our acoustic analyses show that howler monkeys produce roars at a similar frequency as tigers, which is far lower than we would have predicted from their body size, yet exactly what would be predicted from measuring their giant vocal folds.”

This vocal system means that howlers give the acoustic impression of animals with much larger bodies, and can indeed roar louder and deeper than creatures ten times their size. The unnerving sound of a howler chorus ringing out across forests of Central and South America has long fascinated humans – from ancient Mayans to modern primatologists – and can carry as far as five kilometres through dense rainforest.   

Charles Darwin was fascinated by the “wonderfully powerful” vocal organs of the howler monkey, despite describing their chorus as a “dreadful concert” in The Descent of Man.

The new Cambridge research continues to show just how accurate Darwin was when he wrote in On the Origin of Species: “The whole organism is so tied together that when slight variations in one part occur, and are accumulated through natural selection, other parts become modified.”

Evolutionary ‘trade-off’ between size of throat and testes discovered in howler monkeys furthers Darwin’s theory of sexual selection and corresponds to mating systems: males with larger throats but smaller testes often have exclusive access to females, while those with larger testes share mates.    

In evolutionary terms, all males strive to have as many offspring as they can, but when it comes to reproduction you can’t have everything
Jacob Dunn
A black howler monkey chorus

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Yes

Plague in humans ‘twice as old’ but didn’t begin as flea-borne, ancient DNA reveals

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New research using ancient DNA has revealed that plague has been endemic in human populations for more than twice as long as previously thought, and that the ancestral plague would have been predominantly spread by human-to-human contact – until genetic mutations allowed Yersinia pestis (Y. pestis), the bacteria that causes plague, to survive in the gut of fleas.

These mutations, which may have occurred near the turn of the 1st millennium BC, gave rise to the bubonic form of plague that spreads at terrifying speed through flea – and consequently rat – carriers. The bubonic plague caused the pandemics that decimated global populations, including the Black Death, which wiped out half the population of Europe in the 14th century.  

Before its flea-borne evolution, however, researchers say that plague was in fact endemic in the human populations of Eurasia at least 3,000 years before the first plague pandemic in historical records (the Plague of Justinian in 541 AD).

They say the new evidence that Y. pestis bacterial infection in humans actually emerged around the beginning of the Bronze Age suggests that plague may have been responsible for major population declines believed to have occurred in the late 4th and early 3rd millennium BC.   

The work was conducted by an international team including researchers from the universities of Copenhagen, Denmark, and Cambridge, UK, and the findings are published today in the journal Cell

“We found that the Y. pestis lineage originated and was widespread much earlier than previously thought, and we narrowed the time window as to when and how it developed,” said senior author Professor Eske Willerslev, who recently joined Cambridge University’s Department of Zoology from the University of Copenhagen. 

“The underlying mechanisms that facilitated the evolution of Y. pestis are present even today. Learning from the past may help us understand how future pathogens may arise and evolve,” he said.

Researchers analysed ancient genomes extracted from the teeth of 101 adults dating from the Bronze Age and found across the Eurasian landmass.

They found Y. pestis bacteria in the DNA of seven of the adults, the oldest of whom died 5,783 years ago – the earliest evidence of plague. Previously, direct molecular evidence for Y. pestis had not been obtained from skeletal material older than 1,500 years.  

However, six of the seven plague samples were missing two key genetic components found in most modern strains of plague: a “virulence gene” called ymt, and a mutation in an “activator gene” called pla.

The ymt gene protects the bacteria from being destroyed by the toxins in flea guts, so that it multiplies, choking the flea’s digestive tract. This causes the starving flea to frantically bite anything it can, and, in doing so, spread the plague.

The mutation in the pla gene allows Y. pestis bacteria to spread across different tissues, turning the localised lung infection of pneumonic plague into one of the blood and lymph nodes.

Researchers concluded these early strains of plague could not have been carried by fleas without ymt. Nor could they cause bubonic plague – which affects the lymphatic immune system, and inflicts the infamous swollen buboes of the Black Death – without the pla mutation.

Consequently, the plague that stalked populations for much of the Bronze Age must have been pneumonic, which directly affects the respiratory system and causes desperate, hacking coughing fits just before death. Breathing around infected people leads to inhalation of the bacteria, the crux of its human-to-human transmission.   

Study co-author Dr Marta Mirazón-Lahr, from Cambridge’s Leverhulme Centre for Human Evolutionary Studies (LCHES), points out that a study earlier this year from Willerslev’s Copenhagen group showed the Bronze Age to be a highly active migratory period, which could have led to the spread of pneumonic plague.

“The Bronze Age was a period of major metal weapon production, and it is thought increased warfare, which is compatible with emerging evidence of large population movements at the time. If pneumonic plague was carried as part of these migrations, it would have had devastating effects on small groups they encountered,” she said.   

“Well-documented cases have shown the pneumonic plague’s chain of infection can go from a single hunter or herder to ravaging an entire community in two to three days.”

The most recent of the seven ancient genomes to reveal Y. pestis in the new study has both of the key genetic mutations, indicating an approximate timeline for the evolution that spawned flea-borne bubonic plague.

“Among our samples, the mutated plague strain is first observed in Armenia in 951 BC, yet is absent in the next most recent sample from 1686 BC – suggesting bubonic strains evolve and become fixed in the late 2nd and very early 1st millennium BC,” said Mirazón-Lahr.

“However, the 1686 BC sample is from the Altai mountains near Mongolia. Given the distance between Armenia and Altai, it’s also possible that the Armenian strain of bubonic plague has a longer history in the Middle East, and that historical movements during the 1st millennium BC exported it elsewhere.”

The Books of Samuel in the Bible describe an outbreak of plague among the Philistines in 1320 BC, complete with swellings in the groin, which the World Health Organization has argued fits the description of bubonic plague. Mirazón-Lahr suggests this may support the idea of a Middle Eastern origin for the plague’s highly lethal genetic evolution.

Co-author Professor Robert Foley, also from Cambridge’s LCHES, suggests that the lethality of bubonic plague may have required the right population demography before it could thrive. 

“Every pathogen has a balance to maintain. If it kills a host before it can spread, it too reaches a ‘dead end’. Highly lethal diseases require certain demographic intensity to sustain them.

“The endemic nature of pneumonic plague was perhaps more adapted for an earlier Bronze Age population. Then, as Eurasian societies grew in complexity and trading routes continued to open up, maybe the conditions started to favour the more lethal form of plague,” Foley said.  

“The Bronze Age is the edge of history, and ancient DNA is making what happened at this critical time more visible,” he said.

Willerslev added: “These results show that the ancient DNA has the potential not only to map our history and prehistory, but also discover how disease may have shaped it.”

Inset image: An SEM micrograph depicting a mass of Y. pestis bacteria in the foregut of an infected flea.

New research dates plague back to the early Bronze Age, showing it had been endemic in humans across Eurasia for millennia prior to first recorded global outbreak, and that ancestral plague mutated into its bubonic, flea-borne form between the 2nd and 1st millennium BC.

These results show that the ancient DNA has the potential not only to map our history and prehistory, but also discover how disease may have shaped it
Eske Willerslev
Left: Skull of a Yamnaya, the people who migrated to Central Asia in early Bronze Age and developed the Afanasievo culture. The Afanasievo are one of the Bronze Age groups carrying Y. pestis. Right: Scanning Electron Micrograph Of A Flea

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Yes

New partnerships for ‘low carbon cities’ in the UK and China

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The projects will receive over £3 million in funding from the UK’s Engineering and Physical Sciences Research Council (EPSRC), with matched equivalent resources from the National Natural Science Foundation of China (NSFC).

Funded under the Low Carbon Cities programme, the projects will encourage collaboration between leading UK and Chinese academics, combining research to reduce the carbon emissions of existing technologies.

The projects will also deliver fundamental research into alternative energy sources and a reduction of energy demand, all with a focus on future urban environments.

By using comparative research to examine social, political and technical challenges, this will help the UK and China to successfully transition towards future low carbon cities. This programme and joint funding process has been facilitated by the RCUK China office.

“The aim of this UK-China research collaboration will be to reduce worldwide CO2 production and ensure energy security and affordability,” said Professor Philip Nelson FREng, EPSRC’s Chief Executive. “This is the first of three low carbon innovation projects between EPSRC and NSFC. The projects build on the strength of our internationally renowned research and will benefit both the UK and Chinese economies.”

“NSFC has been working closely with EPSRC for several years to address challenges related to achieving a low-carbon economy,” said Professor Che Chengwei, Deputy Director General, Department of Engineering and Material Sciences, NSFC. “This latest programme, with a focus on future urban environments, will build substantially stronger links between Chinese and UK research communities in relevant areas. It will also brighten the future bilateral collaboration between both countries.”

The four projects funded are:

1.       Low Carbon Transitions of Fleet Operations in Metropolitan Sites
(Newcastle University, Imperial College London, and Southeast University)

2.       City-Wide Analysis to Propel Cities towards Resource Efficiency and Better Wellbeing (University of Southampton and Xi’an University of Architecture & Technology)

3.       The ‘Total Performance’ of Low Carbon Buildings in China and the UK (University College London and Tsinghua University)

4.       Low carbon climate-responsive Heating and Cooling of Cities (University of Cambridge, University of Reading and Chongqing University)

The Cambridge project, led by Professor Alan Short of the Department of Architecture and also involves Professor Peter Guthrie from the Department of Engineering, will focus on how to deliver economic and energy-efficient heating and cooling to cities of different population densities and climates.

Low Carbon Cities forms part of the Low Carbon Innovation programme, a £20 million three-year investment announced in March 2014. Facilitated by Research Councils UK (RCUK) China, this programme builds on five years of successful collaborative research funded jointly by EPSRC and NSFC in energy research. Low CarbonInnovation will also support research to develop new low carbon manufacturing processes and technologies, as well as offshore renewables.

Adapted from an EPSRC press release

Researchers from UK and Chinese universities, including the University of Cambridge, are collaborating on four new projects to work towards achieving low carbon cities in the UK and China. The projects were announced as Chinese President, Xi Jinping visited the UK this week. 

Skyline - Hong Kong, China

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A democratic cacophony

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In a remote village in a forgotten corner of West Bengal lives an old man called Fakhruddin Gazi. He has lived in the village for every one of his long years. However, since India was partitioned in 1947, Fakhruddin Gazi has lived in fear, unable to leave the small landholding his family has owned for generations.

A thousand miles away in Rajasthan, the state’s first female Chief Minister is showered with garlands and the kind of affection usually reserved for pop stars, not politicians. The masses clamour to touch her feet. Devotees deify her with all the reverence of a Hindu goddess.

Just down the road in Jaipur, an enterprising and popular middle-aged man is making and receiving calls on one of his three mobile phones. The conversations he conducts link voters to politicians, slum-dwellers to local officials. If you need a fake birth certificate, a government job, or your home connected to the electrical grid – his is the number you need to call.

In Gujarat, a casually employed labourer is being interviewed. The man is a Dalit, a member of the lowest caste in India’s order of social stratification. Dalits used to go by another name – ‘untouchables’. He tells Dr Manali Desai, who has travelled from Cambridge to interview him, about his political leanings.

“Since the BJP came there have been no more riots. We live peacefully. It is not as it used to be. There is progress everywhere. It has become America now... nice cinemas and long roads have been built. It all seems like a dream.”

This is India on any given day. A cacophony of more than a billion voices and stories all straining to make themselves heard. Some shout, some whisper, others scream. Few are silent. Each and every voice – Brahmin or Dalit, Muslim or Hindu, old or young – has something unique to tell us about the nature of democracy in India: its flaws and foibles, its puzzles and paradoxes, its successes and its shames. All have their part to play in informing our understanding of the world’s largest democracy; a democracy often celebrated, regularly condemned and impossible to ignore.

Some of the stories Cambridge academics are uncovering – like Professor Joya Chatterji’s experiences with Fakhruddin Gazi – interrogate the foundations and principles of post-partition democracy, highlighting a legacy of injustice and inequality against a sub-class of India’s own citizens. The work of others, like social anthropologist Dr Anastasia Piliavsky, directly challenges the Western world’s accepted notions of what democracy should look like, arguing that our rush to brand Indian politics as a basket case of corruption and crime is, in part, a failure in our own understanding as to the needs and sensibilities of more than 800 million registered voters in India.

Chatterji’s work on refugees, minorities and the rights of marginalised groups in West Bengal and beyond raises questions about the history and meaning of citizenship for minority communities in India, particularly for individuals like Fakhruddin – an Indian Muslim caught on the ‘wrong side’ at the time of partition.

Once the head of a Sunni family that owned several acres of good paddy land and many heads of cattle, Fakhruddin has lived with the consequences of partition since the late 1940s. In the upheaval that came with the new international border and the Radcliffe Line, his family fled to East Pakistan (now Bangladesh) while he stayed to tend to the graves of his ancestors.

Gangs grabbed most of his property and burned his home while the police did nothing. In 1965, India enacted ‘enemy property’ ordinances that gave the state unfettered powers – which could not be challenged in any court – to seize the property of anyone ‘fraternising with the enemy’. Since then, Fakhruddin has been afraid to leave the tiny plot he still has, for fear of being dispossessed.

“My work looks at the origins and precise nature of minority citizenship,” says Chatterji, Director of the Centre of South Asian Studies. “Unless you understand its legacies of impoverishment, deprivation and seizure of property, addressing contemporary problems of minorities in India’s democracy will be less straightforward.

“Minority citizens are seen as ‘lesser’ and this is enshrined in the constitution. Even when India and Pakistan accorded these citizens formal membership, they set them apart legally from full citizenship in vital ways. Their standing is diminished.”

Chatterji has made extensive use of records kept in the National Archives of India, and many regional archives across the subcontinent, to supplement extensive fieldwork and oral history. Despite the current status quo and unwillingness of governments to tackle the issues surrounding minority citizenship, Chatterji does have hope for the future.

“There is much that is great about Indian democracy and much that is not. My work on internally displaced Muslims has persuaded me that the impact of partition on minorities who stayed behind was far less benign than has often been assumed. However, I do see lots of light in popular organisation and mobilisation around a host of issues of injustice in India. We don’t see this emanating from the state or high politics, but the country is absolutely teeming with everyday movements on the ground. The state has to pay attention to them. There are protests all the time; we have an Arab Spring of sorts in India every day.”

Sociologist Dr Manali Desai is another researcher with an ambivalent view on India’s future. Her recent work has looked into the reshaping of the country’s political landscape and how the ruling BJP party (historically seen as conservative and elitist) has won the significant backing of many lower-caste voters in states like Gujarat.

While the rise, and aspirational voting habits, of the Indian middle class has been much discussed and documented, Desai believes that the BJP’s paradoxical success in attracting voters from the Dalit and Other Backward Classes (OBCs) – when the personal benefits of voting BJP cannot be demonstrated – has a great deal more to tell us about 21st-century India.

“The BJP claims that the people of Gujarat support [Prime Minister] Narendra Modi because of the development he has brought to the state,” says Desai. “Yet numerous studies show that social development in Gujarat lags behind that of many states and the benefits of development have not reached beyond the middle classes.”

Desai believes that it is precisely the BJP’s ‘development discourse’ that has attracted lower-caste votes in high numbers despite many Dalits and OBCs continuing to face widespread discrimination, lacking access to water and electricity supplies, and being subject to evictions and relocations. ‘Development’ and ‘peace’ were words often uttered in interviews, something the BJP juxtaposed with an ‘unruly and chaotic’ past.

“India is still in the early stages of exploding capitalism, and for hundreds of millions of India’s young, this is all they have ever known,” says Desai. “Urban voters are not aware of rural issues and young rural men seek to migrate to cities to find jobs. This has all helped the BJP’s remarkable rise as India has repositioned itself in the global economy.”

Looking to the future, Desai says: “I am both hopeful and not. The established order of things was stultifying the economy and politics, and new technology and innovation, an increasingly young population and a new awareness of India’s place globally are all very positive developments.

“But there has also been a deepening and normalising of Hinduistic strains. This is particularly potent when young people should be opening up, not closing down. That worries me. India has very deep inequalities around caste. When not addressed, they come back with a vengeance. But overall, yes, India will become a more democratic place. Lower-caste parties rule in several states despite being excluded in more and more ways. More quotas and more jobs for lower castes is the only way around this.”

India’s democracy is a subject of consuming fascination to Anastasia Piliavsky, who in 2013 went on the campaign trail with Rajasthan’s future Chief Minister Vasundhara Raje. She was given privileged access to Raje’s campaign machine and the chance to understand what Piliavsky calls “the logic of Indian democracy” – an oxymoron to many.

Politics and corruption in the world’s largest democracy are never far from the headlines, either in Indian newspapers or on news websites around the world. A Google search for ‘Indian corruption’ returns almost as many hits as ‘Indian democracy’.

Piliavsky’s research occupies the liminal area between the two as she seeks to understand why a political system so often regarded as corrupt and amoral continually engages hundreds of millions of voters – and attracts turnouts which are the envy of many Western democracies.

Piliavsky believes that looking at India solely through the prism of Western sensibilities misses the moral significance of ‘relationships’ and ‘community’ that underpins all Indian politics – subjects that Desai also came across regularly in her interviews with Dalits and OBCs.

“In India, politics is about relations and hierarchies,” says Piliavsky. “It is about obligations and loyalties to one’s own. We may call this irruption into the bureaucratic process and law ‘corruption’. Yet it is precisely this ‘corruption’ – the sprawling, tangled web of human relations – that animates India’s democratic process and drives hundreds of millions to the voting booths.”

She contends that attachments to people, rather than ‘left’ or ‘right’, is what draws many into political life and shapes political loyalties. Voters expect politicians to give, be it food, money or public goods, as part of their responsibility to the voters. Many do not see the distribution of food and alcohol as corruption. To them, the betrayal of relations is the real meaning of corruption; when people don’t deliver to those whom they owe.

Getting anything done in India – 
from buying a car, arranging a marriage or attracting voters – requires ‘approaches’. Cash does pass hands, but there are few quick and easy sales. Each arrangement works through bonds of mutual sympathy, favour and trust. Few in politics can 
avoid spending large sums of money 
on their constituencies.

As well as defending a democracy often compared with the scandalised governments of Sub-Saharan Africa, Piliavsky is also more sanguine than many Western commentators about Modi’s Prime Ministership.

“Most of those who voted for Modi did so because they believe him to be a highly effective leader, a man who can get things done. However sound that belief may be, delivering on his many (often improbable) promises is what will keep him in office – not backing a violent ideology rejected by many Indian citizens and the international community alike. Having promised millions of new jobs and having brought many Muslims to the BJP, Modi can now ill afford communal riots.

What India has shown is that no politician is ever good enough. No one can sit pretty, Modi least of all. He’s going to have to work day and night to deliver a small portion of what he’s promised. The Indian citizens are not fools, they know he promised too much, and they will watch him closely. There is no cult of personality, only a ‘cult of action’. And if Modi’s electorate does not feel he has done enough by the end of his first term in office, they will expunge him, just as they did with Indira Gandhi before. This is the way of India’s restive, fickle democracy.”

Inset images: Election campaign in the 2014 General Election in India (Michael Bumann); A woman shows her inked thumb as proof of voting (Nilanjan Chowdhury/Al Jazeera).

India is home to one of the most vibrant, engaged and mystifying democracies on the planet. Cambridge academics, across a wide range of disciplines, are working on the ground – with citizens, charities, NGOs, fellow scholars and politicians – to try to untangle it.

The country is absolutely teeming with everyday movements on the ground. The state has to pay attention to them. There are protests all the time; we have an Arab Spring of sorts in India every day
Joya Chatterji
Queuing to vote in India
Nehru and Today's India

To complement the work of Cambridge researchers studying Indian democracy, the University is also active as a neutral and respected convener of debates in India among Indian politicians, writers, artists, economists and diplomats.

Following the success of the inaugural India-Cambridge summit in 2012, the Vice-Chancellor's Endowment Fund supported a major conference in Delhi in February 2015 on 'Nehru and Today's India', which was broadcast on NDTV, one of India's leading news channels.

Both events were conceptualised by Dr Shruti Kapila (Faculty of History), who also provided Indian election analysis for Al Jazeera and Bloomberg TV, and has inaugurated a seminar series on Indian issues in the House of Lords.

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Your Questions Answered on open access

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Open access means making peer reviewed works freely available in digital form, so that anyone with internet access can use them, without financial, legal or technical barriers. It allows users to download, copy, print and distribute works, without the need to ask for permission or to pay.

To the mark the eighth annual Open Access Week, we asked what readers wanted to know about the initiative.


Why do we need open access? How can I use it? Is it better for the sciences or the humanities?

Lucy Montgomery: Open access is a powerful mechanism for widening access to knowledge and for increasing the impact of research beyond universities. Because it makes peer-reviewed scholarship free at the point of use, open access helps ensure people who need knowledge can access it, even if they can’t afford to pay for it.

Patients scouring the internet for the latest information about rare medical conditions, scholars in the developing world, and practitioners who want to apply evidence-based research to challenges they face every day, are just a few examples of groups who benefit from open access.

The global shift to open access is being driven by a consensus that the public has a right to access publicly funded research outputs. Closed publishing models rely on recovering the costs of publishing research by selling access to it. This made sense in a print-dominated world, when the marginal costs associated with making and distributing physical copies of books and journals was high; it makes much less sense in digital landscapes where the costs of making additional copies of a work once it’s been published are very low.

 

The global shift to open access is being driven by a consensus that the public has a right to access publicly funded research outputs.Gideon Burton/Flickr, CC BY-SA

 

Once a work has been made open access, it’s free for anyone in the world to read or download. This is a boon for anyone who has ever been frustrated by a pay wall, for teachers looking for resources that can be shared easily with students, and for scholars who hope their work will contribute to a wider body of knowledge.

Although open access has been faster to take off in the sciences, it also has important benefits for scholars working in the humanities: helping authors to share their work with the communities that they write both for and about, and making knowledge and ideas available to new audiences.


How can journals meet the costs of editing, typesetting, proofreading, website construction and management if they move from subscriptions to open access?

Keyan Tomaselli: One of the key blind spots in open access discussions is the cost it poses to publishers. Journals that are not funded by foundations or universities are financially vulnerable in an open access environment unless they start charging for publishing articles. This is because their “permissions income stream”, which are paid to journals through national copyright agencies when their articles are reproduced in student course packs, will dry up.

In this model, the burden of payment will shift from reader or library payment for downloads or subscriptions, to author or institution for articles to be published. The assumption that open access is free – after data charges are paid – is wrong because though readers can access articles for free, authors and their institutions will end up paying so journals can recoup their costs. Data charges relate to the cost of internet access and downloading.

Too often one forgets that such accessing of the internet has cost implications too. And then there are journal post-production costs, including online platform hosting, marketing, discoverability, and archiving, among other things.


Open scholarship includes open notebook, open data and open review as well as open access. What are more systematic and rigorous treatments of open scholarship?

 

It’s now possible to put a digital ‘stamp’ on different scholarly outputs.Gideon Burton/Flickr, CC BY-SA

 

Danny Kingsley: There’s an increasing amount of research and discussion about open scholarship about integrity and researcher support; research management; assumptions and challenges; and about how we capture what’s being produced in repositories.

But although the nature of research is changing profoundly, the current system still only rewards and recognises traditional publication. Opening up scholarship has multiple benefits: research claims can be verified, work doesn’t have to be repeated to recreate the data, and data can be analysed from other perspectives.

It’s now possible to put a digital “stamp” on different scholarly outputs, called digital object identifiers (or DOIs). This means a researcher can be cited when another uses their work, and receive recognition.

By having an “open process” in research, we can put digital stamps on all aspects of research, such as progress in thinking through an online discussion paper, for instance; new techniques; and approaches and experiments. These can themselves be cited and therefore rewarded, rather than only recognising traditional published outputs.


How do we ensure research published under open access continues to have a system of rigorous quality checks, such as peer review, that can cope with the enormous load of research looking for publication?

James Bradley: We can’t ensure rigorous peer review of research will be undertaken under open access. Not only that, we know for sure that the explosion of open access journals has allowed for the publication of not just bogus work, but also work that’s irrelevant or useless for scientific or the whole academic enterprise.

How do we know this? For starters, there was an infamous sting in late 2013 that revealed a nonsensical piece of research was accepted for publication by a large number of open access journals. Then, there’s the research showing the huge numbers of “predatory” journals, which are basically in it for the money. The academic or the academic’s institution pays for publication and the piece gets in, regardless of quality. That’s why so many researchers often get emails from start-up journals soliciting our work — for a fee. It’s all about profit.

 

There’s another form of quality control that transcends peer review and lies in the after-life of a publication.Gideon Burton/Flickr, CC BY-SA

 

To mitigate this situation, there’s the Directory of Open Access Journals, which is supposed to act as quality control. If you make it on to the list, then you are supposed to be reputable. But some of the journals that have made it to the list are, in fact, “predatory”.

But it’s false to assume that all research that makes it into a front-rank publication is great or that all work in pay-for-publication journals is junk. The peer review system has always had flaws. Ultimately, there’s another form of quality control that transcends peer review and lies in the after-life of a publication — the opinion of your peers.

And this can, to some extent, be measured by metrics through citation databases. But it’s also reflected in the status and reputation accorded by your peers. It was ever thus, and most definitely remains the best form of quality control.


To what extent does this issue go beyond the machinations of open access versus the nuances of what’s free and not free, to the problem of the role of the university in a world where capitalism and the internet frame much of what we do?

Tom Cochrane: Open access has three points of origin. These, in no particular order, are the interests of the researcher in greater exposure and readership; the distorted economics of the price of scholarly communication (as distinct from the true cost of academic publishing); and the fact that the internet has made open access possible in the first place.

 

Openness in access to research outputs, research data and research processes, enhances replication capability, and allows review.Gideon Burton/Flickr, CC BY-SA

 

As the debate about open access has matured, it has also become clear that greater openness can also provide protection against research fraud or dishonesty. Openness in access to research outputs, research data and research processes, enhances replication capability, and allows review.

Open access has no particular correlation or causal relationship with the broader role of universities, other than to improve the efficiency and integrity of research and to increase the likelihood of greater integration with their various communities. It’s certainly true that we wouldn’t have seen it develop without the internet and, as such, the movement is another case of innovation and disruption of legacy models.


Where are we getting with the movement, year to year? How much concrete progress has there been as opposed to awareness raising?

Virginia Babour: There’s no doubt that the open access has come a long way. There are now mandates for open access in many countries and institutions globally.

These mandates vary in what they require. Some, like the one in the United Kingdom, are primarily supported through publication in open access journals. Others, like Australia’s funding councils' mandates, are via deposition of an author’s research in university repositories.

There’s also been an explosion of different technologies around open access, including new ideas on what can be published - just parts of articles, such as figures, fir instance – and new models for publishing open access books.

Finally, the infrastructure to support open access is developing with licenses for publishing, which lay out clearly how articles can be used. And identifiers for people and documents (even parts of documents), so there can be better linking of scholarly literature.

Open access is an evolving ecosystem. There will be different models to fit different specialities and probably different countries. But that’s fine if it works.

Virginia Barbour, Executive Officer, Australasian Open Access Support Group, Australian National University; Danny Kingsley, Executive Officer for the Australian Open Access Support Group, University of Cambridge; James Bradley, Lecturer in History of Medicine/Life Science, University of Melbourne; Keyan Tomaselli, Distinguished Professor, University of Johannesburg; Lucy Montgomery, Director, Centre for Culture and Technology, Curtin University, and Tom Cochrane, Adjunct Professor Faculty of Law, Queensland University of Technology

This article was originally published on The Conversation. Read the original article.

Virginia Barbour, Executive Officer, Australasian Open Access Support Group, Australian National University; Danny Kingsley, Executive Officer for the Australian Open Access Support Group, University of Cambridge; James Bradley, Lecturer in History of Medicine/Life Science, University of Melbourne; Keyan Tomaselli, Distinguished Professor, University of Johannesburg; Lucy Montgomery, Director, Centre for Culture and Technology, Curtin University, and Tom Cochrane, Adjunct Professor Faculty of Law, Queensland University of Technology answer questions about open access.

Open access

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Yes

Flashmobs and flamenco: how Spain’s greatest artform became a tool for political protest

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Flamenco is perhaps Spain’s most alluring cultural phenomenon, characterised by the stereotypes of sun, passion and tumbling black hair. Political protest and social activism are less likely to come to mind when thinking of flamenco, but for some performers it has always been a powerful tool for voicing political protest.

Never more so than today. Spain has suffered immensely in the global economic crisis – especially Andalusia, the southernmost region of the country most associated with flamenco. Neoliberalism has taken its toll on the Spanish people, who are suffering one of the highest levels of unemployment in Europe. In 2011, this led to the infamous 15M (indignados) protest movement that mobilised millions of citizens across the country to challenge policies of austerity following the banking crisis.

On the back of this movement, the flashmob group Flo6x8 has rebranded flamenco as a powerful political weapon. This anti-capitalist group has been well publicised for its political performances that have taken place in banks and even the Andalusian parliament. Using the body and voice as political tools, the group carries out carefully choreographed acciones (actions) in front of bemused bank staff and customers. These performances are recorded and then posted online, attracting a huge number of views.

 

 

Through explicitly political lyrics, Flo6x8 denounces the banking crisis and the austerity measures resulting from European bailouts. By claiming public, capitalist spaces the performers give a powerful political message that challenges the status quo. But these performances also break with typical gendered stereotypes in flamenco. The exotic, seductive and “oriental” image of the female dancer is turned on its head. Instead the female dancers in these performances become powerful, political figures.

The group believes it is repoliticising flamenco, returning to its historical origins. Nowadays flamenco is closely associated with the world music industry and tourism. Yet the origins of flamenco tell a different story. Flamenco was born among socially marginalised communities such as Gypsies, miners and other disadvantaged Andalusian groups. Lyrics from the 18th and 19th centuries tell tales of poverty and social hardship.

True, the flamenco we know today owes much of its legacy to the commercial theatres (cafés cantantes) of mid-19th century Spain. But its political side has come out during times of social upheaval. Republicans during the Spanish Civil War sang ideological messages. And singers of the 1960/70s such as Manuel Gerena and José Menese challenged the Franco regime in pursuit of democracy and equality.

 

Fandangos republicanos sung by Manuel González “El Guerrita”.

 

I want to say with passion, this fandango that I sing, Spain is Republican. And this is from the heart, down with the law and tyranny.

Flo6x8 see themselves as the continuation of this political legacy, where flamenco becomes a catalyst for social change as can be seen by this anti-austerity flashmob in the Andalusian parliament in June 2014.

 

Flo6x8 anti-austerity protest at the plenary session of the Andalusian parliament in June 2014.

 

The controversial new gag law introduced by the Spanish government in 2015 has restricted the activities of Flo6x8. Yet members remain committed to flamenco as a political weapon against continued social and economic inequalities in Spain.

Confronting racism

The history of flamenco has also been used to promote tolerance. Flamenco is said to have links to Spain’s Islamic past a period when Christians, Jews and Muslims allegedly coexisted in peace (convivencia). Although criticised by some as a utopian myth, convivencia carries a message of tolerance for today. Many argue that flamenco emerged from an amalgamation of cultural influences in southern Spain: Arabs, Jews, Gypsies, African slaves, Andalusian underclasses and so on. The belief, then, is that flamenco is born of intercultural dialogue.

However, Spain’s relationship with its Islamic past is problematic. In some quarters it is celebrated – in others it is shunned. Since the 1980s, increasing immigration into Spain, particularly from Morocco, has complicated matters. Like in many countries across Europe, racial tensions and Islamophobia have increased. Here flamenco has been used to confront racial tensions and promote tolerance.

In 2003, the dancer Ángeles Gabaldón and her company premiered the show Inmigración (Immigration), which was also broadcast online to more than 50,000 people. Inmigración raised awareness of the humanitarian issues surrounding migration across the Strait of Gibraltar: human trafficking, migrant deaths, immigrant sex work and racism.

The show, which featured a multiracial cast, sought to raise awareness of the social reality of immigration – and, interestingly, also presented Spain’s own history of emigration before it became a country of immigration. But the most powerful element of Inmigración was how the past and the present were joined together in musical performance. Flamenco was combined with musical styles believed to have originated in Islamic Spain that now exist in North Africa.

The cast included Jalal Chekara, a Moroccan performer who has lived in Spain for many years. He is known for his collaborations with flamenco musicians, promoting tolerance through the musical re-imagining of a shared cultural history.

Since 2003, the situation across Spain and Europe has deteriorated. The current migrant crisis is maybe the most difficult challenge facing Europe and Inmigración is perhaps even more relevant today than when it was first performed. It shows the capacity of flamenco as a form of social criticism that can give power to the powerless and voice to the voiceless.


Joshua Brown, a lecturer in Ethnomusicology at Chapman University and Juan Pinilla, flamenco singer and writer in Granada, assisted with research for this article. The author will be appearing at the Cambridge Festival of Ideas.

Matthew Machin-Autenrieth, Leverhulme Early Career Fellow, University of Cambridge

This article was originally published on The Conversation. Read the original article.

Matthew Machin-Autenrieth (Faculty of Music) discusses flamenco and its use as a tool of social activism.

Flamenco

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Yes

Interactions with Africa are in "the University's DNA"

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Talks covering work on tackling the ebola outbreak to supporting young scholars formed part of the Cambridge-Africa Day 2015.

Speaking at the opening of the event, Professor Sir LeszekBorysiewicz highlighted the importance to the University of its unique research capacity-building initiative.

“The speed with which the Cambridge-Africa Programme has developed is phenomenal. We are trusted by our partners, and the programme has buy-in from our academic community. This has been essential to the programme’s success. Today, it is no longer something done by a handful of enthusiasts. It is now something embedded in the University’s DNA,” said the Vice-Chancellor.

His remarks echoed the words of Professor David Dunne, founder and director of the Cambridge-Africa Programme, who had earlier expressed his aspiration that, in the future, “partnership with, and support for, African research institutions will be a core part of the University’s work.”

Setting the scene for a day of presentations by researchers involved in collaborative projects, Prof Dunne identified one of the challenges facing research institutions across the African continent: “There is an insufficiency of internationally competitive researchers to mentor and train the young talent, and to accelerate Africa’s success.”

“The Cambridge-Africa Programme aims to tackle that mentorship gap, while avoiding the dependency and loss of indigenous talent that so often occurs when better opportunities are available outside of Africa to African researchers.”

The morning session included presentations by researchers from Cambridge and from African partner institutions involved in the Cambridge-Africa Programme. Subjects ranged from the transmission of disease between fruit bats and humans in Ghana, to the promotion of sustainable agricultural practices in southern Tanzania, to the link between conservation and tourism in Uganda’s national parks.

The afternoon’s keynote speaker, Dr Monique Nsanzabaganwa, Vice Governor of the National Bank of Rwanda, described some of the recent developments in governance, health and education:

“There are some very good things happening in Sub-Saharan Africa –and in Rwanda in particular. Those stories must be told by voices that have credibility and knowledge. We would like Cambridge to be our partner in capturing and analysing these changes even as they happen.”

Afternoon sessions focused on ways in which Cambridge and African scientists support each other to produce excellent science. Dr Dan Masigo, of Uganda’s International Centre of Insect Physiology and Ecology, described the collaboration within the THRiVE (Training Health Researchers into Vocational Excellence) initiative.

Professor Allison Elliott, of the Uganda Virus Research Institute (UVRI), discussed the work carried out by the MUII partnership, which involves Cambridge, UVRI, Makerere University, and the London School of Hygiene and Tropical Medicine. Irene Tamajong, UK director of the African Institute of Mathematical Sciences-Next Einstein Initiative, reminded the audience of the strength of AIMS’ links to Cambridge, and the shared interest in research excellence.

Later, Helen Pennant, Director of the Cambridge Trust, emphasised the role of scholarships in building research capacity –with specific reference to the cohort of newly arrived Cambridge Trust scholars from Sub-Saharan Africa. In one of the day’s final presentations, Professor Ian Goodfellow shared his experiences of working in Sierra Leone at the height of the most recent Ebola epidemic.

The well-attended event at St John’s College reflected the burgeoning awareness, within the University and beyond, of the various initiatives comprising the Cambridge-Africa Programme. In its variety, the audience of students, researchers, administrators, funders and partner organisations embodied the African saying quoted by the Vice-Chancellor in his opening address: “If you want to travel fast, then travel alone. If you want to go far, then travel together.”

 

Vice-Chancellor hails success story as programme celebrates second Cambridge-Africa Day.

The Cambridge-Africa Programme is now something embedded in the University’s DNA.
Vice-Chancellor Prof Sir Leszek Borysiewicz
DNA on an agarose gel

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Yes

A glimpse of India

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For most people, owning a mobile phone also means owning a video camera. There is no cost at all in sharing with others the scenes you film, thanks to YouTube and other such sites, so you can film nearly everything you do. In 1935, this was not the case. A cine film camera was expensive, film was not cheap and developing it was particularly pricey. You could not waste hours of expensive film waiting for your cat to do something funny, your baby to belch hilariously or some stranger’s dog to chase deer across a national park. People filming home movies had, therefore, to be more selective about what they filmed. There is as much difference between one of these films and most YouTube clips as there is between a letter written in 1935 and the majority of the emails you have sent recently.

As the archivist of the Centre of South Asian Studies’ Collection, I am effectively responsible for a set of home movies which, when analysed, bears great resemblance to the sort of documents historians, anthropologists and others working in the arts, humanities and social sciences have relied on for many years. Some, like newspapers, document significant events. In our own collections, for example, we have film of the funeral of Lord Brabourne (Gradwell 1), footage of the aftermath of the Quetta earthquake of 1935 (Berridge 4), a train derailed by pro-independence activists in c.1938 (Berridge 5) and two very harrowing films of the catastrophic results of the mass migrations that followed Partition in 1947 (Williams 1 and 2) as well as footage of refugees arriving in Lahore in the same period (Burtt 3 and 7). Others, a bit like official documents, show the working of the Empire, the ways in which the infrastructure of the Raj was built, such as the building of the railways (Berridge 1), or the vast canal systems of the North-West (Stokes 12 and 13).

Some of the films are similar in tone to the letters in our paper archive – made to be sent home so that people could show those back in the UK what their new life was like, such as the first few films of the Hunter Collection, which are actually filmed to look like a letter inviting viewers on a holiday to India and showing them what they will see when they arrive. And some show, often accidentally, the lives of Indian people (Banks 5), as well as the lives of the British who ran the Imperial system – the garden parties (Meiklejohn 8), hunting/horse-riding (Banks 2) social gatherings and sports, and also more personal, domestic scenes in which we are shown the homes and gardens of British India (Stokes 3).

The Collection is perhaps most interesting, though, when the films reveal something unintended by the film-maker, enabling an insight into the situation in which the film was made or into the mindset of the person holding the camera. The writer of a letter, diary or government document is able to exercise absolute control of the narrative that is presented, but this is not always the case in a film, as those being filmed can act in ways that tell us more about the context in which the document was created.

Two examples jump out at me – one is a flippant example of what films can reveal, the other asks some interesting and important questions about social attitudes and about what a British woman is willing to have her audience see when viewing the films she made, or about what is acceptable in certain social settings.  I shall leave these deeper questions without an answer, though – my role as an archivist is to prepare, preserve and present our collections, not to interpret them. There is, however, a growing branch of academic study which is using film collections such as ours as tools for visual anthropological study: the work of my colleague Dr Annamaria Motrescu-Mayes would be an excellent starting point for those who wish to read further on this subject, and a good deal of it is based on the films mentioned in this article.

The two films come from the Kendall Collection and both are, somewhat unusually, made by a woman, Lady Kendall, who was the wife of a judge in Allahabad. Kendall 1 shows mainly domestic scenes: the garden being tended, a children’s party, people walking in the family garden. Towards the end there is footage of a wedding. These scenes are interspersed with footage of Indian agricultural workers operating an irrigation system. This juxtaposition is, in itself, interesting.

While it shows the lifestyle of an affluent member of British Indian society, however, it also reveals something quite simple. It is clear that this was the first film taken on a new camera. You can tell this not because of the quality of the footage, but because of the way the camera was used – the film-maker treats it like a still camera. She points it at an object or scene, captures the image and then turns it off. What this leaves is a dizzying collection of short clips, mostly lasting between one and two seconds. Even when longer scenes are filmed – the wedding at the end or the agricultural scenes, for example – these are taken in short episodes. In the whole 10 minutes of the film, there are very few times when the camera is turned on for longer than four or five seconds. It is very difficult to watch, and even harder to watch to the end without getting a headache.

It is entirely understandable, however. We are used to watching what we have filmed straight away, and if we are doing something wrong, we can correct it with our next recording. Lady Kendall had to wait until the film she was using was completely recorded and then take it to be developed. Given that she shot 10 minutes of film in sections of a few seconds at a time, it is likely that it took quite a while to fill the whole reel. After viewing it she corrects her use of the camera – if you watch the whole Collection, you will see that the shots in subsequent films gradually lengthen.

Kendall III is more complex, although it also has at its heart the problems associated with making the switch from taking photographs to shooting films. In this film, Lady Kendall shows a picnic in the hills. After showing a group of friends (and a larger group of bearers and other servants) making their way up to the picnic site, she tries to take what is essentially a photograph of the scene, composing it to suit what she wants the image to show. She does this, though, with the cine camera running.

This provides us with a very revealing moment – it starts 42 seconds into the film (just after footage of a tennis match and some shots of mountains), and only lasts a second. Standing behind the people, seated on their blankets and smiling and laughing through their sandwiches, is a servant in livery.

For some reason, Lady Kendall, who has been quite happy to show the servants involved in carrying the picnic things up the mountain, does not wish to have this servant in this shot, so she asks one of the party to stand and obscure him from the camera’s view. The servant initially sways slightly to his right to try and stay in the shot, but then steps across to his left, remaining firmly visible. The friend moves back across to block him again, clearly taking direction of where she should stand, at which point Lady Kendall stops filming.

This attempt to create a mise-en-scène clearly fails, but in doing so it opens up many questions and lines of enquiry. Why the servant wants to remain in the shot, where he is clearly not wanted, for example. It also suggests that there are some situations in which it is acceptable for servants to be shown in the film, and others where it is not. Why this might be is not immediately clear, but this does show that a film can helpfully shed light on social attitudes, conventions and mores in a way that a written account would not. A diary entry or letter about this picnic would have simply not mentioned the presence of the servant, obscuring him far more effectively than Lady Kendall’s friend is able to do in this short piece of footage.

Inset images: stills from the Kendall III film (Centre of South Asian Studies Archive).

This article was first published in CAM Issue 75 (2015).

Kevin Greenbank, archivist at the Centre of South Asian Studies, explores the ways in which the home movie offers fascinating insights into the lives of those in front of, and behind, the camera – as rare footage of a 1935 Raj picnic shows.

The Collection is perhaps most interesting when the films reveal something unintended by the film-maker
Kevin Greenbank
Stills from the Kendall III film
The Centre of South Asian Studies Archive

The Centre of South Asian Studies’ film archive was largely collected by its remarkable first archivist, Mary Thatcher, who was commissioned in 1967 to begin a search for archival material that was otherwise in danger of being lost.

Her brief was to focus on ordinary British men and women who worked in India, either in the Civil Service or its associated governmental concerns, those who lived in the Princely States, or were in the private sector, or served as missionaries or teachers. The resulting trawl of families who had returned to Britain after Independence has resulted in an archive of international importance and renown.

The Collection deals mostly with the British in India (Indian collections would generally be restored to Indian archives, rather than being kept out of the country) and includes papers, photographs and films, and an oral history collection.

The unique collection of amateur cine films comprises films mostly made in the 1920s, 1930s and 1940s. Where the archive has a film, it also normally has accompanying papers and photographs, providing a rare level of documentation and analysis.

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Yes

Social yeast cells prefer to work with close relatives to make our beer, bread & wine

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The findings, published today in the open access journal eLife, could lead to new biotechnological production systems based on metabolic cooperation. They could also be used to inhibit cell growth by blocking the exchange of metabolites between cells. This could be a new strategy to combat fungal pathogens or tumour cells.

“The cell-cell cooperation we uncovered plays a significant role in allowing yeast to help us to produce our food, beer and wine,” says first author Kate Campbell.

 “It may also be crucial for all eukaryotic life, including animals, plants and fungi.”

Yeast metabolism has been exploited for thousands of years by mankind for brewing and baking. Yeast metabolizes sugar and secretes a wide array of small molecules during their life cycle, from alcohols and carbon dioxide to antioxidants and amino acids. Although much research has shown yeast to be a robust metabolic work-horse, only more recently has it become clear that these single-cellular organisms assemble in communities, in which individual cells may play a specialised function.

For the new study funded by the Wellcome Trust and European Research Council, researchers at the University of Cambridge and the Francis Crick Institute found cells to be highly efficient at exchanging some of their essential building blocks (amino acids and nucleobases, such as the A, T, G and C constituents of DNA) in what they call metabolic cooperation. However, they do not do so with every kind of yeast cell: they share nutrients with cells descendant from the same ancestor, but not with other cells from the same species when they originate from another community.

Using a synthetic biology approach, the team led by Dr Markus Ralser at the Department of Biochemistry started with a metabolically competent yeast mother cell, genetically manipulated so that its daughters progressively loose essential metabolic genes. They used it to grow a heterogeneous population of yeast with multiple generations, in which individual cells are deficient for various nutrients.

Campbell then tested whether cells lacking a metabolic gene can survive by sharing nutrients with their family members. When living within their community setting, these cells could continue to grow and survive. This meant that cells were being kept alive by neighbouring cells, which still had their metabolic activity intact, providing them with a much needed nutrient supply. Eventually, the colony established a composition where the majority of cells did help each other out. When cells of the same species but derived from another community were introduced, social interactions did not establish and the foreign cells died from starvation.

When the successful community was compared to other yeast strains, which had no metabolic deficiencies, the researchers found no pronounced differences in how both communities grew and produced biomass. This is implies that sharing was so efficient that any disadvantage was cancelled out. 

The implications of these results may therefore be substantial for industries in which yeast are used to produce biomolecules of interest. This includes biofuels, vaccines and food supplements. The research might also help to develop therapeutic strategies against pathogenic fungi, such as the yeast Candida albicans, which form cooperative communities to overcome our immune system.

Reference

Kate Campbell, Jakob Vowinckel, Michael Muelleder, Silke Malmsheimer, Nicola Lawrence, Enrica Calvani, Leonor Miller-Fleming, Mohammad T. Alam, Stefan Christen, Markus A. Keller, and Markus Ralser

Self-establishing communities enable cooperative metabolite exchange in a eukaryote eLife 2015, http://dx.doi.org/10.7554/eLife.09943

Baker’s yeast cells living together in communities help feed each other, but leave incomers from the same species to die from starvation, according to new research from the University of Cambridge.

The cell-cell cooperation we uncovered plays a significant role in allowing yeast to help us to produce our food, beer and wine
Kate Campbell
Metabolic cooperation in a social Baker’s yeast community. Pictured is a two-day old yeast community that grows as a colony. Different colours indicate cells producing and consuming different metabolites and nutrients.

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Yes

Earthquakes without frontiers

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The Ganges is India’s most iconic river, flowing from the Himalaya to the Bay of Bengal, and its massive river basin is one of the most fertile and densely populated regions in the world. The Ganges flows through 29 cities with a population over 100,000, 23 cities with a population between 50,000 and 100,000, and close to 50 towns.

But someday – perhaps tomorrow or perhaps in 100 years – a massive earthquake will hit the region, and the consequences could be catastrophic: as many as a million lives in the Ganges river basin could be at risk, primarily because buildings have not been constructed to be earthquake resilient, despite the fact that the relevant building codes are in place.

Of course, earthquakes don’t respect borders, and India is not alone in being at risk due to poorly constructed buildings. Northern India lies in the Alpine–Himalayan earthquake belt, which stretches from the Mediterranean to the Pacific. It is the second-most seismically active region in the world, and responsible for around 20% of the world’s largest earthquakes. The belt is being created by ongoing plate tectonics: as the African, Arabian and Indian plates continue to move northwards, they collide with the Eurasian plate.

The earthquake belt includes the most famous of the great trade routes, the Silk Road, which follows the edges of deserts and mountains, and high plateaus like Tibet. The landscape of the Silk Road has been shaped by earthquakes over millions of years: forcing mountains upwards and making life in the desert possible by controlling where water comes to the surface.

As the earthquake faults grind rocks together they make an impermeable clay, which often forces water to the surface along spring lines, determining where people live. To the casual observer, it seems as if the major earthquakes in this part of the world often seem to ‘target’ towns and cities but, in reality, people are often simply living where the water is, which is also where earthquakes happen.

Between 2 and 2.5 million people have died in earthquakes since 1900. Approximately two thirds of those deaths occurred in earthquakes in the continental interiors – places like northern India. Over that time, advances in the scientific understanding of earthquakes have been translated into impressive resilience in places where the hazard is well understood, which are mainly on the edges of the oceans. Comparable advances have not, however, taken place in most parts of the continental interiors, where the hazard is still much less well identified and poorly understood.

“Earthquake science has progressed so that we’re now much better at recognising the signals in the landscape that tell us whether a particular place is dangerous,” says Professor James Jackson, Head of Cambridge’s Department of Earth Sciences. “We can’t tell you exactly when an earthquake is going to happen, but we can say it will happen, not least because it’s happened before. If it’s happened before, it will happen again. What we can do, however, is to understand earthquakes better and use that knowledge to help make buildings safer.”

Four years ago, with funding from the Natural Environment Research Council, Jackson and colleagues from other universities in the UK established Earthquakes Without Frontiers (EWF), an international partnership bringing together earthquake scientists from across the great earthquake belt, from China to Italy, in order to share expertise. “But it soon became clear that the project was about much more than earthquake science, and the real issue was how to translate science into effective policy, which requires an understanding of the social context in which people live,” says Jackson.

With additional funding from the Economic and Social Research Council, EWF expanded to include social science and policy dimensions. The project, which runs until 2017, has three overarching objectives: to increase knowledge of earthquake hazards across the region; to establish greater resiliency against these hazards; and to establish a well-networked interdisciplinary partnership to support local earthquake scientists. Within Asia, there are more than 50 national level stakeholders who are working with EWF on earthquake risk reduction.

Across much of the earthquake belt, people live in large cities, mostly in poorly built apartment blocks and buildings that have not been designed to withstand earthquakes. Large cities such as Tehran, Almaty and Bishkek have all been destroyed multiple times by earthquakes, and it’s only a matter of time before the next one hits. The problem that EWF faces is convincing the public and policy makers of the importance of making towns and cities more earthquake resilient.

“In these big cities, everyday life is difficult enough: they’re very congested, they have huge problems with traffic, air quality, water quality, food supply and poverty,” explains Jackson. “And quite understandably, the risk of an earthquake seems quite remote compared to daily worries. But that doesn’t make the threat go away.”

“We face two main problems: the first is that there is a lack of awareness of the fact that seismologists cannot predict earthquakes – it’s just not something we are able to do or will be able to do,” says Dr Supriyo Mitra of the Indian Institute of Science Education and Research Kolkata. Mitra obtained his PhD at Cambridge, and is now one of the key Indian academic collaborators on the project, primarily working in Indian-administered Kashmir. “The other problem is that there is a lot of resistance to making buildings safe. It is an additional cost, but it’s a necessity and we need to get that across to people.”

Perhaps the most important change that can be made to increase earthquake resilience in these areas is the enforcement of building codes. The building codes in Los Angeles and Tehran are similar, but the difference is that in Los Angeles, most buildings are constructed according to those codes, while in Tehran most are not, so as a result, Los Angeles is highly resilient to earthquakes, while Tehran remains very vulnerable.

“Enforcement comes not just from legal enforcement, but education,” adds Jackson. “People are really starting to realise that this is important. And once you educate the public, it rises up the agenda because the public insists that it does.

“There are going to be around a billion new homes built across Asia over the next 10 years – let’s build them so they are safe.”

The Alpine–Himalayan belt, which stretches from the Mediterranean to the Pacific, is one of the world’s most seismically active regions. Now, a combination of earth science, social science and education is being used to help the region become more resilient to earthquakes, protecting lives and property.

We can’t tell you exactly when an earthquake is going to happen, but we can say it will happen, not least because it’s happened before. If it’s happened before, it will happen again.
James Jackson
The city of Muzafarabad, Pakistan lays in ruins after the 2005 Kashmir earthquake that hit the region.

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Yes

Entanglement at heart of 'two-for-one' fission in next-generation solar cells

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An international team of scientists have observed how a mysterious quantum phenomenon in organic molecules takes place in real time, which could aid in the development of highly efficient solar cells.

The researchers, led by the University of Cambridge, used ultrafast laser pulses to observe how a single particle of light, or photon, can be converted into two energetically excited particles, known as spin-triplet excitons, through a process called singlet fission. If singlet fission can be controlled, it could enable solar cells to double the amount of electrical current that can be extracted.

In conventional semiconductors such as silicon, when one photon is absorbed it leads to the formation of one free electron that can be harvested as electrical current. However certain materials undergo singlet fission instead, where the absorption of a photon leads to the formation of two spin-triplet excitons.

Working with researchers from the Netherlands, Germany and Sweden, the Cambridge team confirmed that this ‘two-for-one’ transformation involves an elusive intermediate state in which the two triplet excitons are ‘entangled’, a feature of quantum theory that causes the properties of each exciton to be intrinsically linked to that of its partner.

By shining ultrafast laser pulses – just a few quadrillionths of a second – on a sample of pentacene, an organic material which undergoes singlet fission, the researchers were able to directly observe this entangled state for the first time, and showed how molecular vibrations make it both detectable and drive its creation through quantum dynamics. The results are reported today (26 October) in the journal Nature Chemistry.

“Harnessing the process of singlet fission into new solar cell technologies could allow tremendous increases in energy conversion efficiencies in solar cells,” said Dr Alex Chin from the University’s Cavendish Laboratory, one of the study’s co-authors. “But before we can do that, we need to understand how exciton fission happens at the microscopic level. This is the basic requirement for controlling this fascinating process.”

The key challenge for observing real-time singlet fission is that the entangled spin-triplet excitons are essentially ‘dark’ to almost all optical probes, meaning they cannot be directly created or destroyed by light. In materials like pentacene, the first stage – which can be seen – is the absorption of light that creates a single, high-energy exciton, known as a spin singlet exciton. The subsequent fission of the singlet exciton into two less energetic triplet excitons gives the process its name, but the ability to see what is going on vanishes as the process take place.

To get around this, the team employed a powerful technique known as two-dimensional spectroscopy, which involves hitting the material with a co-ordinated sequence of ultrashort laser pulses and then measuring the light emitted by the excited sample. By varying the time between the pulses in the sequence, it is possible to follow in real time how energy absorbed by previous pulses is transferred and transformed into different states.

Using this approach, the team found that when the pentacene molecules were vibrated by the laser pulses, certain changes in the molecular shapes cause the triplet pair to become briefly light-absorbing, and therefore detectable by later pulses. By carefully filtering out all but these frequencies, a weak but unmistakable signal from the triplet pair state became apparent.

The authors then developed a model which showed that when the molecules are vibrating, they possess new quantum states that simultaneously have the properties of both the light-absorbing singlet exciton and the dark triplet pairs. These quantum ‘super positions’, which are the basis of Schrödinger’s famous thought experiment in which a cat is – according to quantum theory – in a state of being both alive and dead at the same time, not only make the triplet pairs visible, they also allow fission to occur directly from the moment light is absorbed.

“This work shows that optimised fission in real materials requires us to consider more than just the static arrangements and energies of molecules; their motion and quantum dynamics are just as important,” said Dr Akshay Rao, from the University’s Cavendish Laboratory. “It is a crucial step towards opening up new routes to highly efficiency solar cells.”

The research was supported by the European LaserLab Consortium, Royal Society, and the Netherlands Organization for Scientific Research. The work at Cambridge forms part of a broader initiative to harness high tech knowledge in the physical sciences to tackle global challenges such as climate change and renewable energy. This initiative is backed by the UK Engineering and Physical Sciences Research Council (EPSRC) and the Winton Programme for the Physics of Sustainability.

Reference:
Bakulin, Artem et. al. ‘Real-time observation of multiexcitonic states in ultrafast singlet fission using coherent 2D electronic spectroscopy.’ Nature Chemistry (2015). DOI: 10.1038/nchem.2371

The mechanism behind a process known as singlet fission, which could drive the development of highly efficient solar cells, has been directly observed by researchers for the first time.

Harnessing the process of singlet fission into new solar cell technologies could allow tremendous increases in energy conversion efficiencies in solar cells
Alex Chin
Pentacene molecules convert a single photon into two molecular excitations via the quantum mechanics of singlet fission

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Yes

Earthquake rocks Afghanistan and Pakistan – an area prone to magnitude 7 quakes

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A devastating earthquake struck the Hindu Kush region of north-east Afghanistan just after lunchtime on October 26, rocking communities as far away as Tajikistan, Pakistan and even India. A devastating earthquake struck the Hindu Kush region of north-east Afghanistan just after lunchtime on October 26, rocking communities as far away as Tajikistan, Pakistan and even India.

The strong quake, estimated at magnitude 7.5 by the US Geological Survey (USGS), had its origins more than 200km deep beneath Earth’s surface, and was felt as strong shaking across a very wide area. Casualties have been reported from across the region, with widespread landslips causing potential further damage to infrastructure.

So far it has been reported that 150 people have died, but this number is likely to rise.

The quake is the second large shake to hit the Alpine-Himalayan earthquake belt this year, following the one that devastated Nepal in April. A region stretching from the Mediterranean through Anatolia, Iran and Central Asia into the mountains of South-East Asia, the Alpine-Himalayan belt is the home of around a fifth of the world’s largest earthquakes.

 

Tectonic plates collide.LennyWikipedia~commonswiki, CC BY-SA

 

The earthquake was driven by collision between the Eurasian tectonic plate to the north and the Indian plate to the south. The area marks the scar of the closure of an ancient ocean, the Thethys, which once separated the continents of Gondwana, including most of the landmasses in today’s southern hemisphere, and Laurasia, made up of most of the countries that are today in the northern hemisphere.

The Hindu Kush has experienced many such earthquakes before today, and this latest appears to follow closely the pattern of those of the past. Preliminary analysis by the USGS indicates that it was caused by a deep fault in which rocks thrust past each other instantaneously. They point out that seven earthquakes of magnitude 7 or more have hit within 250km of the current earthquake over the past century. Most recently the magnitude 7.4 earthquake, some 20km west of the latest event, killed over 150 people in March 2002.

This type of deep fault, a near-vertical a thrust fault, is a process that has previously been associated with the tearing off of sections of ancient ocean floor sinking into the Earth’s mantle beneath today’s continent. Researchers have previously suggested that earthquakes in the Hindu Kush can be caused by the break off of strips of such slabs, stretching and tearing free, on geological time scales, as they fall deep into the mantle.

Whatever the geological triggers for the quake, grieving communities will now be gathering themselves together and guarding against the inevitable aftershocks. With increased understanding of the risks that Earth poses along this seismic belt, it is important to be aware and prepare for future large earthquakes. If buildings are not to be destroyed time and again, it is important to adopt and adhere to construction and planning codes. A key step in promoting legal enforcement is educating the community about the risks, as well as how to respond as safely as possible during an earthquake.

Efforts such as the “Earthquakes without Frontiers” continue to highlight the risks of earthquakes, and have drawn attention to the tectonic forces that stand poised to strike along Tethys’ former shores.

Simon Redfern, Professor in Earth Sciences, University of Cambridge

This article was originally published on The Conversation. Read the original article.

The opinions expressed in this article are those of the individual author(s) and do not represent the views of the University of Cambridge.

Professor Simon Redfern (Department of Earth Sciences) discusses the devastating earthquake that struck Afghanistan on October 26 and the geological triggers that caused it.

Topography of Hindu Kush.

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Saved from the Nazis in 1938: Schnitzler archive to remain in Cambridge

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Now, more than 75 years after it was spirited out of Austria under the noses of Nazis intent on burning and destroying Jewish cultural works, the papers of the man who inspired Freud, Kubrick and many others have been officially signed over into the care of Cambridge University Library.

Following several months of discussions with the writer’s grandsons and surviving heirs to his estate, Michael and Peter Schnitzler, the agreement concludes a handover process that began in the 1930s before being interrupted by the onset of the Second World War.

Cambridge University Librarian Anne Jarvis said: “Cambridge University Library has always been proud of the role it played in saving the Schnitzler archive from certain destruction – and we are delighted to have reached agreement with the family to ensure that this unique collection remains in Cambridge and continues to benefit from the expert care and conservation it has received over the last eight decades.

“Arthur Schnitzler’s unique legacy continues to resonate and inspire, just as it has over the last 75 years. As one of the world’s great research libraries we are committed to making this fascinating archive available to as many people as possible.”

The archive is currently being opened up to scholars and other interested readers by major edition projects in Austria, Germany and the UK. The German and UK projects will result in cutting-edge digital editions of works from 1905–1931, to be hosted, with open access, by the University Library.

Andrew Webber, Professor of Modern German and Comparative Culture at the University’s Department of German and Dutch, leads the UK editorial team, funded by the Arts and Humanities Research Council. He said: “We are delighted that this agreement has been reached. In the Schnitzler papers, Cambridge has custody of a treasure of Modernist literary culture. The edition projects are already making remarkable discoveries as the teams of scholars decipher and analyse drafts and notes recorded in Schnitzler’s idiosyncratic handwriting. They promise an exciting new view of the works and the creative processes of this key figure.”   

The story of how Schnitzler’s archive came to Cambridge is a remarkable and complex one. Upon Arthur Schnitzler’s death in 1931, his estate remained in his Vienna house with his ex-wife Olga, who was considered his widow even though the couple had divorced in 1921.

By 1933, the works of Schnitzler and other Jewish artists were regularly being consigned to the flames of the Nazis’ book burning rallies across Germany. In March 1938, Germany invaded Austria and many prominent Jews were arrested and dispossessed.

Worried that they would come for Schnitzler’s papers, Olga Schnitzler asked an acquaintance in Vienna, a student from Cambridge called Eric Blackall, if he might be able to help save them.

On March 19, 1938, at her request, Blackall sent an urgent message to Cambridge University Library to ask whether they would accept the more than 40,000 pages of Schnitzler’s literary archive. They agreed immediately, and a diplomatic seal was placed on the material before Blackall organised its shipment from Nazi-occupied Austria. More than a dozen cases and cupboards of manuscripts, sketches, notes, correspondence and even Schnitzler’s death mask made their way across Europe to Cambridge.

The communications between Blackall and Cambridge, preserved in Cambridge University Library, have the character of a spy novel, with Blackall referring to the urgent need to see that ‘mother’ (Olga) and ‘child’ (the archive) are safely dispatched to England.

Once both were safe in Cambridge, a legal document was drawn up and agreed between Olga and the Library in 1939, giving the archive to the University.  However, Olga had neglected to notify the Library that she was not Arthur’s legal heir according to his last will. When her son, Heinrich, who was the sole heir and had emigrated to the United States, asked for the archive to be returned to him, the University Librarian let him know that the papers had been given to the library by Olga and must remain there.

Olga herself left for the United States, taking some of the most personal artefacts (such as diaries and family letters) with her, with the blessing of the University Librarian at the time.

Due to the outbreak of World War II, no further negotiations took place and Heinrich Schnitzler agreed to leave the archive in the custody of the Library, provided that he be given access to the archive and that microfilm copies of the papers were made. 

Over the course of the following decades, the Library maintained a correspondence with Heinrich, who worked on his father’s papers, but the Schnitzler family remained owner of the archive. The agreement between CUL and Arthur Schnitzler’s grandsons puts to an end a legally awkward situation.

Schnitzler’s works provided the inspiration for Stanley Kubrick’s Eyes Wide Shut, David Hare’s The Blue Room as well as plays penned by Tom Stoppard. Taking love, death and human sexuality as frequent themes for exploration, Schnitzler’s works were controversial and were even denounced by Hitler as examples of ‘Jewish filth’.

The archive in Cambridge also contains Schnitzler’s only surviving letter to friend and admirer Sigmund Freud as well as his correspondence with Theodor Herzl, the founder of Zionism and other leading artists and writers of the era – such as Henrik Ibsen, Richard Strauss and Gustav Mahler.

Saved from destruction by the Nazis and smuggled in secret to Cambridge, the rescue of author Arthur Schnitzler’s archive is as dramatic as any fiction he committed to paper.

Cambridge University Library has always been proud of the role it played in saving the Schnitzler archive from certain destruction.
Anne Jarvis
Arthur Schnitzler, 1912

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Yes

V is for Venomous Snake

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Recent reports of a world shortage of anti-venom have drawn attention to the dangers of snake bite, especially in rural areas of developing countries where many people work in the fields, often without shoes to protect them.

Although several hundred of most of the world’s 3,000 or more snake species are not venomous, several hundred  species are. Among them is the Australian brown snake (Pseudonaja textilis). Judged to the world’s second most venomous land snake (the most venomous is the black mamba), it thrives in the populous eastern side of the country. The brown snake only attacks humans as a last resort but, if untreated, its bite can prove fatal.

Snakes store venom in glands in their mouths and deliver it into their victims through hollow fangs. For many years, scientists thought that snakes made venom by modifying the proteins present in their spit but not elsewhere in their bodies. This argument made sense because snake spit contains substances that enable them to break down and digest their prey.

Recent research suggests a different picture: the vast majority of the proteins and enzymes found in venoms are very similar to substances found in other parts of snakes’ bodies – such as their livers and digestive organs. The genes that control the production of these substances in snakes become activated in the salivary glands where they produce venoms.

“Weaponising is the term we use to describe the way in which snakes like the Australian brown convert a protein utilised for their own biology into a toxin – without poisoning themselves. In some cases snakes hijack their own clotting mechanisms to make venom that, once injected, causes widespread consumption of clotting factors, microthrombosis in organs and systemic bleeding,” says Professor Jim Huntington, a principal investigator at Cambridge Institute for Medical Research (CIMR).

“By understanding more about the weaponised proteins, we can learn more about an essential attribute of blood, its ability to clot when needed – in humans as well as snakes.”

The focus of Huntington’s lab is the development of a detailed understanding of the regulatory mechanisms that determine haemostatic balance – the balance between bleeding and thrombosis. It is expected that such information will inform the development of therapies for the prevention and treatment of diseases such as haemophilia, deep vein thrombosis, pulmonary embolism, heart attack and stroke – all of which are devastating conditions.

Snake venom offers a route to a better understanding of the haemostatic system. In 2013, Huntington and colleagues published research that revealed the crystal structure of the prothrombinase complex from the venom of the brown snake. This complex is quite similar to human prothrombinase which converts prothrombin to thrombin, the final step in the blood coagulation cascade. An excess production of thrombin causes thrombosis, and insufficient production of thrombin results in bleeding.

The crystal structure of brown snake venom enabled Huntington’s lab to gain new insights into the architecture and mechanism of the prothrombinase complex. Work is ongoing to determine how the snake’s prothrombinase relates to human prothrombinase and the intrinsic Xase complex (the proteins that activate coagulation factor X). Similar research from the Huntington lab has recently led to the creation of a new drug candidate for the treatment of thrombosis; ‘ichorcumab’ is currently in preclinical development as an antithrombotic agent that does not cause bleeding.

Only in the last 50 years have scientists begun to explore the potentially positive contribution of venoms to medicine. For many hundreds of years, snakes have been numbered among the most dangerous creatures on earth – to be avoided at all costs – and snake venom has long evoked fear and curiosity. Before the development of the first anti-venom at the Pasteur Institute in French Indochina in the 1890s, a bite from a venomous snake could mean death. Even today, the annual global death toll from snake bites is conservatively estimated at 20,000, and could be as high as 94,000.

PhD student James Hall (Department of History and Philosophy of Science) is looking at the serpentine narratives that unfolded during British involvement India from the later 18th century, initially under the rule of the East India Company and then under the Crown Raj from 1858.  His research explores the ways in which moral attitudes to snakes informed attempts to describe and categorise them and shaped early attempts to assess the nature and effects of venom on human and other animal bodies.

Hall’s source materials are scientific books and papers, newspapers and periodicals, travelogues, and government archives from Britain and India, as well as the literature of the colonial world. A famous example of the latter is Rudyard Kipling’s short story Rikki-Tikki-Tavi from The Jungle Book (1894). It charmingly anthropomorphises the contest between good (in the character of the valiant mongoose Rikki) and evil (the deadly cobras Nag and Nagaina), with the drama taking place in the home of a middle-class British family living in India. Rikki’s bravery saves the innocent boy Teddy from a fatal snake bite.

“Snakes loomed large in the imperial imagination. Kipling’s story is typical of how snakes were typecast as villains in Victorian fiction. The cobras embody recurrent fears about the invasion of the supposedly hostile Indian environment into domestic spaces,” says Hall. “Snakes in India actually harmed very few Europeans, but when new statistical data revealed something of the extent of indigenous deaths due to snake bite, the problem became a challenge for a benevolent science as part of the rhetoric of the ‘civilising mission’.”

Humans and other primates are believed to have evolved an instinctive revulsion for snakes. This innate fear is reinforced by key narratives in the Bible, which remained a key authority on animals in the 19th century. In the creation story, the serpent wreaks havoc in the Garden of Eden by craftily tempting Eve to eat an apple from the Tree of Knowledge. Among the hundreds of pictorial representations of this story is German artist Johann König’s painting, Adam and Eve in Paradise (circa 1629), in the Fitzwilliam Museum.

“König’s snake shows some similarity to a European viper or adder. In such scenes the serpent is often seen coiled around the tree, watching on. Earlier depictions sometimes show the serpent in a more humanoid form, with a head, torso and upper limbs.

"The original physical form of the serpent in the Garden was a source of debate given that it was only afterwards cursed by God to crawl on its belly,” says Hall.

“The poor biblical reputation of snakes contributed to their unpopularity as objects of scientific study. But there were also practical obstacles to snake science relating to the collection, transportation, and preservation of snakes. Research into the effects of venom involved carrying out technically difficult and controversial experiments.”

From the 1820s, living snakes were collected to exhibit in newly-opened zoos in Britain. They had earlier appeared in travelling menageries. Snake specimens in alcohol, snakeskins and prepared skeletons had been mainstays of natural history collections from much earlier, but the number of species increased dramatically with imperial expansion in the 19th century.

At the Zoological Society’s gardens in Regent’s Park in London, visitors had the opportunity to see venomous snakes face-to-face at the new reptile house, which opened in 1849. Thousands flocked to see the snakes, including men of science such as Charles Darwin, who took the opportunity to carry out research into animal emotions.

The reptile house was conceived and marketed as an educational resource, but many people visited it for the thrill of seeing (and provoking) dangerous snakes up close, and ended up confirming their own preconceived ideas. Tragedy struck in 1852 when a keeper of reptiles, Edward Gurling, was bitten on the nose by a cobra and killed. The Zoological Society moved quickly to reassure the public of the safety of the establishment, and the keeper was described as being drunk from a night of gin drinking and acting with “rashness and indiscretion”.

“The death of Gurling was an important moment for scientific research into venomous snakes,” says Hall. “It led to an upsurge in interest in venomous snakes and renewed efforts to find an antidote to their venom in the colonies. Correspondents wrote to The Times offering up their own treatments for snake bite guaranteed by time spent in Africa and on the subcontinent. But it would be another four decades before the first anti-venom was developed.”

Next in the Cambridge Animal Alphabet: W is for an animal that made the journey from a beach in Sussex, to pride of place in the Museum of Zoology.

Have you missed the series so far? Catch up on Medium here.

Inset images: Aboriginal painting of the prothrombinase complex (Tom Murray-Rust); Adam and Eve in Paradise by Johann König (Fitzwilliam Museum); Detail from Adam and Eve in Paradise by Johann König (Fitzwilliam Museum); Illustration of the Zoological Society’s reptile house (Illustrated London News, 2 June 1849).

The Cambridge Animal Alphabet series celebrates Cambridge's connections with animals through literature, art, science and society. Here, V is for Venomous Snake: an animal that has long evoked fear and curiosity, but is revealing important clues for the development of treatments for some devastating conditions.

Weaponising is the term used describe the way in which snakes convert a substance into venom – without poisoning themselves
Jim Huntington
Skull of Bitus arietans – or Puff Adder – from the family Viperidae

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Phone for a doctor

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It’s the middle of the afternoon. You hear the trill of an incoming text message on your phone. You pick it up, expecting 
it to be from a friend.

Skipping breakfast will make you overeat at lunch.

Ah yes, this must be from Professor Ambady Ramachandran. You’ve never met him and he doesn’t know you personally, but he has sent you this helpful reminder because you are one of over 20 million Indians at a high risk of developing type 2 diabetes. Tomorrow, you tell yourself, you will make sure you eat before going to work.

“It seems paradoxical that something as simple as text messaging could help prevent you from developing diabetes,” says Professor Nick Wareham, Director of the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge. And yet, the evidence suggests it might work.

In 2013, Ramachandran, who founded and runs a diabetes hospital in Chennai, India, and is President of the India Diabetes Research Foundation, reported the results of a study that found almost a third fewer men in the high risk group went on to develop diabetes if they received between two and four texts a week giving advice on diet and exercise.

“This is a big – and surprising – effect,” says Wareham. And India, as with many other countries worldwide, needs something big (and, possibly, surprising) to help it tackle the growing burden of diabetes and obesity. Recent estimates suggest there are 68 million people living with diabetes in India, the majority with type 2 diabetes. A mixture of poor diet and lack of exercise, low birth weight followed by rapid growth, and genetic predisposition – Indians tend to develop diabetes at a lower body-mass index than Caucasians – means that diabetes is twice as common in India as it is in the UK.

While targeted strategies aimed at high risk individuals are likely to be effective, there is no way they could be rolled out to 20 million people, says Wareham. “If you had to individually counsel that many people, it would be unaffordable. Simple, pragmatic, scalable approaches are the only ones that are feasible.”

Ramachandran’s study involved a relatively small sample, but such was its promise that he and Wareham have teamed up to see whether text messaging might be scaled up to a larger population, with support from the MRC and the Indian Council for Medical Research. An additional arm of the study, being carried out by Imperial College London, is looking at whether the same concept would work in the UK.

Wareham and colleagues use a combination of a risk score that they 
have developed, which looks at factors such as age, sex and weight, and a simple blood test to identify people at 
risk of developing diabetes: these are 
the individuals who are targeted by the text messages.

It is the pervasiveness of mobile phones that could make this scheme work: there are almost a billion mobile phones in India – the country ranks second only to China. Smartphones are still much less common, with just around one in six people in the country owning one, but this is expected to increase significantly, potentially making India the second largest market worldwide.

If, as expected, smartphones really do take off, they could hold the answer to helping those people unfortunate enough to develop diabetes to monitor their condition, says Chris Lowe, Emeritus Professor of Biotechnology at the Department of Chemical Engineering and
 Biotechnology in Cambridge.

“We’re interested in developing diagnostics that are appropriate for taking measurements at home or in the doctor’s surgery, without the need for a specialist,” says Lowe. For over a decade, he has been looking at making ‘smart’ holograms that are sensitive to chemicals or biological compounds.

Unlike conventional holograms, which are two-dimensional, Lowe’s holograms are three-dimensional, created by shining a one-nanosecond laser pulse into a gel, suspended in which are silver nanoparticles. The silver nanoparticles arrange themselves into planes, giving the hologram a particular colour. But when glucose – from a blood or urine sample – comes into contact with the hologram, it binds to sensors within the gel, known as receptors, causing the hologram to expand or contract; the planes move closer together or further apart and the light given off by the hologram changes colour, moving towards the blue or red end of the spectrum.

“You can see these changes visually, but to increase the accuracy you need to be able to quantify the change, and this is where smartphones come in,” he says. Using the phone’s camera and a downloadable app, it could be possible to give an accurate measurement of the level of glucose in the body. His colleague Dr Gita Khalili Moghaddam 
is working on software that would enable the app to operate in a real-world setting, compensating for variability between phones and the environment.

The technology works in a similar way to QR codes – the black-and-white square patterns which, when scanned on a phone, redirect you to information online. In fact, says Moghaddam, the holograms could themselves be QR codes. “You can save the patient’s information in the holographic QR code, so when you scan it and send off your glucose levels, embedded in this are your own details,” she says.

Lowe and colleagues are exploring ways of delivering the holograms, from strips of holograms through to contact lenses that measure glucose in tear fluid as a surrogate for blood sugar levels, and even to having holograms that can be tattooed onto skin. These could even do away with the need to take regular blood finger-prick tests.

Despite the hi-tech nature of this technology, part of its beauty lies in its cost. The holograms could be mass-produced at a very low cost – even if they were embedded into daily-use contact lenses, the cost would be negligible, making them particularly attractive in the developing world. At the moment, patients need special instruments to monitor their glucose levels – in areas such as rural India, these are often given away, but their cost then has to be incorporated into the disposable strips used by the instruments.

“With smart holograms, there is no instrument,” says Lowe. “It’s just your smartphone. And soon, almost everyone will have one of those.”

Worried you might be at risk from diabetes? Check your phone: it might help stop 
you getting the disease. And if you already have diabetes? Your phone might even help you monitor your condition at home.

With smart holograms, there is no instrument. It’s just your smartphone. And soon, almost everyone will have one of those
Chris Lowe
mobile-mobile

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Yes
License type: 

Can the EU keep the peace in Europe? Not a chance

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The European Union won the Nobel Peace Prize in 2012 because of its “six decade-long contribution to peace and human rights in Europe”. In 2015, as the UK gears up towards its referendum on EU membership, we hear very often that the EU played a key role in building peace after World War II. For all its faults, the argument goes, the European Union is the best peace project Europe has.

There are three reasons why this is wrong. The first is that European integration contributed very little to the building of peace in post-war Europe. The second is that the EU’s record in keeping the peace on its external borders is poor. The third is that the Euro has aggravated conflicts between the members of the Eurozone: between north and south, creditor and debtor, exporter and importer.

It may seem crazy to suggest that the EU is not a peace project. This is, after all, its founding narrative. But history suggests otherwise for two reasons.

One is that in the late 1940s and 1950s there were many more powerful forces leading to peace in Europe. The shift from warfare to welfare states, made possible by the class compromise put in place after World War II, was crucial. European cooperation was really just an extension of that deeper change in European societies. The Common Agricultural Policy (CAP) was intended to extend welfare provision to farmers.

Central to post-war peace in Europe was also the Cold War and the support given to Western Europe by the United States. Most important of all was the post-war boom. After the war, people wanted a better life and it was to their own governments that they turned.

Another reason is that the EU of today has little to do with European cooperation in the 1950s. Today’s EU has more recent roots. The Coal and Steel Community was a cartel intended to make European steel production more competitive and give the French access to West German coal. This initiative was quickly overcome by the economic success that raised demand for coal and steel. By 1957, it was quietly folded into the Treaty of Rome.

The aim of the Treaty of Rome was to soften the effects of economic success. Growing economies push up wages and prices, which makes imports cheaper and leads to repeated balance of payments problems. Look at Britain’s Stop-Go economic experience of the 1950s and 1960s. A common external tariff, which raised the prices of imports, was Western Europe’s answer to this problem.

Today’s EU has its roots in economic crisis, not in economic success. Its history takes us back to the 1970s and the end of the post-war consensus. Governments sought many ways to exit this crisis and eventually settled on European market integration (the Single European Act) plus fiscal consolidation through more robust external rules (the Maastricht Treaty). This takes us to the EU and the euro of today.

Groundhog Europe

The European Union has not been very successful at promoting peace beyond its own borders. The EU does have a foreign policy but it is stuck in a time loop.

If one goes back 20 years to 1995, the kinds of questions being raised about Europe’s role in promoting peace related to whether it would speak with one voice. This was the time of the Yugoslav war when European divisions meant that the United States got heavily involved in the Balkans. People wondered if the EU would finally become not just an economic giant but a political one, too. People described 1995 as a crossroads and a watershed moment.

Fast forward to 2005 and the very same clichés are being used. Two years after the US invasion of Iraq had divided Europe, people asked when it would speak with one voice. The EU was again at a crossroads. This was two years after the EU’s first Security Strategy, intended to give Europe a sense of direction in foreign policy.

Today, we hear much the same thing and Europeans are once again drafting a new security strategy. The war in Ukraine led commentators to lament the divisions between EU member states. The rise of Islamic State in the Middle East has made people wonder if the EU will ever become a regional power or whether it will always have a “lowest common denominator” foreign policy.

As in the film Groundhog Day, where Bill Murray is stuck in a time loop, the European Union is forced to relive its foreign policy frustrations time and time again. Groundhog Day has a Hollywood-style happy ending; the EU may not be so lucky.

The euro versus democracy

The euro was meant to lead to convergence in Europe. It was expected that a single currency would lead to harmonisation of national business cycles. Instead, the buzzword amongst economists is heterogeneity.

The euro has created new divisions but it has also cemented older ones. It has exaggerated the differences between productive and unproductive national economies. It has heightened intra-Eurozone competition. New divisions between debtors and creditors have broken out. There is no single European economy, just very different national economies. More than ever before, the economic map of Europe looks like it did in the 19th century when advanced northern societies complained about the “backwardness” of southern and eastern Europe.

A solution to this is to build a political union with fiscal powers. Transfers from rich to poor parts of Europe would iron out today’s enormous gaps. There is no political appetite for this anywhere, neither among elites nor among domestic publics. As a result, the survival of the Eurozone seems set against national democracy. Few accept this at present but the euro and national democracy may be incompatible.

We are right to ask if Europe can keep the peace. The answer is “no”. Peace in Europe owes much to other factors and the EU has done little to build peace beyond its borders. Peace within Europe has become fragile as the euro unleashes competitive pressures that pit national economies against one another.

Chris Bickerton, Lecturer in politics at POLIS, University of Cambridge

This article was originally published on The Conversation. Read the original article.

Inset image: Marcha en Madrid en solidaridad con Grecia y por el NO (OXI) en el referéndum griego (Adolfo Lujan).

The opinions expressed in this article are those of the individual author(s) and do not represent the views of the University of Cambridge.

Chris Bickerton (Department of Politics and International Relations) discusses the role of the European Union.

European Commission

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Spiritual violence and the divine revolution of Sri Aurobindo Ghosh

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By the time he had moved back to Calcutta in 1906, the state had been split in half by Lord Curzon, Viceroy of India. The British claimed this schism was ‘administrative’, but it was largely an attempt to quell burgeoning political dissent in the region. 

The partitioning of Bengal – a prime example of British ‘divide and rule’ policy – incensed many sections of the population, and the Indian ‘middle classes’ mobilised under the banner of Swadeshi, the anti-imperial resistance movement that would eventually force the British to revoke the partition six years later.

While ‘moderate’ Indian leaders lobbied the British for greater representation, many of the younger generation in Bengal – particularly Hindus – believed that ‘prayer, petition and protest’ would fail, and more radical action was needed: non-cooperation, law-breaking and even violence, in the name of ‘Swaraj’ – self-rule. One of the figureheads of ‘extremist’ Swadeshi was Aurobindo, a teacher, poet, polemical journalist and underground revolutionary leader.

In his later years, Aurobindo became one of India’s most influential international Gurus, redefining Hinduism for the modern age with his experimental mysticism (Integral Yoga), global outlook and life-affirming metaphysics of divine evolution. His philosophy is taught across India and was recognised early on by prominent Western figures including Aldous Huxley, who nominated him for a Nobel Peace Prize in 1950. He was also a major inspiration for the ‘New Age’ movement that swept across the West. 

Today, the popular perception of Aurobindo’s life is divided. The early political firebrand and later mystic are seen as separate identities, split by a year of imprisonment during which Aurobindo was spiritually ‘awakened’.

However, for Alex Wolfers, a researcher at Cambridge’s Faculty of Divinity, this dichotomy is a false one. The spiritual and political blurred throughout Aurobindo’s extraordinary life, particularly during his time as a leading light of radical Swadeshi, says Wolfers, who is investigating spirituality in Aurobindo’s early political writing.

Through research at archives in Delhi, Kolkata and Aurobindo’s Ashram in Pondicherry, Wolfers has traced the emergence of a new theology of revolution in Aurobindo’s thoughts, one that harnessed the spiritual to challenge “the sordid interests of British capital”.

Aurobindo fused the political and spiritual, mixing ideas from European philosophy, particularly Hegel and Nietzsche, with Hindu theology under the aegis of the Tantric mother goddess, Kali, and Bengali Shaktism – the worship of latent creative energy – to develop a radical political discourse of embodied spirituality, heroic sacrifice and transformative violence.

He complemented this with poetic interpretations of the French revolution and Ireland’s growing Celtic anti-imperialism, as well as contemporary upheavals in Russia, South Africa and Japan.

Through his polemical speeches and essays, Aurobindo furiously developed his political theology against a backdrop of assassination, robbery and bombings, weaving all of these strands into what Wolfers argues is the central symbolic archetype in his political theology: the ‘revolutionary Sannyasi’.

In Hindu philosophy, Sannyasis are religious ascetics – holy men who renounce society and worldly desires for an itinerant life of internal reflection and sacrifice. Throughout the late 18th century in famine-stricken Bengal, roving bands of Sannyasis – together with their Muslim counterparts, Fakirs – challenged the oppressive tax regime of the British, and repeatedly incited the starving peasants to rebel.

Aurobindo amplified and weaponised this already potent symbolic figure by recasting him as a channel for divine violence. By embodying Swaraj, the revolutionary Sannyasi could kill with sanctity. Violent revolution became spiritually transcendent, without murderous stain.

“Just as the traditional Sannyasi intensifies his inner divinity through ascetic practice or the voluntary embrace of suffering, Aurobindo venerates the element of violence and adversity in existence as a prelude to collective ‘self-overcoming’,” says Wolfers.

As Wolfers puts it, the revolutionary Sannyasi is the man of spirit and action, sanctified by sacrifice, whose volatile potency is ready to detonate like a bomb in a violent spectacle of Liebestod: the ‘love-death’ of German romanticism, the ecstatic destruction needed for rebirth. As Aurobindo himself states, “war is the law of creation”.

“This violent vanguardism is often seen as an infantile politics that limits broader participation in a political movement,” says Wolfers, “but even the non-violent Gandhi significantly borrowed from Aurobindo’s transgressive politics. This form of terrorism was crucial in implanting the radical ideals of Swaraj that later anti-imperialist politics were structured around.”

Aurobindo’s highly Anglicised, elite Cambridge education had left him estranged from his roots. On his return to India in 1893, he had to ‘re-learn his identity’ through classical Hindu texts, whereas his younger brother Barin, who had grown up closer to home, was more familiar with the living traditions of Bengal.

Together, Aurobindo, the prophetic visionary, and Barin, the untiring activist, organised the spread of a loose network of underground terrorist cells throughout the land and incited the increasingly politicised student communities of Bengal to submit themselves to the militant spirituality of the ‘revolutionary Sannyasi’.

“These young revolutionaries took their cues from Aurobindo’s discourses of Sannyasi renunciation: they left their families and society, living rigorously according to rituals and timetables, dressing in the traditional ochre robes of the Sannyasi. Some even made use of Tantric practices, carrying out blood rites and secret vows in cremation grounds to purify their life in contact with death,” says Wolfers. “Through these practices they cast off their allocated ‘middle classness’, breaking free from imposed British society.”

The revolutionaries targeted figures of British state authority and, in May 1908, Aurobindo was arrested in connection with the botched assassination attempt of a notorious magistrate. It was while in solitary confinement in Alipore jail that he experienced the ‘spiritual awakening’ that confirmed his mystic status.

Over 60 years after his death in 1950, Aurobindo’s legacy continues to live on, despite often being misappropriated 
for political gain.

“The figure of the ‘revolutionary Sannyasi’ has had an enormous afterlife: in its various guises and mutations, its influence is evident across the political spectrum from Gandhian mobilisation to Bengali Marxism and Hindu nationalism. Even today, it remains an important trope in Indian politics,” says Wolfers. 

“From as early as the 1920s, Hindu nationalist organisations began to recast Aurobindo in an increasingly right-wing mould to assert Hindu dominance against the subcontinent’s Muslim and Christian minorities,” he says. “But hyper-masculine Hindu chauvinism, still a major force in Indian politics today, stands in sharp contrast with his original inclusive and ‘anarchic’ outlook.”

In 1879, a young Indian boy arrived in England from Calcutta (now Kolkata), in the state of Bengal, sent by his father to receive a British education. Aurobindo Ghosh showed enormous promise and would go on to receive a scholarship to study classics at King’s College, Cambridge.

Even the non-violent Gandhi significantly borrowed from Aurobindo’s transgressive politics
Alex Wolfers
Sri Aurobindo Ghosh

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New design points a path to the ‘ultimate’ battery

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Scientists have developed a working laboratory demonstrator of a lithium-oxygen battery which has very high energy density, is more than 90% efficient, and, to date, can be recharged more than 2000 times, showing how several of the problems holding back the development of these devices could be solved.

Lithium-oxygen, or lithium-air, batteries have been touted as the ‘ultimate’ battery due to their theoretical energy density, which is ten times that of a lithium-ion battery. Such a high energy density would be comparable to that of gasoline – and would enable an electric car with a battery that is a fifth the cost and a fifth the weight of those currently on the market to drive from London to Edinburgh on a single charge.

However, as is the case with other next-generation batteries, there are several practical challenges that need to be addressed before lithium-air batteries become a viable alternative to gasoline.

Now, researchers from the University of Cambridge have demonstrated how some of these obstacles may be overcome, and developed a lab-based demonstrator of a lithium-oxygen battery which has higher capacity, increased energy efficiency and improved stability over previous attempts.

Their demonstrator relies on a highly porous, ‘fluffy’ carbon electrode made from graphene (comprising one-atom-thick sheets of carbon atoms), and additives that alter the chemical reactions at work in the battery, making it more stable and more efficient. While the results, reported in the journal Science, are promising, the researchers caution that a practical lithium-air battery still remains at least a decade away.

“What we’ve achieved is a significant advance for this technology and suggests whole new areas for research – we haven’t solved all the problems inherent to this chemistry, but our results do show routes forward towards a practical device,” said Professor Clare Grey of Cambridge’s Department of Chemistry, the paper’s senior author.

Many of the technologies we use every day have been getting smaller, faster and cheaper each year – with the notable exception of batteries. Apart from the possibility of a smartphone which lasts for days without needing to be charged, the challenges associated with making a better battery are holding back the widespread adoption of two major clean technologies: electric cars and grid-scale storage for solar power.

“In their simplest form, batteries are made of three components: a positive electrode, a negative electrode and an electrolyte,’’ said Dr Tao Liu, also from the Department of Chemistry, and the paper’s first author.

In the lithium-ion (Li-ion) batteries we use in our laptops and smartphones, the negative electrode is made of graphite (a form of carbon), the positive electrode is made of a metal oxide, such as lithium cobalt oxide, and the electrolyte is a lithium salt dissolved in an organic solvent. The action of the battery depends on the movement of lithium ions between the electrodes. Li-ion batteries are light, but their capacity deteriorates with age, and their relatively low energy densities mean that they need to be recharged frequently.

Over the past decade, researchers have been developing various alternatives to Li-ion batteries, and lithium-air batteries are considered the ultimate in next-generation energy storage, because of their extremely high energy density. However, previous attempts at working demonstrators have had low efficiency, poor rate performance, unwanted chemical reactions, and can only be cycled in pure oxygen.

What Liu, Grey and their colleagues have developed uses a very different chemistry than earlier attempts at a non-aqueous lithium-air battery, relying on lithium hydroxide (LiOH) instead of lithium peroxide (Li2O2). With the addition of water and the use of lithium iodide as a ‘mediator’, their battery showed far less of the chemical reactions which can cause cells to die, making it far more stable after multiple charge and discharge cycles.

By precisely engineering the structure of the electrode, changing it to a highly porous form of graphene, adding lithium iodide, and changing the chemical makeup of the electrolyte, the researchers were able to reduce the ‘voltage gap’ between charge and discharge to 0.2 volts. A small voltage gap equals a more efficient battery – previous versions of a lithium-air battery have only managed to get the gap down to 0.5 – 1.0 volts, whereas 0.2 volts is closer to that of a Li-ion battery, and equates to an energy efficiency of 93%.

The highly porous graphene electrode also greatly increases the capacity of the demonstrator, although only at certain rates of charge and discharge. Other issues that still have to be addressed include finding a way to protect the metal electrode so that it doesn’t form spindly lithium metal fibres known as dendrites, which can cause batteries to explode if they grow too much and short-circuit the battery.

Additionally, the demonstrator can only be cycled in pure oxygen, while the air around us also contains carbon dioxide, nitrogen and moisture, all of which are generally harmful to the metal electrode.

“There’s still a lot of work to do,” said Liu. “But what we’ve seen here suggests that there are ways to solve these problems – maybe we’ve just got to look at things a little differently.”

“While there are still plenty of fundamental studies that remain to be done, to iron out some of the mechanistic details, the current results are extremely exciting – we are still very much at the development stage, but we’ve shown that there are solutions to some of the tough problems associated with this technology,” said Grey.

The authors acknowledge support from the US Department of Energy, the Engineering and Physical Sciences Research Council (EPSRC), Johnson Matthey and the European Union via Marie Curie Actions and the Graphene Flagship. The technology has been patented and is being commercialised through Cambridge Enterprise, the University’s commercialisation arm. 

Reference:
Liu, T et. al. ‘Cycling Li-O2 Batteries via LiOH Formation and Decomposition.’ Science (2015). DOI: 10.1126/science.aac7730

Researchers have successfully demonstrated how several of the problems impeding the practical development of the so-called ‘ultimate’ battery could be overcome.

What we’ve achieved is a significant advance for this technology and suggests whole new areas for research
Clare Grey
False-colour microscopic view of a reduced graphene oxide electrode (black, centre), which hosts the large (on the order of 20 micrometers) lithium hydroxide particles (pink) that form when a lithium-oxygen battery discharges.

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Breaking the mould: Untangling the jelly-like properties of diseased proteins

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A common characteristic of neurodegenerative diseases – such as Alzheimer’s, Parkinson’s and Huntington’s disease – is the build-up of ‘misfolded’ proteins, which cause irreversible damage to the brain. For example, Alzheimer’s disease sees the build-up of beta-amyloid ‘plaques’ and tau ‘tangles’.

In the case of some forms of motor neurone disease (also known as amyotrophic lateral sclerosis, or ALS) and frontotemporal dementia, it is the build up of ‘assemblies’ of misshapen FUS protein and several other RNA-binding proteins that is associated with disease. However, the assembly of these RNA binding proteins has several differences to conventional protein aggregates seen in Alzheimer’s disease and Parkinson’s disease and as a result, the significance of the build-up of these proteins and how it occurs has until now been unclear.

FUS is an RNA-binding protein, which has a number of important functions in regulating RNA transcription (the first step in DNA expression) and splicing in the nucleus of cells. FUS also has functions in the cytoplasm of cells involved in regulating the translation of RNA into proteins. There are several other similar RNA binding proteins: a common feature of all of them is that in addition to having domains to bind RNA they also have domains where the protein appears to be unfolded or unstructured.

In a study published today in the journal Neuron, scientists at the University of Cambridge examined FUS’s physical properties to demonstrate how the protein’s unfolded domain enables it to undergo reversible ‘phase transitions’. In other words, it can change back and forth from a fully soluble ‘monomer’ form into distinct localised accumulations that resemble liquid droplets and then further condense into jelly-like structures that are known as hydrogels. During these changes, the protein ‘assemblies’ capture and release RNA and other proteins. In essence this process allows cellular machinery for RNA transcription and translation to be condensed in high concentrations within restricted three-dimensional space without requiring a limiting membrane, thereby helping to easily regulate these vital cellular processes.

Using the nematode worm C. elegans as a model of ALS and frontotemporal dementia, the team was then able to also show that this process can become irreversible. Mutated FUS proteins cause the condensation process to go too far, forming thick gels that are unable to return to their soluble state. As a result, these irreversible gel-like assemblies trap other important proteins, preventing them carrying out their usual functions. One consequence is that it affects the synthesis of new proteins in nerve cell axons (the trunk of a nerve cell).

Importantly, the researchers also showed that by disrupting the formation of these irreversible assemblies (for example, by targeting with particular small molecules), it is possible to rescue the impaired motility and prolong the worm’s lifespan.

Like jelly on a plate

The behaviour of FUS can be likened to that of a jelly, explains Professor Peter St George Hyslop from the Cambridge Institute for Medical Research.

When first made, jelly is runny, like a liquid. As it cools the fridge, it begins to set, initially becoming slightly thicker than water, but still runny as the gelatin molecules forms into longer, fibre-like chains known as fibrils. If you dropped a droplet of this nearly-set jelly into water, it would (at least briefly) remain distinct from the surrounding water – a ‘liquid droplet’ within a liquid.

As the jelly cools further in the fridge, the gelatin fibres condense more, and it eventually becomes a firmly set jelly that can be flipped out of the mould onto a plate. This set jelly is a ‘hydrogel’, a loose meshwork of protein (gelatin) fibrils that is dense enough to hold the water inside the spaces between its fibres. The set jelly holds the water in a constrained 3D space – and depending on the recipe, there may be some other ‘cargo’ suspended within the jelly, such as bits of fruit (in the case of FUS this ‘cargo’ might be ribosomes, other proteins, enzymes or RNA, for example).

When the jelly is stored in a cool room, the fruit is retained in the jelly. This means the fruit (or ribosomes, etc) can be moved around the house and eventually put on the dinner table (or in the case of FUS, be transported to parts of a cell with unique protein synthesis requirements).

If the jelly is re-warmed, it melts and releases its fruit, which then float off‎. But if the liquid molten jelly is put back in the fridge and re-cooled, it re-makes a firm hydrogel again, and the fruit is once again trapped. In theory, this cycle of gel-melt-gel-melt can be repeated endlessly.

However, if the jelly is left out, the water will slowly evaporate, and the jelly condenses down, changing from a soft, easily-melted jelly to a thick, rubbery jelly.  (In fact, jelly is often sold as a dense cube like this.) In this condensed jelly, the meshwork of protein fibrils are much closer together and it becomes increasingly difficult to get the condensed jelly to melt (you would have to pour boiling water on it to get it to melt). Because the condensed jelly is not easily meltable when it gets to this state, any cargo (fruit, ribosomes, etc.) within the jelly essentially becomes irreversibly trapped.

In the case of FUS and other RNA binding proteins, the ‘healthy’ proteins only very rarely spontaneously over-condense. However, disease-causing mutations make these proteins much more prone to spontaneously ‎condense down into thick fibrous gels, trapping their cargo (in this case the ribosomes, etc), which then become unavailable for use.

So essentially, this new research shows that the ability of some proteins to self-assemble into liquid droplets and (slightly more viscous) jellies/hydrogel is a useful property that allows cells to transiently concentrate cellular machinery into a constrained 3D space in order to perform key tasks, and then disassemble and disperse the machinery when not needed. It is probably faster and less energy-costly than doing the same thing inside intracellular membrane-bound vesicles – but that same property can go too far, leading to disease.

Professor St George Hyslop says: “We’ve shown that a particular group of proteins can regulate vital cellular processes by their distinct ability to transition between different states. But this essential property also makes them vulnerable to forming more fixed structures if mutated, disrupting their normal function and causing disease.

“The same principles are likely to be at play in other more common forms of these diseases due to mutation in other related binding proteins. Understanding what is in these assemblies should provide further targets for disease treatments.

“Our approach shows the importance of considering the mechanisms of diseases as not just biological, but also physical processes. By bringing together people from the biological and physical sciences, we’ve been able to better understand how misshapen proteins build up and cause disease.”

The research was funded by in the UK by the Wellcome Trust, Medical Research Council and National Institutes of Health Research, in Canada by Canadian Institutes of Health Research, and in the US by National Institutes of Health.

Reference
Murakami, T et al. ALS/FTD mutation-induced phase transition of FUS liquid droplets and reversible hydrogels into irreversible hydrogels impairs RNP granule function. Neuron; 29 Oct 2015

Scientists at the University of Cambridge have identified a new property of essential proteins which, when it malfunctions, can cause the build up, or ‘aggregation’, of misshaped proteins and lead to serious diseases.

Our approach shows the importance of considering the mechanisms of diseases as not just biological, but also physical processes
Peter St George-Hyslop
Jello Cubes

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